ANTITUMORALI

Il cancro egrave una crescita incontrollata di cellule spesso con comportamento

maligno invasivo e metastatico Si pensa che il cancro sia causato da

unrsquointerazione tra la suscettibilitagrave genetica dellrsquoindividuo e tossine ambientali

Generalmente la maggior parte dei chemioterapici agiscono inibendo la mitosi

cellulare coinvolgendo perciograve cellule in veloce riproduzione Questi farmaci sono

perciograve chiamati citotossici Alcuni chemioterapici causano lrsquoapoptosi cellulare

Gli effetti degli antitumorali sono perciograve anche su cellule non tumorali ed impediscono perciograve la crescita dei peli (capelli) e dellrsquoepitelio intestinale

I tumori ad alto frazione di crescita come la leucemia mieloide acuta linfomi di Hodgkinrsquos sono i piugrave sensibili ai chemioterapici

Un problema dei chemioterapici egrave nei confronti dei tumori solidi in quanto non riescono a raggiungere il centro del tumore Soluzioni a questo problema sono la radioterapia o la chirurgia

Una terapia combinata tra chemioterapia e radioterapia egrave una soluzione al problema

La terapia adiuvante detta anche chemioterapia pre e post -chirurgica ha lo scopo di ridurre la massa tumorale prima dellrsquointervento rendendo cosigrave la terapia locale (chirurgia e radioterapia) meno distruttiva e piugrave efficacePer chemioterapia palliativa si intende quella cura che ha lo scopo di ridurre la massa tumorale aumentando lrsquoaspettativa di vita

CLASSI DI FARMACI ANTITUMORALI

1) Agenti alchilanti

2) Antimetaboliti

3) Antimitotici

4) Alcaloidi di origine vegetale

5) Antibiotici antitumorali

6) Inibitori Topoisomerasi

7) Anticorpi monoclonali

8) Inibitori dei fattori di crescita

AGENTI ALCHILANTI

A) Alchil sulfonati (busulfano)

B) Nitrosouree (Carmustina Lomustina)

C) Mostarde azotate ( Ciclofosfamide Mecloretamina uramustina

Melphalan clorambucile ifosfamide)

D) Composti del Platino (Cis-platino Carboplatino Oxaliplatino)

E) Idrazine (Procarbazina)

F) Tiazine (Dacarbazina)

G) Aziridine (Tiotepa)

Nitrosuree

1) Carmustina2) Streptozocina

Imidazotetrazine

Temozolimide

Lomustina

Mostarde azotate

Cyclophosphamide

Mecloretamina

Melphalan Clorambucile

Composti antitumorali del platino

1) Cisplatino

2) Carboplatino

3) Oxaliplatino

4) Tetranitrato triplatino

Idrazine

Procarbazina

Tiazine

Dacarbazina Tiotepa

Aziridine

La dacarbazina egrave un agente alchilante usata nel melanoma maligno nel linfoma di Hodgkin nei sarcomi e nei carcinomi del pancreas

Meccanismo di azione degli agenti alchilanti

Gli agenti alchilanti si legano con molte molecole intracellulari tra cui gli acidi

nucleici impedendone la lettura e quindi la trascrizione La citotossicitagrave egrave

primariamente dovuta al legame crociato tra filamenti di DNA ed RNA cosigrave

come allrsquoinibizione della sintesi proteica

Il busulfano egrave il solo agente usato nei regimi di mielosoppressione nei trapianti di cellule staminali ematopoietiche per la quale il monitoraggio terapeutico del farmaco egrave largamente usato Lrsquouso di busulfano per via orale porta ad una grande variabilitagrave intrapaziente e interpaziente in termini farmacocinetici specialmente nei bambini e lrsquoaggiustamento delle dosi egrave necessario per una ridotta tossicitagrave e migliore riuscita terapeutica Lrsquouso di busulfano per via endovenosa sta prendendo piede in quando porta a dei profili farmacocinetici piugrave controllabili La meningite neoplasica rappresenta il 5 dei tumori Ersquo una malattia che colpisce lrsquointero neuroasse e i farmaci devono passare nel fluido cefalorachidiano Oggigiorno la terapia con farmaci direttamente immessi nel liquido cefalorachidiano egrave ristretta a tre farmaci Il metotressato la citarabina ed il tiotepa Il cis-platino egrave un antitumorale usato per trattare vari tipi di cancro tipo sarcoma carcinosarcomi (piccolo cellule del polmone cancro ovarico) linfomi Ersquo il primo di una classe che va in crescendo di nuovi composti quali il carboplatino lrsquooxaliplatino Questi composti formano dei complessi allrsquointerno della cellula tumorale i quali legano il DNA attraverso legami intracatena e tra catene di DNA A questo segue lrsquoapoptosi cellulare

Although the entity we refer today as chronic myeloid leukemia (CML) was probably first described in the early nineteenth century there was little progress in understanding its biology until the discovery of the Philadelphia (Ph) chromosome in 19601 Subsequent important landmarks were the recognition that the Ph chromosome results from a t(922) translocation the demonstration that the leukemia probably originates from a single hematopoietic ldquostem cellrdquo the identification of the breakpoint cluster region (BCR) on chromosome no 22 and subsequently of the BCR-ABL fusion gene and more recently thedevelopment of a murine model simulating the human disease23 Treatment in the 19th century was unsatisfactory although arsenicals induced some degree of symptomatic control In the early 20th century radiotherapy was helpful but it was replaced in the 1950s by busulfan which remained popular for some years despite the emerging suspicion that this alkylating agent might in fact predispose to progression to advanced-phase disease In due course hydroxycarbamide replaced busulfan but interferon-alfa the first agent to induce any degree of Ph-chromosome negativity in the bone marrow was introduced in the early 1980s and became the treatment of choice for patients not eligible for allogeneic stem cell transplantation Between 1980 and 2000 allografting despite the risks of morbidity and mortality was the recommended initial treatment for younger patients with HLA-matched donors Therapy has now been ldquorevolutionizedrdquo by the introduction of imatinib (imatinib mesylate IM) the original Abl tyrosine kinase inhibitor (TKI) which was used first in the clinic in 1998

(Blood 20071102828-2837)

Lrsquoosteosarcoma egrave un cancro a carico dellrsquoosso e generalmente colpisce le ossa grandi delle braccia e delle gambe Ersquo presente frequentemente in giovani e sopratutto nei maschi La prognosi dellrsquo osteosarcoma degli arti trattata con solo amputazione puograve essere migliorata drammaticamente includendo la chemioterapia La chemioterapia neoadiuvante egrave comunemente usata per eradicare le micrometastasi e per preparare gli arti alla chirurgia di salvataggioOggi giorno una chirurgia conservativa egrave possibile nella maggior parte dei pazienti incluso i bambini ed egrave anche libera da recidive nei casi di sopravvivenza nel 50-80 Alte dosi di metotressato doxorubicina cis-platino ed ifosfamide sono considerate i

farmaci piugrave attivi contro lrsquoosteosarcoma Bull Cancer 2006 Nov 193(11)1115-20

Definizione del linfoma di Hodgkin Un cancro del sistema immunitario nel quale si evidenzia la presenza di un tipo particolare di cellule dette Reed-Sternberg cell I due tipi principali di linfoma di Hodgkin sono il classico e il nodulare che rappresenta il principale I sintomi includono dolore e ingrossamento dei linfonodi della milza o altri tessuti immunitari Altri sintomi includono febbre perdita di peso fatica e sudorazione notturna

Definizione di linfoma non-Hodgkin Rappresenta una versione di cancro al sistema immunitario (linfociti) Il linfoma non-Hodgkin egrave presente a qualsiasi etagrave e spesso egrave caratterizzato da ingrossamento dei linfonodi febbre e perdita di peso Ci sono diversi tipi di linfoma non-Hodgkin i quali possono essere suddivisi in aggressive (a crescita veloce) e indolenti ( a crescita lenta e possono essere classificati in linfomi delle cellule B o delle cellule T Tra i linfomi delle cellule B ricordiamo il linfoma di Burkitt linfomi diffusi delle cellule B linfomi follicolari linfomi immunoblastici a cellule grandi linfomi di precursori delle cellule B e linfomi di cellule mantello Linfomi non-Hodgkin delle cellule T includono micosi funginee linfomi anaplastici a cellule grandi e linfomi di precursori delle cellule T Linfomi correlati a disordini linfoproliferativi presenti a seguito di trapianti di midollo osseo o di cellule staminali generalmente sono linfomi non-hodgkin di cellule B

Reed-Sternberg cell

ANTIMETABOLITI

1) Analoghi dellrsquoacido folico

2) Analoghi delle purine

3) Analoghi delle pirimidine

Analoghi dellrsquoacido folico

Analoghi dellrsquoacido folico

METOTREXATOIl metotrexato egrave un analogo dellrsquoacido folico e inibisce la diidrofolico reduttasi prevenendo la formazione dellrsquoacido

tetraidrofolico Questo acido egrave essenziale per la formazione delle purine e pirimidine componenti del DNA ed RNA Il

tetraidofolato egrave coinvolto anche nella sintesi di aminoacidi quali serina e metionina

La sua tossicitagrave egrave a carico di cellule ad alta velocitagrave di duplicazione quali quelle del midollo della pelle e dei capelli

Leuk Lymphoma 2011 Oct52(10)1882-90 Epub 2011 Jun 12High-dose methotrexate based chemotherapy with deferred radiation for treatment of newly diagnosed primary central nervous system lymphomaGerard LM Imrie KR Mangel J Buckstein R Doherty M Mackenzie R Cheung MCOdette Cancer Centre Sunnybrook Health Sciences Centre Toronto Ontario CanadaAbstractThe addition of high-dose methotrexate (HD-MTX) to whole-brain radiation therapy (WBRT) has improved the survival of patients with primary central nervous system lymphoma (PCNSL) However combined therapy is associated with increased neurotoxicity In an effort to limit this toxicity we treated a series of non-immunocompromised patients with HDMVP a HD-MTX based regimen with deferral of WBRT until progression Twenty-three patients were treated with the HDMVP regimen consisting of MTX vincristine and procarbazine The mean age at diagnosis was 609 years (range 45-79 years) The overall response rate was 65 (14 complete responses and one partial response) For patients achieving an initial response with HDMVP the median response duration was 404 months (95 confidence interval [CI] 195-613) The median progression-free survival was 46 months (95 CI 00-204) and median overall survival was 414 months (95 CI 00-955) Fourteen patients received WBRT for relapsed or progressive disease The conclusion of this trial is that HDVMP results in good initial response rates but only moderate disease control Ultimately the majority of the patients in this series required WBRT for salvage treatment potentially enabling a delay in treatment-associated neurotoxicityPMID 21663504 [PubMed - in process]

Gli effetti degli antitumorali sono perciograve anche su cellule non tumorali ed impediscono perciograve la crescita dei peli (capelli) e dellrsquoepitelio intestinale

I tumori ad alto frazione di crescita come la leucemia mieloide acuta linfomi di Hodgkinrsquos sono i piugrave sensibili ai chemioterapici

Un problema dei chemioterapici egrave nei confronti dei tumori solidi in quanto non riescono a raggiungere il centro del tumore Soluzioni a questo problema sono la radioterapia o la chirurgia

Una terapia combinata tra chemioterapia e radioterapia egrave una soluzione al problema

La terapia adiuvante detta anche chemioterapia pre e post -chirurgica ha lo scopo di ridurre la massa tumorale prima dellrsquointervento rendendo cosigrave la terapia locale (chirurgia e radioterapia) meno distruttiva e piugrave efficacePer chemioterapia palliativa si intende quella cura che ha lo scopo di ridurre la massa tumorale aumentando lrsquoaspettativa di vita

CLASSI DI FARMACI ANTITUMORALI

1) Agenti alchilanti

2) Antimetaboliti

3) Antimitotici

4) Alcaloidi di origine vegetale

5) Antibiotici antitumorali

6) Inibitori Topoisomerasi

7) Anticorpi monoclonali

8) Inibitori dei fattori di crescita

AGENTI ALCHILANTI

A) Alchil sulfonati (busulfano)

B) Nitrosouree (Carmustina Lomustina)

C) Mostarde azotate ( Ciclofosfamide Mecloretamina uramustina

Melphalan clorambucile ifosfamide)

D) Composti del Platino (Cis-platino Carboplatino Oxaliplatino)

E) Idrazine (Procarbazina)

F) Tiazine (Dacarbazina)

G) Aziridine (Tiotepa)

Nitrosuree

1) Carmustina2) Streptozocina

Imidazotetrazine

Temozolimide

Lomustina

Mostarde azotate

Cyclophosphamide

Mecloretamina

Melphalan Clorambucile

Composti antitumorali del platino

1) Cisplatino

2) Carboplatino

3) Oxaliplatino

4) Tetranitrato triplatino

Idrazine

Procarbazina

Tiazine

Dacarbazina Tiotepa

Aziridine

La dacarbazina egrave un agente alchilante usata nel melanoma maligno nel linfoma di Hodgkin nei sarcomi e nei carcinomi del pancreas

Meccanismo di azione degli agenti alchilanti

Gli agenti alchilanti si legano con molte molecole intracellulari tra cui gli acidi

nucleici impedendone la lettura e quindi la trascrizione La citotossicitagrave egrave

primariamente dovuta al legame crociato tra filamenti di DNA ed RNA cosigrave

come allrsquoinibizione della sintesi proteica

Il busulfano egrave il solo agente usato nei regimi di mielosoppressione nei trapianti di cellule staminali ematopoietiche per la quale il monitoraggio terapeutico del farmaco egrave largamente usato Lrsquouso di busulfano per via orale porta ad una grande variabilitagrave intrapaziente e interpaziente in termini farmacocinetici specialmente nei bambini e lrsquoaggiustamento delle dosi egrave necessario per una ridotta tossicitagrave e migliore riuscita terapeutica Lrsquouso di busulfano per via endovenosa sta prendendo piede in quando porta a dei profili farmacocinetici piugrave controllabili La meningite neoplasica rappresenta il 5 dei tumori Ersquo una malattia che colpisce lrsquointero neuroasse e i farmaci devono passare nel fluido cefalorachidiano Oggigiorno la terapia con farmaci direttamente immessi nel liquido cefalorachidiano egrave ristretta a tre farmaci Il metotressato la citarabina ed il tiotepa Il cis-platino egrave un antitumorale usato per trattare vari tipi di cancro tipo sarcoma carcinosarcomi (piccolo cellule del polmone cancro ovarico) linfomi Ersquo il primo di una classe che va in crescendo di nuovi composti quali il carboplatino lrsquooxaliplatino Questi composti formano dei complessi allrsquointerno della cellula tumorale i quali legano il DNA attraverso legami intracatena e tra catene di DNA A questo segue lrsquoapoptosi cellulare

Although the entity we refer today as chronic myeloid leukemia (CML) was probably first described in the early nineteenth century there was little progress in understanding its biology until the discovery of the Philadelphia (Ph) chromosome in 19601 Subsequent important landmarks were the recognition that the Ph chromosome results from a t(922) translocation the demonstration that the leukemia probably originates from a single hematopoietic ldquostem cellrdquo the identification of the breakpoint cluster region (BCR) on chromosome no 22 and subsequently of the BCR-ABL fusion gene and more recently thedevelopment of a murine model simulating the human disease23 Treatment in the 19th century was unsatisfactory although arsenicals induced some degree of symptomatic control In the early 20th century radiotherapy was helpful but it was replaced in the 1950s by busulfan which remained popular for some years despite the emerging suspicion that this alkylating agent might in fact predispose to progression to advanced-phase disease In due course hydroxycarbamide replaced busulfan but interferon-alfa the first agent to induce any degree of Ph-chromosome negativity in the bone marrow was introduced in the early 1980s and became the treatment of choice for patients not eligible for allogeneic stem cell transplantation Between 1980 and 2000 allografting despite the risks of morbidity and mortality was the recommended initial treatment for younger patients with HLA-matched donors Therapy has now been ldquorevolutionizedrdquo by the introduction of imatinib (imatinib mesylate IM) the original Abl tyrosine kinase inhibitor (TKI) which was used first in the clinic in 1998

(Blood 20071102828-2837)

Lrsquoosteosarcoma egrave un cancro a carico dellrsquoosso e generalmente colpisce le ossa grandi delle braccia e delle gambe Ersquo presente frequentemente in giovani e sopratutto nei maschi La prognosi dellrsquo osteosarcoma degli arti trattata con solo amputazione puograve essere migliorata drammaticamente includendo la chemioterapia La chemioterapia neoadiuvante egrave comunemente usata per eradicare le micrometastasi e per preparare gli arti alla chirurgia di salvataggioOggi giorno una chirurgia conservativa egrave possibile nella maggior parte dei pazienti incluso i bambini ed egrave anche libera da recidive nei casi di sopravvivenza nel 50-80 Alte dosi di metotressato doxorubicina cis-platino ed ifosfamide sono considerate i

farmaci piugrave attivi contro lrsquoosteosarcoma Bull Cancer 2006 Nov 193(11)1115-20

Definizione del linfoma di Hodgkin Un cancro del sistema immunitario nel quale si evidenzia la presenza di un tipo particolare di cellule dette Reed-Sternberg cell I due tipi principali di linfoma di Hodgkin sono il classico e il nodulare che rappresenta il principale I sintomi includono dolore e ingrossamento dei linfonodi della milza o altri tessuti immunitari Altri sintomi includono febbre perdita di peso fatica e sudorazione notturna

Definizione di linfoma non-Hodgkin Rappresenta una versione di cancro al sistema immunitario (linfociti) Il linfoma non-Hodgkin egrave presente a qualsiasi etagrave e spesso egrave caratterizzato da ingrossamento dei linfonodi febbre e perdita di peso Ci sono diversi tipi di linfoma non-Hodgkin i quali possono essere suddivisi in aggressive (a crescita veloce) e indolenti ( a crescita lenta e possono essere classificati in linfomi delle cellule B o delle cellule T Tra i linfomi delle cellule B ricordiamo il linfoma di Burkitt linfomi diffusi delle cellule B linfomi follicolari linfomi immunoblastici a cellule grandi linfomi di precursori delle cellule B e linfomi di cellule mantello Linfomi non-Hodgkin delle cellule T includono micosi funginee linfomi anaplastici a cellule grandi e linfomi di precursori delle cellule T Linfomi correlati a disordini linfoproliferativi presenti a seguito di trapianti di midollo osseo o di cellule staminali generalmente sono linfomi non-hodgkin di cellule B

Reed-Sternberg cell

ANTIMETABOLITI

1) Analoghi dellrsquoacido folico

2) Analoghi delle purine

3) Analoghi delle pirimidine

Analoghi dellrsquoacido folico

Analoghi dellrsquoacido folico

METOTREXATOIl metotrexato egrave un analogo dellrsquoacido folico e inibisce la diidrofolico reduttasi prevenendo la formazione dellrsquoacido

tetraidrofolico Questo acido egrave essenziale per la formazione delle purine e pirimidine componenti del DNA ed RNA Il

tetraidofolato egrave coinvolto anche nella sintesi di aminoacidi quali serina e metionina

La sua tossicitagrave egrave a carico di cellule ad alta velocitagrave di duplicazione quali quelle del midollo della pelle e dei capelli

Leuk Lymphoma 2011 Oct52(10)1882-90 Epub 2011 Jun 12High-dose methotrexate based chemotherapy with deferred radiation for treatment of newly diagnosed primary central nervous system lymphomaGerard LM Imrie KR Mangel J Buckstein R Doherty M Mackenzie R Cheung MCOdette Cancer Centre Sunnybrook Health Sciences Centre Toronto Ontario CanadaAbstractThe addition of high-dose methotrexate (HD-MTX) to whole-brain radiation therapy (WBRT) has improved the survival of patients with primary central nervous system lymphoma (PCNSL) However combined therapy is associated with increased neurotoxicity In an effort to limit this toxicity we treated a series of non-immunocompromised patients with HDMVP a HD-MTX based regimen with deferral of WBRT until progression Twenty-three patients were treated with the HDMVP regimen consisting of MTX vincristine and procarbazine The mean age at diagnosis was 609 years (range 45-79 years) The overall response rate was 65 (14 complete responses and one partial response) For patients achieving an initial response with HDMVP the median response duration was 404 months (95 confidence interval [CI] 195-613) The median progression-free survival was 46 months (95 CI 00-204) and median overall survival was 414 months (95 CI 00-955) Fourteen patients received WBRT for relapsed or progressive disease The conclusion of this trial is that HDVMP results in good initial response rates but only moderate disease control Ultimately the majority of the patients in this series required WBRT for salvage treatment potentially enabling a delay in treatment-associated neurotoxicityPMID 21663504 [PubMed - in process]

CLASSI DI FARMACI ANTITUMORALI

1) Agenti alchilanti

2) Antimetaboliti

3) Antimitotici

4) Alcaloidi di origine vegetale

5) Antibiotici antitumorali

6) Inibitori Topoisomerasi

7) Anticorpi monoclonali

8) Inibitori dei fattori di crescita

AGENTI ALCHILANTI

A) Alchil sulfonati (busulfano)

B) Nitrosouree (Carmustina Lomustina)

C) Mostarde azotate ( Ciclofosfamide Mecloretamina uramustina

Melphalan clorambucile ifosfamide)

D) Composti del Platino (Cis-platino Carboplatino Oxaliplatino)

E) Idrazine (Procarbazina)

F) Tiazine (Dacarbazina)

G) Aziridine (Tiotepa)

Nitrosuree

1) Carmustina2) Streptozocina

Imidazotetrazine

Temozolimide

Lomustina

Mostarde azotate

Cyclophosphamide

Mecloretamina

Melphalan Clorambucile

Composti antitumorali del platino

1) Cisplatino

2) Carboplatino

3) Oxaliplatino

4) Tetranitrato triplatino

Idrazine

Procarbazina

Tiazine

Dacarbazina Tiotepa

Aziridine

La dacarbazina egrave un agente alchilante usata nel melanoma maligno nel linfoma di Hodgkin nei sarcomi e nei carcinomi del pancreas

Meccanismo di azione degli agenti alchilanti

Gli agenti alchilanti si legano con molte molecole intracellulari tra cui gli acidi

nucleici impedendone la lettura e quindi la trascrizione La citotossicitagrave egrave

primariamente dovuta al legame crociato tra filamenti di DNA ed RNA cosigrave

come allrsquoinibizione della sintesi proteica

Il busulfano egrave il solo agente usato nei regimi di mielosoppressione nei trapianti di cellule staminali ematopoietiche per la quale il monitoraggio terapeutico del farmaco egrave largamente usato Lrsquouso di busulfano per via orale porta ad una grande variabilitagrave intrapaziente e interpaziente in termini farmacocinetici specialmente nei bambini e lrsquoaggiustamento delle dosi egrave necessario per una ridotta tossicitagrave e migliore riuscita terapeutica Lrsquouso di busulfano per via endovenosa sta prendendo piede in quando porta a dei profili farmacocinetici piugrave controllabili La meningite neoplasica rappresenta il 5 dei tumori Ersquo una malattia che colpisce lrsquointero neuroasse e i farmaci devono passare nel fluido cefalorachidiano Oggigiorno la terapia con farmaci direttamente immessi nel liquido cefalorachidiano egrave ristretta a tre farmaci Il metotressato la citarabina ed il tiotepa Il cis-platino egrave un antitumorale usato per trattare vari tipi di cancro tipo sarcoma carcinosarcomi (piccolo cellule del polmone cancro ovarico) linfomi Ersquo il primo di una classe che va in crescendo di nuovi composti quali il carboplatino lrsquooxaliplatino Questi composti formano dei complessi allrsquointerno della cellula tumorale i quali legano il DNA attraverso legami intracatena e tra catene di DNA A questo segue lrsquoapoptosi cellulare

Although the entity we refer today as chronic myeloid leukemia (CML) was probably first described in the early nineteenth century there was little progress in understanding its biology until the discovery of the Philadelphia (Ph) chromosome in 19601 Subsequent important landmarks were the recognition that the Ph chromosome results from a t(922) translocation the demonstration that the leukemia probably originates from a single hematopoietic ldquostem cellrdquo the identification of the breakpoint cluster region (BCR) on chromosome no 22 and subsequently of the BCR-ABL fusion gene and more recently thedevelopment of a murine model simulating the human disease23 Treatment in the 19th century was unsatisfactory although arsenicals induced some degree of symptomatic control In the early 20th century radiotherapy was helpful but it was replaced in the 1950s by busulfan which remained popular for some years despite the emerging suspicion that this alkylating agent might in fact predispose to progression to advanced-phase disease In due course hydroxycarbamide replaced busulfan but interferon-alfa the first agent to induce any degree of Ph-chromosome negativity in the bone marrow was introduced in the early 1980s and became the treatment of choice for patients not eligible for allogeneic stem cell transplantation Between 1980 and 2000 allografting despite the risks of morbidity and mortality was the recommended initial treatment for younger patients with HLA-matched donors Therapy has now been ldquorevolutionizedrdquo by the introduction of imatinib (imatinib mesylate IM) the original Abl tyrosine kinase inhibitor (TKI) which was used first in the clinic in 1998

(Blood 20071102828-2837)

Lrsquoosteosarcoma egrave un cancro a carico dellrsquoosso e generalmente colpisce le ossa grandi delle braccia e delle gambe Ersquo presente frequentemente in giovani e sopratutto nei maschi La prognosi dellrsquo osteosarcoma degli arti trattata con solo amputazione puograve essere migliorata drammaticamente includendo la chemioterapia La chemioterapia neoadiuvante egrave comunemente usata per eradicare le micrometastasi e per preparare gli arti alla chirurgia di salvataggioOggi giorno una chirurgia conservativa egrave possibile nella maggior parte dei pazienti incluso i bambini ed egrave anche libera da recidive nei casi di sopravvivenza nel 50-80 Alte dosi di metotressato doxorubicina cis-platino ed ifosfamide sono considerate i

farmaci piugrave attivi contro lrsquoosteosarcoma Bull Cancer 2006 Nov 193(11)1115-20

Definizione del linfoma di Hodgkin Un cancro del sistema immunitario nel quale si evidenzia la presenza di un tipo particolare di cellule dette Reed-Sternberg cell I due tipi principali di linfoma di Hodgkin sono il classico e il nodulare che rappresenta il principale I sintomi includono dolore e ingrossamento dei linfonodi della milza o altri tessuti immunitari Altri sintomi includono febbre perdita di peso fatica e sudorazione notturna

Definizione di linfoma non-Hodgkin Rappresenta una versione di cancro al sistema immunitario (linfociti) Il linfoma non-Hodgkin egrave presente a qualsiasi etagrave e spesso egrave caratterizzato da ingrossamento dei linfonodi febbre e perdita di peso Ci sono diversi tipi di linfoma non-Hodgkin i quali possono essere suddivisi in aggressive (a crescita veloce) e indolenti ( a crescita lenta e possono essere classificati in linfomi delle cellule B o delle cellule T Tra i linfomi delle cellule B ricordiamo il linfoma di Burkitt linfomi diffusi delle cellule B linfomi follicolari linfomi immunoblastici a cellule grandi linfomi di precursori delle cellule B e linfomi di cellule mantello Linfomi non-Hodgkin delle cellule T includono micosi funginee linfomi anaplastici a cellule grandi e linfomi di precursori delle cellule T Linfomi correlati a disordini linfoproliferativi presenti a seguito di trapianti di midollo osseo o di cellule staminali generalmente sono linfomi non-hodgkin di cellule B

Reed-Sternberg cell

ANTIMETABOLITI

1) Analoghi dellrsquoacido folico

2) Analoghi delle purine

3) Analoghi delle pirimidine

Analoghi dellrsquoacido folico

Analoghi dellrsquoacido folico

METOTREXATOIl metotrexato egrave un analogo dellrsquoacido folico e inibisce la diidrofolico reduttasi prevenendo la formazione dellrsquoacido

tetraidrofolico Questo acido egrave essenziale per la formazione delle purine e pirimidine componenti del DNA ed RNA Il

tetraidofolato egrave coinvolto anche nella sintesi di aminoacidi quali serina e metionina

La sua tossicitagrave egrave a carico di cellule ad alta velocitagrave di duplicazione quali quelle del midollo della pelle e dei capelli

Leuk Lymphoma 2011 Oct52(10)1882-90 Epub 2011 Jun 12High-dose methotrexate based chemotherapy with deferred radiation for treatment of newly diagnosed primary central nervous system lymphomaGerard LM Imrie KR Mangel J Buckstein R Doherty M Mackenzie R Cheung MCOdette Cancer Centre Sunnybrook Health Sciences Centre Toronto Ontario CanadaAbstractThe addition of high-dose methotrexate (HD-MTX) to whole-brain radiation therapy (WBRT) has improved the survival of patients with primary central nervous system lymphoma (PCNSL) However combined therapy is associated with increased neurotoxicity In an effort to limit this toxicity we treated a series of non-immunocompromised patients with HDMVP a HD-MTX based regimen with deferral of WBRT until progression Twenty-three patients were treated with the HDMVP regimen consisting of MTX vincristine and procarbazine The mean age at diagnosis was 609 years (range 45-79 years) The overall response rate was 65 (14 complete responses and one partial response) For patients achieving an initial response with HDMVP the median response duration was 404 months (95 confidence interval [CI] 195-613) The median progression-free survival was 46 months (95 CI 00-204) and median overall survival was 414 months (95 CI 00-955) Fourteen patients received WBRT for relapsed or progressive disease The conclusion of this trial is that HDVMP results in good initial response rates but only moderate disease control Ultimately the majority of the patients in this series required WBRT for salvage treatment potentially enabling a delay in treatment-associated neurotoxicityPMID 21663504 [PubMed - in process]

AGENTI ALCHILANTI

A) Alchil sulfonati (busulfano)

B) Nitrosouree (Carmustina Lomustina)

C) Mostarde azotate ( Ciclofosfamide Mecloretamina uramustina

Melphalan clorambucile ifosfamide)

D) Composti del Platino (Cis-platino Carboplatino Oxaliplatino)

E) Idrazine (Procarbazina)

F) Tiazine (Dacarbazina)

G) Aziridine (Tiotepa)

Nitrosuree

1) Carmustina2) Streptozocina

Imidazotetrazine

Temozolimide

Lomustina

Mostarde azotate

Cyclophosphamide

Mecloretamina

Melphalan Clorambucile

Composti antitumorali del platino

1) Cisplatino

2) Carboplatino

3) Oxaliplatino

4) Tetranitrato triplatino

Idrazine

Procarbazina

Tiazine

Dacarbazina Tiotepa

Aziridine

La dacarbazina egrave un agente alchilante usata nel melanoma maligno nel linfoma di Hodgkin nei sarcomi e nei carcinomi del pancreas

Meccanismo di azione degli agenti alchilanti

Gli agenti alchilanti si legano con molte molecole intracellulari tra cui gli acidi

nucleici impedendone la lettura e quindi la trascrizione La citotossicitagrave egrave

primariamente dovuta al legame crociato tra filamenti di DNA ed RNA cosigrave

come allrsquoinibizione della sintesi proteica

Il busulfano egrave il solo agente usato nei regimi di mielosoppressione nei trapianti di cellule staminali ematopoietiche per la quale il monitoraggio terapeutico del farmaco egrave largamente usato Lrsquouso di busulfano per via orale porta ad una grande variabilitagrave intrapaziente e interpaziente in termini farmacocinetici specialmente nei bambini e lrsquoaggiustamento delle dosi egrave necessario per una ridotta tossicitagrave e migliore riuscita terapeutica Lrsquouso di busulfano per via endovenosa sta prendendo piede in quando porta a dei profili farmacocinetici piugrave controllabili La meningite neoplasica rappresenta il 5 dei tumori Ersquo una malattia che colpisce lrsquointero neuroasse e i farmaci devono passare nel fluido cefalorachidiano Oggigiorno la terapia con farmaci direttamente immessi nel liquido cefalorachidiano egrave ristretta a tre farmaci Il metotressato la citarabina ed il tiotepa Il cis-platino egrave un antitumorale usato per trattare vari tipi di cancro tipo sarcoma carcinosarcomi (piccolo cellule del polmone cancro ovarico) linfomi Ersquo il primo di una classe che va in crescendo di nuovi composti quali il carboplatino lrsquooxaliplatino Questi composti formano dei complessi allrsquointerno della cellula tumorale i quali legano il DNA attraverso legami intracatena e tra catene di DNA A questo segue lrsquoapoptosi cellulare

Although the entity we refer today as chronic myeloid leukemia (CML) was probably first described in the early nineteenth century there was little progress in understanding its biology until the discovery of the Philadelphia (Ph) chromosome in 19601 Subsequent important landmarks were the recognition that the Ph chromosome results from a t(922) translocation the demonstration that the leukemia probably originates from a single hematopoietic ldquostem cellrdquo the identification of the breakpoint cluster region (BCR) on chromosome no 22 and subsequently of the BCR-ABL fusion gene and more recently thedevelopment of a murine model simulating the human disease23 Treatment in the 19th century was unsatisfactory although arsenicals induced some degree of symptomatic control In the early 20th century radiotherapy was helpful but it was replaced in the 1950s by busulfan which remained popular for some years despite the emerging suspicion that this alkylating agent might in fact predispose to progression to advanced-phase disease In due course hydroxycarbamide replaced busulfan but interferon-alfa the first agent to induce any degree of Ph-chromosome negativity in the bone marrow was introduced in the early 1980s and became the treatment of choice for patients not eligible for allogeneic stem cell transplantation Between 1980 and 2000 allografting despite the risks of morbidity and mortality was the recommended initial treatment for younger patients with HLA-matched donors Therapy has now been ldquorevolutionizedrdquo by the introduction of imatinib (imatinib mesylate IM) the original Abl tyrosine kinase inhibitor (TKI) which was used first in the clinic in 1998

(Blood 20071102828-2837)

Lrsquoosteosarcoma egrave un cancro a carico dellrsquoosso e generalmente colpisce le ossa grandi delle braccia e delle gambe Ersquo presente frequentemente in giovani e sopratutto nei maschi La prognosi dellrsquo osteosarcoma degli arti trattata con solo amputazione puograve essere migliorata drammaticamente includendo la chemioterapia La chemioterapia neoadiuvante egrave comunemente usata per eradicare le micrometastasi e per preparare gli arti alla chirurgia di salvataggioOggi giorno una chirurgia conservativa egrave possibile nella maggior parte dei pazienti incluso i bambini ed egrave anche libera da recidive nei casi di sopravvivenza nel 50-80 Alte dosi di metotressato doxorubicina cis-platino ed ifosfamide sono considerate i

farmaci piugrave attivi contro lrsquoosteosarcoma Bull Cancer 2006 Nov 193(11)1115-20

Definizione del linfoma di Hodgkin Un cancro del sistema immunitario nel quale si evidenzia la presenza di un tipo particolare di cellule dette Reed-Sternberg cell I due tipi principali di linfoma di Hodgkin sono il classico e il nodulare che rappresenta il principale I sintomi includono dolore e ingrossamento dei linfonodi della milza o altri tessuti immunitari Altri sintomi includono febbre perdita di peso fatica e sudorazione notturna

Definizione di linfoma non-Hodgkin Rappresenta una versione di cancro al sistema immunitario (linfociti) Il linfoma non-Hodgkin egrave presente a qualsiasi etagrave e spesso egrave caratterizzato da ingrossamento dei linfonodi febbre e perdita di peso Ci sono diversi tipi di linfoma non-Hodgkin i quali possono essere suddivisi in aggressive (a crescita veloce) e indolenti ( a crescita lenta e possono essere classificati in linfomi delle cellule B o delle cellule T Tra i linfomi delle cellule B ricordiamo il linfoma di Burkitt linfomi diffusi delle cellule B linfomi follicolari linfomi immunoblastici a cellule grandi linfomi di precursori delle cellule B e linfomi di cellule mantello Linfomi non-Hodgkin delle cellule T includono micosi funginee linfomi anaplastici a cellule grandi e linfomi di precursori delle cellule T Linfomi correlati a disordini linfoproliferativi presenti a seguito di trapianti di midollo osseo o di cellule staminali generalmente sono linfomi non-hodgkin di cellule B

Reed-Sternberg cell

ANTIMETABOLITI

1) Analoghi dellrsquoacido folico

2) Analoghi delle purine

3) Analoghi delle pirimidine

Analoghi dellrsquoacido folico

Analoghi dellrsquoacido folico

METOTREXATOIl metotrexato egrave un analogo dellrsquoacido folico e inibisce la diidrofolico reduttasi prevenendo la formazione dellrsquoacido

tetraidrofolico Questo acido egrave essenziale per la formazione delle purine e pirimidine componenti del DNA ed RNA Il

tetraidofolato egrave coinvolto anche nella sintesi di aminoacidi quali serina e metionina

La sua tossicitagrave egrave a carico di cellule ad alta velocitagrave di duplicazione quali quelle del midollo della pelle e dei capelli

Leuk Lymphoma 2011 Oct52(10)1882-90 Epub 2011 Jun 12High-dose methotrexate based chemotherapy with deferred radiation for treatment of newly diagnosed primary central nervous system lymphomaGerard LM Imrie KR Mangel J Buckstein R Doherty M Mackenzie R Cheung MCOdette Cancer Centre Sunnybrook Health Sciences Centre Toronto Ontario CanadaAbstractThe addition of high-dose methotrexate (HD-MTX) to whole-brain radiation therapy (WBRT) has improved the survival of patients with primary central nervous system lymphoma (PCNSL) However combined therapy is associated with increased neurotoxicity In an effort to limit this toxicity we treated a series of non-immunocompromised patients with HDMVP a HD-MTX based regimen with deferral of WBRT until progression Twenty-three patients were treated with the HDMVP regimen consisting of MTX vincristine and procarbazine The mean age at diagnosis was 609 years (range 45-79 years) The overall response rate was 65 (14 complete responses and one partial response) For patients achieving an initial response with HDMVP the median response duration was 404 months (95 confidence interval [CI] 195-613) The median progression-free survival was 46 months (95 CI 00-204) and median overall survival was 414 months (95 CI 00-955) Fourteen patients received WBRT for relapsed or progressive disease The conclusion of this trial is that HDVMP results in good initial response rates but only moderate disease control Ultimately the majority of the patients in this series required WBRT for salvage treatment potentially enabling a delay in treatment-associated neurotoxicityPMID 21663504 [PubMed - in process]

Nitrosuree

1) Carmustina2) Streptozocina

Imidazotetrazine

Temozolimide

Lomustina

Mostarde azotate

Cyclophosphamide

Mecloretamina

Melphalan Clorambucile

Composti antitumorali del platino

1) Cisplatino

2) Carboplatino

3) Oxaliplatino

4) Tetranitrato triplatino

Idrazine

Procarbazina

Tiazine

Dacarbazina Tiotepa

Aziridine

La dacarbazina egrave un agente alchilante usata nel melanoma maligno nel linfoma di Hodgkin nei sarcomi e nei carcinomi del pancreas

Meccanismo di azione degli agenti alchilanti

Gli agenti alchilanti si legano con molte molecole intracellulari tra cui gli acidi

nucleici impedendone la lettura e quindi la trascrizione La citotossicitagrave egrave

primariamente dovuta al legame crociato tra filamenti di DNA ed RNA cosigrave

come allrsquoinibizione della sintesi proteica

Il busulfano egrave il solo agente usato nei regimi di mielosoppressione nei trapianti di cellule staminali ematopoietiche per la quale il monitoraggio terapeutico del farmaco egrave largamente usato Lrsquouso di busulfano per via orale porta ad una grande variabilitagrave intrapaziente e interpaziente in termini farmacocinetici specialmente nei bambini e lrsquoaggiustamento delle dosi egrave necessario per una ridotta tossicitagrave e migliore riuscita terapeutica Lrsquouso di busulfano per via endovenosa sta prendendo piede in quando porta a dei profili farmacocinetici piugrave controllabili La meningite neoplasica rappresenta il 5 dei tumori Ersquo una malattia che colpisce lrsquointero neuroasse e i farmaci devono passare nel fluido cefalorachidiano Oggigiorno la terapia con farmaci direttamente immessi nel liquido cefalorachidiano egrave ristretta a tre farmaci Il metotressato la citarabina ed il tiotepa Il cis-platino egrave un antitumorale usato per trattare vari tipi di cancro tipo sarcoma carcinosarcomi (piccolo cellule del polmone cancro ovarico) linfomi Ersquo il primo di una classe che va in crescendo di nuovi composti quali il carboplatino lrsquooxaliplatino Questi composti formano dei complessi allrsquointerno della cellula tumorale i quali legano il DNA attraverso legami intracatena e tra catene di DNA A questo segue lrsquoapoptosi cellulare

Although the entity we refer today as chronic myeloid leukemia (CML) was probably first described in the early nineteenth century there was little progress in understanding its biology until the discovery of the Philadelphia (Ph) chromosome in 19601 Subsequent important landmarks were the recognition that the Ph chromosome results from a t(922) translocation the demonstration that the leukemia probably originates from a single hematopoietic ldquostem cellrdquo the identification of the breakpoint cluster region (BCR) on chromosome no 22 and subsequently of the BCR-ABL fusion gene and more recently thedevelopment of a murine model simulating the human disease23 Treatment in the 19th century was unsatisfactory although arsenicals induced some degree of symptomatic control In the early 20th century radiotherapy was helpful but it was replaced in the 1950s by busulfan which remained popular for some years despite the emerging suspicion that this alkylating agent might in fact predispose to progression to advanced-phase disease In due course hydroxycarbamide replaced busulfan but interferon-alfa the first agent to induce any degree of Ph-chromosome negativity in the bone marrow was introduced in the early 1980s and became the treatment of choice for patients not eligible for allogeneic stem cell transplantation Between 1980 and 2000 allografting despite the risks of morbidity and mortality was the recommended initial treatment for younger patients with HLA-matched donors Therapy has now been ldquorevolutionizedrdquo by the introduction of imatinib (imatinib mesylate IM) the original Abl tyrosine kinase inhibitor (TKI) which was used first in the clinic in 1998

(Blood 20071102828-2837)

Lrsquoosteosarcoma egrave un cancro a carico dellrsquoosso e generalmente colpisce le ossa grandi delle braccia e delle gambe Ersquo presente frequentemente in giovani e sopratutto nei maschi La prognosi dellrsquo osteosarcoma degli arti trattata con solo amputazione puograve essere migliorata drammaticamente includendo la chemioterapia La chemioterapia neoadiuvante egrave comunemente usata per eradicare le micrometastasi e per preparare gli arti alla chirurgia di salvataggioOggi giorno una chirurgia conservativa egrave possibile nella maggior parte dei pazienti incluso i bambini ed egrave anche libera da recidive nei casi di sopravvivenza nel 50-80 Alte dosi di metotressato doxorubicina cis-platino ed ifosfamide sono considerate i

farmaci piugrave attivi contro lrsquoosteosarcoma Bull Cancer 2006 Nov 193(11)1115-20

Definizione del linfoma di Hodgkin Un cancro del sistema immunitario nel quale si evidenzia la presenza di un tipo particolare di cellule dette Reed-Sternberg cell I due tipi principali di linfoma di Hodgkin sono il classico e il nodulare che rappresenta il principale I sintomi includono dolore e ingrossamento dei linfonodi della milza o altri tessuti immunitari Altri sintomi includono febbre perdita di peso fatica e sudorazione notturna

Definizione di linfoma non-Hodgkin Rappresenta una versione di cancro al sistema immunitario (linfociti) Il linfoma non-Hodgkin egrave presente a qualsiasi etagrave e spesso egrave caratterizzato da ingrossamento dei linfonodi febbre e perdita di peso Ci sono diversi tipi di linfoma non-Hodgkin i quali possono essere suddivisi in aggressive (a crescita veloce) e indolenti ( a crescita lenta e possono essere classificati in linfomi delle cellule B o delle cellule T Tra i linfomi delle cellule B ricordiamo il linfoma di Burkitt linfomi diffusi delle cellule B linfomi follicolari linfomi immunoblastici a cellule grandi linfomi di precursori delle cellule B e linfomi di cellule mantello Linfomi non-Hodgkin delle cellule T includono micosi funginee linfomi anaplastici a cellule grandi e linfomi di precursori delle cellule T Linfomi correlati a disordini linfoproliferativi presenti a seguito di trapianti di midollo osseo o di cellule staminali generalmente sono linfomi non-hodgkin di cellule B

Reed-Sternberg cell

ANTIMETABOLITI

1) Analoghi dellrsquoacido folico

2) Analoghi delle purine

3) Analoghi delle pirimidine

Analoghi dellrsquoacido folico

Analoghi dellrsquoacido folico

METOTREXATOIl metotrexato egrave un analogo dellrsquoacido folico e inibisce la diidrofolico reduttasi prevenendo la formazione dellrsquoacido

tetraidrofolico Questo acido egrave essenziale per la formazione delle purine e pirimidine componenti del DNA ed RNA Il

tetraidofolato egrave coinvolto anche nella sintesi di aminoacidi quali serina e metionina

La sua tossicitagrave egrave a carico di cellule ad alta velocitagrave di duplicazione quali quelle del midollo della pelle e dei capelli

Leuk Lymphoma 2011 Oct52(10)1882-90 Epub 2011 Jun 12High-dose methotrexate based chemotherapy with deferred radiation for treatment of newly diagnosed primary central nervous system lymphomaGerard LM Imrie KR Mangel J Buckstein R Doherty M Mackenzie R Cheung MCOdette Cancer Centre Sunnybrook Health Sciences Centre Toronto Ontario CanadaAbstractThe addition of high-dose methotrexate (HD-MTX) to whole-brain radiation therapy (WBRT) has improved the survival of patients with primary central nervous system lymphoma (PCNSL) However combined therapy is associated with increased neurotoxicity In an effort to limit this toxicity we treated a series of non-immunocompromised patients with HDMVP a HD-MTX based regimen with deferral of WBRT until progression Twenty-three patients were treated with the HDMVP regimen consisting of MTX vincristine and procarbazine The mean age at diagnosis was 609 years (range 45-79 years) The overall response rate was 65 (14 complete responses and one partial response) For patients achieving an initial response with HDMVP the median response duration was 404 months (95 confidence interval [CI] 195-613) The median progression-free survival was 46 months (95 CI 00-204) and median overall survival was 414 months (95 CI 00-955) Fourteen patients received WBRT for relapsed or progressive disease The conclusion of this trial is that HDVMP results in good initial response rates but only moderate disease control Ultimately the majority of the patients in this series required WBRT for salvage treatment potentially enabling a delay in treatment-associated neurotoxicityPMID 21663504 [PubMed - in process]

Mostarde azotate

Cyclophosphamide

Mecloretamina

Melphalan Clorambucile

Composti antitumorali del platino

1) Cisplatino

2) Carboplatino

3) Oxaliplatino

4) Tetranitrato triplatino

Idrazine

Procarbazina

Tiazine

Dacarbazina Tiotepa

Aziridine

La dacarbazina egrave un agente alchilante usata nel melanoma maligno nel linfoma di Hodgkin nei sarcomi e nei carcinomi del pancreas

Meccanismo di azione degli agenti alchilanti

Gli agenti alchilanti si legano con molte molecole intracellulari tra cui gli acidi

nucleici impedendone la lettura e quindi la trascrizione La citotossicitagrave egrave

primariamente dovuta al legame crociato tra filamenti di DNA ed RNA cosigrave

come allrsquoinibizione della sintesi proteica

Il busulfano egrave il solo agente usato nei regimi di mielosoppressione nei trapianti di cellule staminali ematopoietiche per la quale il monitoraggio terapeutico del farmaco egrave largamente usato Lrsquouso di busulfano per via orale porta ad una grande variabilitagrave intrapaziente e interpaziente in termini farmacocinetici specialmente nei bambini e lrsquoaggiustamento delle dosi egrave necessario per una ridotta tossicitagrave e migliore riuscita terapeutica Lrsquouso di busulfano per via endovenosa sta prendendo piede in quando porta a dei profili farmacocinetici piugrave controllabili La meningite neoplasica rappresenta il 5 dei tumori Ersquo una malattia che colpisce lrsquointero neuroasse e i farmaci devono passare nel fluido cefalorachidiano Oggigiorno la terapia con farmaci direttamente immessi nel liquido cefalorachidiano egrave ristretta a tre farmaci Il metotressato la citarabina ed il tiotepa Il cis-platino egrave un antitumorale usato per trattare vari tipi di cancro tipo sarcoma carcinosarcomi (piccolo cellule del polmone cancro ovarico) linfomi Ersquo il primo di una classe che va in crescendo di nuovi composti quali il carboplatino lrsquooxaliplatino Questi composti formano dei complessi allrsquointerno della cellula tumorale i quali legano il DNA attraverso legami intracatena e tra catene di DNA A questo segue lrsquoapoptosi cellulare

Although the entity we refer today as chronic myeloid leukemia (CML) was probably first described in the early nineteenth century there was little progress in understanding its biology until the discovery of the Philadelphia (Ph) chromosome in 19601 Subsequent important landmarks were the recognition that the Ph chromosome results from a t(922) translocation the demonstration that the leukemia probably originates from a single hematopoietic ldquostem cellrdquo the identification of the breakpoint cluster region (BCR) on chromosome no 22 and subsequently of the BCR-ABL fusion gene and more recently thedevelopment of a murine model simulating the human disease23 Treatment in the 19th century was unsatisfactory although arsenicals induced some degree of symptomatic control In the early 20th century radiotherapy was helpful but it was replaced in the 1950s by busulfan which remained popular for some years despite the emerging suspicion that this alkylating agent might in fact predispose to progression to advanced-phase disease In due course hydroxycarbamide replaced busulfan but interferon-alfa the first agent to induce any degree of Ph-chromosome negativity in the bone marrow was introduced in the early 1980s and became the treatment of choice for patients not eligible for allogeneic stem cell transplantation Between 1980 and 2000 allografting despite the risks of morbidity and mortality was the recommended initial treatment for younger patients with HLA-matched donors Therapy has now been ldquorevolutionizedrdquo by the introduction of imatinib (imatinib mesylate IM) the original Abl tyrosine kinase inhibitor (TKI) which was used first in the clinic in 1998

(Blood 20071102828-2837)

Lrsquoosteosarcoma egrave un cancro a carico dellrsquoosso e generalmente colpisce le ossa grandi delle braccia e delle gambe Ersquo presente frequentemente in giovani e sopratutto nei maschi La prognosi dellrsquo osteosarcoma degli arti trattata con solo amputazione puograve essere migliorata drammaticamente includendo la chemioterapia La chemioterapia neoadiuvante egrave comunemente usata per eradicare le micrometastasi e per preparare gli arti alla chirurgia di salvataggioOggi giorno una chirurgia conservativa egrave possibile nella maggior parte dei pazienti incluso i bambini ed egrave anche libera da recidive nei casi di sopravvivenza nel 50-80 Alte dosi di metotressato doxorubicina cis-platino ed ifosfamide sono considerate i

farmaci piugrave attivi contro lrsquoosteosarcoma Bull Cancer 2006 Nov 193(11)1115-20

Definizione del linfoma di Hodgkin Un cancro del sistema immunitario nel quale si evidenzia la presenza di un tipo particolare di cellule dette Reed-Sternberg cell I due tipi principali di linfoma di Hodgkin sono il classico e il nodulare che rappresenta il principale I sintomi includono dolore e ingrossamento dei linfonodi della milza o altri tessuti immunitari Altri sintomi includono febbre perdita di peso fatica e sudorazione notturna

Definizione di linfoma non-Hodgkin Rappresenta una versione di cancro al sistema immunitario (linfociti) Il linfoma non-Hodgkin egrave presente a qualsiasi etagrave e spesso egrave caratterizzato da ingrossamento dei linfonodi febbre e perdita di peso Ci sono diversi tipi di linfoma non-Hodgkin i quali possono essere suddivisi in aggressive (a crescita veloce) e indolenti ( a crescita lenta e possono essere classificati in linfomi delle cellule B o delle cellule T Tra i linfomi delle cellule B ricordiamo il linfoma di Burkitt linfomi diffusi delle cellule B linfomi follicolari linfomi immunoblastici a cellule grandi linfomi di precursori delle cellule B e linfomi di cellule mantello Linfomi non-Hodgkin delle cellule T includono micosi funginee linfomi anaplastici a cellule grandi e linfomi di precursori delle cellule T Linfomi correlati a disordini linfoproliferativi presenti a seguito di trapianti di midollo osseo o di cellule staminali generalmente sono linfomi non-hodgkin di cellule B

Reed-Sternberg cell

ANTIMETABOLITI

1) Analoghi dellrsquoacido folico

2) Analoghi delle purine

3) Analoghi delle pirimidine

Analoghi dellrsquoacido folico

Analoghi dellrsquoacido folico

METOTREXATOIl metotrexato egrave un analogo dellrsquoacido folico e inibisce la diidrofolico reduttasi prevenendo la formazione dellrsquoacido

tetraidrofolico Questo acido egrave essenziale per la formazione delle purine e pirimidine componenti del DNA ed RNA Il

tetraidofolato egrave coinvolto anche nella sintesi di aminoacidi quali serina e metionina

La sua tossicitagrave egrave a carico di cellule ad alta velocitagrave di duplicazione quali quelle del midollo della pelle e dei capelli

Leuk Lymphoma 2011 Oct52(10)1882-90 Epub 2011 Jun 12High-dose methotrexate based chemotherapy with deferred radiation for treatment of newly diagnosed primary central nervous system lymphomaGerard LM Imrie KR Mangel J Buckstein R Doherty M Mackenzie R Cheung MCOdette Cancer Centre Sunnybrook Health Sciences Centre Toronto Ontario CanadaAbstractThe addition of high-dose methotrexate (HD-MTX) to whole-brain radiation therapy (WBRT) has improved the survival of patients with primary central nervous system lymphoma (PCNSL) However combined therapy is associated with increased neurotoxicity In an effort to limit this toxicity we treated a series of non-immunocompromised patients with HDMVP a HD-MTX based regimen with deferral of WBRT until progression Twenty-three patients were treated with the HDMVP regimen consisting of MTX vincristine and procarbazine The mean age at diagnosis was 609 years (range 45-79 years) The overall response rate was 65 (14 complete responses and one partial response) For patients achieving an initial response with HDMVP the median response duration was 404 months (95 confidence interval [CI] 195-613) The median progression-free survival was 46 months (95 CI 00-204) and median overall survival was 414 months (95 CI 00-955) Fourteen patients received WBRT for relapsed or progressive disease The conclusion of this trial is that HDVMP results in good initial response rates but only moderate disease control Ultimately the majority of the patients in this series required WBRT for salvage treatment potentially enabling a delay in treatment-associated neurotoxicityPMID 21663504 [PubMed - in process]

Composti antitumorali del platino

1) Cisplatino

2) Carboplatino

3) Oxaliplatino

4) Tetranitrato triplatino

Idrazine

Procarbazina

Tiazine

Dacarbazina Tiotepa

Aziridine

La dacarbazina egrave un agente alchilante usata nel melanoma maligno nel linfoma di Hodgkin nei sarcomi e nei carcinomi del pancreas

Meccanismo di azione degli agenti alchilanti

Gli agenti alchilanti si legano con molte molecole intracellulari tra cui gli acidi

nucleici impedendone la lettura e quindi la trascrizione La citotossicitagrave egrave

primariamente dovuta al legame crociato tra filamenti di DNA ed RNA cosigrave

come allrsquoinibizione della sintesi proteica

Il busulfano egrave il solo agente usato nei regimi di mielosoppressione nei trapianti di cellule staminali ematopoietiche per la quale il monitoraggio terapeutico del farmaco egrave largamente usato Lrsquouso di busulfano per via orale porta ad una grande variabilitagrave intrapaziente e interpaziente in termini farmacocinetici specialmente nei bambini e lrsquoaggiustamento delle dosi egrave necessario per una ridotta tossicitagrave e migliore riuscita terapeutica Lrsquouso di busulfano per via endovenosa sta prendendo piede in quando porta a dei profili farmacocinetici piugrave controllabili La meningite neoplasica rappresenta il 5 dei tumori Ersquo una malattia che colpisce lrsquointero neuroasse e i farmaci devono passare nel fluido cefalorachidiano Oggigiorno la terapia con farmaci direttamente immessi nel liquido cefalorachidiano egrave ristretta a tre farmaci Il metotressato la citarabina ed il tiotepa Il cis-platino egrave un antitumorale usato per trattare vari tipi di cancro tipo sarcoma carcinosarcomi (piccolo cellule del polmone cancro ovarico) linfomi Ersquo il primo di una classe che va in crescendo di nuovi composti quali il carboplatino lrsquooxaliplatino Questi composti formano dei complessi allrsquointerno della cellula tumorale i quali legano il DNA attraverso legami intracatena e tra catene di DNA A questo segue lrsquoapoptosi cellulare

Although the entity we refer today as chronic myeloid leukemia (CML) was probably first described in the early nineteenth century there was little progress in understanding its biology until the discovery of the Philadelphia (Ph) chromosome in 19601 Subsequent important landmarks were the recognition that the Ph chromosome results from a t(922) translocation the demonstration that the leukemia probably originates from a single hematopoietic ldquostem cellrdquo the identification of the breakpoint cluster region (BCR) on chromosome no 22 and subsequently of the BCR-ABL fusion gene and more recently thedevelopment of a murine model simulating the human disease23 Treatment in the 19th century was unsatisfactory although arsenicals induced some degree of symptomatic control In the early 20th century radiotherapy was helpful but it was replaced in the 1950s by busulfan which remained popular for some years despite the emerging suspicion that this alkylating agent might in fact predispose to progression to advanced-phase disease In due course hydroxycarbamide replaced busulfan but interferon-alfa the first agent to induce any degree of Ph-chromosome negativity in the bone marrow was introduced in the early 1980s and became the treatment of choice for patients not eligible for allogeneic stem cell transplantation Between 1980 and 2000 allografting despite the risks of morbidity and mortality was the recommended initial treatment for younger patients with HLA-matched donors Therapy has now been ldquorevolutionizedrdquo by the introduction of imatinib (imatinib mesylate IM) the original Abl tyrosine kinase inhibitor (TKI) which was used first in the clinic in 1998

(Blood 20071102828-2837)

Lrsquoosteosarcoma egrave un cancro a carico dellrsquoosso e generalmente colpisce le ossa grandi delle braccia e delle gambe Ersquo presente frequentemente in giovani e sopratutto nei maschi La prognosi dellrsquo osteosarcoma degli arti trattata con solo amputazione puograve essere migliorata drammaticamente includendo la chemioterapia La chemioterapia neoadiuvante egrave comunemente usata per eradicare le micrometastasi e per preparare gli arti alla chirurgia di salvataggioOggi giorno una chirurgia conservativa egrave possibile nella maggior parte dei pazienti incluso i bambini ed egrave anche libera da recidive nei casi di sopravvivenza nel 50-80 Alte dosi di metotressato doxorubicina cis-platino ed ifosfamide sono considerate i

farmaci piugrave attivi contro lrsquoosteosarcoma Bull Cancer 2006 Nov 193(11)1115-20

Definizione del linfoma di Hodgkin Un cancro del sistema immunitario nel quale si evidenzia la presenza di un tipo particolare di cellule dette Reed-Sternberg cell I due tipi principali di linfoma di Hodgkin sono il classico e il nodulare che rappresenta il principale I sintomi includono dolore e ingrossamento dei linfonodi della milza o altri tessuti immunitari Altri sintomi includono febbre perdita di peso fatica e sudorazione notturna

Definizione di linfoma non-Hodgkin Rappresenta una versione di cancro al sistema immunitario (linfociti) Il linfoma non-Hodgkin egrave presente a qualsiasi etagrave e spesso egrave caratterizzato da ingrossamento dei linfonodi febbre e perdita di peso Ci sono diversi tipi di linfoma non-Hodgkin i quali possono essere suddivisi in aggressive (a crescita veloce) e indolenti ( a crescita lenta e possono essere classificati in linfomi delle cellule B o delle cellule T Tra i linfomi delle cellule B ricordiamo il linfoma di Burkitt linfomi diffusi delle cellule B linfomi follicolari linfomi immunoblastici a cellule grandi linfomi di precursori delle cellule B e linfomi di cellule mantello Linfomi non-Hodgkin delle cellule T includono micosi funginee linfomi anaplastici a cellule grandi e linfomi di precursori delle cellule T Linfomi correlati a disordini linfoproliferativi presenti a seguito di trapianti di midollo osseo o di cellule staminali generalmente sono linfomi non-hodgkin di cellule B

Reed-Sternberg cell

ANTIMETABOLITI

1) Analoghi dellrsquoacido folico

2) Analoghi delle purine

3) Analoghi delle pirimidine

Analoghi dellrsquoacido folico

Analoghi dellrsquoacido folico

METOTREXATOIl metotrexato egrave un analogo dellrsquoacido folico e inibisce la diidrofolico reduttasi prevenendo la formazione dellrsquoacido

tetraidrofolico Questo acido egrave essenziale per la formazione delle purine e pirimidine componenti del DNA ed RNA Il

tetraidofolato egrave coinvolto anche nella sintesi di aminoacidi quali serina e metionina

La sua tossicitagrave egrave a carico di cellule ad alta velocitagrave di duplicazione quali quelle del midollo della pelle e dei capelli

Leuk Lymphoma 2011 Oct52(10)1882-90 Epub 2011 Jun 12High-dose methotrexate based chemotherapy with deferred radiation for treatment of newly diagnosed primary central nervous system lymphomaGerard LM Imrie KR Mangel J Buckstein R Doherty M Mackenzie R Cheung MCOdette Cancer Centre Sunnybrook Health Sciences Centre Toronto Ontario CanadaAbstractThe addition of high-dose methotrexate (HD-MTX) to whole-brain radiation therapy (WBRT) has improved the survival of patients with primary central nervous system lymphoma (PCNSL) However combined therapy is associated with increased neurotoxicity In an effort to limit this toxicity we treated a series of non-immunocompromised patients with HDMVP a HD-MTX based regimen with deferral of WBRT until progression Twenty-three patients were treated with the HDMVP regimen consisting of MTX vincristine and procarbazine The mean age at diagnosis was 609 years (range 45-79 years) The overall response rate was 65 (14 complete responses and one partial response) For patients achieving an initial response with HDMVP the median response duration was 404 months (95 confidence interval [CI] 195-613) The median progression-free survival was 46 months (95 CI 00-204) and median overall survival was 414 months (95 CI 00-955) Fourteen patients received WBRT for relapsed or progressive disease The conclusion of this trial is that HDVMP results in good initial response rates but only moderate disease control Ultimately the majority of the patients in this series required WBRT for salvage treatment potentially enabling a delay in treatment-associated neurotoxicityPMID 21663504 [PubMed - in process]

Idrazine

Procarbazina

Tiazine

Dacarbazina Tiotepa

Aziridine

La dacarbazina egrave un agente alchilante usata nel melanoma maligno nel linfoma di Hodgkin nei sarcomi e nei carcinomi del pancreas

Meccanismo di azione degli agenti alchilanti

Gli agenti alchilanti si legano con molte molecole intracellulari tra cui gli acidi

nucleici impedendone la lettura e quindi la trascrizione La citotossicitagrave egrave

primariamente dovuta al legame crociato tra filamenti di DNA ed RNA cosigrave

come allrsquoinibizione della sintesi proteica

Il busulfano egrave il solo agente usato nei regimi di mielosoppressione nei trapianti di cellule staminali ematopoietiche per la quale il monitoraggio terapeutico del farmaco egrave largamente usato Lrsquouso di busulfano per via orale porta ad una grande variabilitagrave intrapaziente e interpaziente in termini farmacocinetici specialmente nei bambini e lrsquoaggiustamento delle dosi egrave necessario per una ridotta tossicitagrave e migliore riuscita terapeutica Lrsquouso di busulfano per via endovenosa sta prendendo piede in quando porta a dei profili farmacocinetici piugrave controllabili La meningite neoplasica rappresenta il 5 dei tumori Ersquo una malattia che colpisce lrsquointero neuroasse e i farmaci devono passare nel fluido cefalorachidiano Oggigiorno la terapia con farmaci direttamente immessi nel liquido cefalorachidiano egrave ristretta a tre farmaci Il metotressato la citarabina ed il tiotepa Il cis-platino egrave un antitumorale usato per trattare vari tipi di cancro tipo sarcoma carcinosarcomi (piccolo cellule del polmone cancro ovarico) linfomi Ersquo il primo di una classe che va in crescendo di nuovi composti quali il carboplatino lrsquooxaliplatino Questi composti formano dei complessi allrsquointerno della cellula tumorale i quali legano il DNA attraverso legami intracatena e tra catene di DNA A questo segue lrsquoapoptosi cellulare

Although the entity we refer today as chronic myeloid leukemia (CML) was probably first described in the early nineteenth century there was little progress in understanding its biology until the discovery of the Philadelphia (Ph) chromosome in 19601 Subsequent important landmarks were the recognition that the Ph chromosome results from a t(922) translocation the demonstration that the leukemia probably originates from a single hematopoietic ldquostem cellrdquo the identification of the breakpoint cluster region (BCR) on chromosome no 22 and subsequently of the BCR-ABL fusion gene and more recently thedevelopment of a murine model simulating the human disease23 Treatment in the 19th century was unsatisfactory although arsenicals induced some degree of symptomatic control In the early 20th century radiotherapy was helpful but it was replaced in the 1950s by busulfan which remained popular for some years despite the emerging suspicion that this alkylating agent might in fact predispose to progression to advanced-phase disease In due course hydroxycarbamide replaced busulfan but interferon-alfa the first agent to induce any degree of Ph-chromosome negativity in the bone marrow was introduced in the early 1980s and became the treatment of choice for patients not eligible for allogeneic stem cell transplantation Between 1980 and 2000 allografting despite the risks of morbidity and mortality was the recommended initial treatment for younger patients with HLA-matched donors Therapy has now been ldquorevolutionizedrdquo by the introduction of imatinib (imatinib mesylate IM) the original Abl tyrosine kinase inhibitor (TKI) which was used first in the clinic in 1998

(Blood 20071102828-2837)

Lrsquoosteosarcoma egrave un cancro a carico dellrsquoosso e generalmente colpisce le ossa grandi delle braccia e delle gambe Ersquo presente frequentemente in giovani e sopratutto nei maschi La prognosi dellrsquo osteosarcoma degli arti trattata con solo amputazione puograve essere migliorata drammaticamente includendo la chemioterapia La chemioterapia neoadiuvante egrave comunemente usata per eradicare le micrometastasi e per preparare gli arti alla chirurgia di salvataggioOggi giorno una chirurgia conservativa egrave possibile nella maggior parte dei pazienti incluso i bambini ed egrave anche libera da recidive nei casi di sopravvivenza nel 50-80 Alte dosi di metotressato doxorubicina cis-platino ed ifosfamide sono considerate i

farmaci piugrave attivi contro lrsquoosteosarcoma Bull Cancer 2006 Nov 193(11)1115-20

Definizione del linfoma di Hodgkin Un cancro del sistema immunitario nel quale si evidenzia la presenza di un tipo particolare di cellule dette Reed-Sternberg cell I due tipi principali di linfoma di Hodgkin sono il classico e il nodulare che rappresenta il principale I sintomi includono dolore e ingrossamento dei linfonodi della milza o altri tessuti immunitari Altri sintomi includono febbre perdita di peso fatica e sudorazione notturna

Definizione di linfoma non-Hodgkin Rappresenta una versione di cancro al sistema immunitario (linfociti) Il linfoma non-Hodgkin egrave presente a qualsiasi etagrave e spesso egrave caratterizzato da ingrossamento dei linfonodi febbre e perdita di peso Ci sono diversi tipi di linfoma non-Hodgkin i quali possono essere suddivisi in aggressive (a crescita veloce) e indolenti ( a crescita lenta e possono essere classificati in linfomi delle cellule B o delle cellule T Tra i linfomi delle cellule B ricordiamo il linfoma di Burkitt linfomi diffusi delle cellule B linfomi follicolari linfomi immunoblastici a cellule grandi linfomi di precursori delle cellule B e linfomi di cellule mantello Linfomi non-Hodgkin delle cellule T includono micosi funginee linfomi anaplastici a cellule grandi e linfomi di precursori delle cellule T Linfomi correlati a disordini linfoproliferativi presenti a seguito di trapianti di midollo osseo o di cellule staminali generalmente sono linfomi non-hodgkin di cellule B

Reed-Sternberg cell

ANTIMETABOLITI

1) Analoghi dellrsquoacido folico

2) Analoghi delle purine

3) Analoghi delle pirimidine

Analoghi dellrsquoacido folico

Analoghi dellrsquoacido folico

METOTREXATOIl metotrexato egrave un analogo dellrsquoacido folico e inibisce la diidrofolico reduttasi prevenendo la formazione dellrsquoacido

tetraidrofolico Questo acido egrave essenziale per la formazione delle purine e pirimidine componenti del DNA ed RNA Il

tetraidofolato egrave coinvolto anche nella sintesi di aminoacidi quali serina e metionina

La sua tossicitagrave egrave a carico di cellule ad alta velocitagrave di duplicazione quali quelle del midollo della pelle e dei capelli

Leuk Lymphoma 2011 Oct52(10)1882-90 Epub 2011 Jun 12High-dose methotrexate based chemotherapy with deferred radiation for treatment of newly diagnosed primary central nervous system lymphomaGerard LM Imrie KR Mangel J Buckstein R Doherty M Mackenzie R Cheung MCOdette Cancer Centre Sunnybrook Health Sciences Centre Toronto Ontario CanadaAbstractThe addition of high-dose methotrexate (HD-MTX) to whole-brain radiation therapy (WBRT) has improved the survival of patients with primary central nervous system lymphoma (PCNSL) However combined therapy is associated with increased neurotoxicity In an effort to limit this toxicity we treated a series of non-immunocompromised patients with HDMVP a HD-MTX based regimen with deferral of WBRT until progression Twenty-three patients were treated with the HDMVP regimen consisting of MTX vincristine and procarbazine The mean age at diagnosis was 609 years (range 45-79 years) The overall response rate was 65 (14 complete responses and one partial response) For patients achieving an initial response with HDMVP the median response duration was 404 months (95 confidence interval [CI] 195-613) The median progression-free survival was 46 months (95 CI 00-204) and median overall survival was 414 months (95 CI 00-955) Fourteen patients received WBRT for relapsed or progressive disease The conclusion of this trial is that HDVMP results in good initial response rates but only moderate disease control Ultimately the majority of the patients in this series required WBRT for salvage treatment potentially enabling a delay in treatment-associated neurotoxicityPMID 21663504 [PubMed - in process]

Meccanismo di azione degli agenti alchilanti

Gli agenti alchilanti si legano con molte molecole intracellulari tra cui gli acidi

nucleici impedendone la lettura e quindi la trascrizione La citotossicitagrave egrave

primariamente dovuta al legame crociato tra filamenti di DNA ed RNA cosigrave

come allrsquoinibizione della sintesi proteica

Il busulfano egrave il solo agente usato nei regimi di mielosoppressione nei trapianti di cellule staminali ematopoietiche per la quale il monitoraggio terapeutico del farmaco egrave largamente usato Lrsquouso di busulfano per via orale porta ad una grande variabilitagrave intrapaziente e interpaziente in termini farmacocinetici specialmente nei bambini e lrsquoaggiustamento delle dosi egrave necessario per una ridotta tossicitagrave e migliore riuscita terapeutica Lrsquouso di busulfano per via endovenosa sta prendendo piede in quando porta a dei profili farmacocinetici piugrave controllabili La meningite neoplasica rappresenta il 5 dei tumori Ersquo una malattia che colpisce lrsquointero neuroasse e i farmaci devono passare nel fluido cefalorachidiano Oggigiorno la terapia con farmaci direttamente immessi nel liquido cefalorachidiano egrave ristretta a tre farmaci Il metotressato la citarabina ed il tiotepa Il cis-platino egrave un antitumorale usato per trattare vari tipi di cancro tipo sarcoma carcinosarcomi (piccolo cellule del polmone cancro ovarico) linfomi Ersquo il primo di una classe che va in crescendo di nuovi composti quali il carboplatino lrsquooxaliplatino Questi composti formano dei complessi allrsquointerno della cellula tumorale i quali legano il DNA attraverso legami intracatena e tra catene di DNA A questo segue lrsquoapoptosi cellulare

Although the entity we refer today as chronic myeloid leukemia (CML) was probably first described in the early nineteenth century there was little progress in understanding its biology until the discovery of the Philadelphia (Ph) chromosome in 19601 Subsequent important landmarks were the recognition that the Ph chromosome results from a t(922) translocation the demonstration that the leukemia probably originates from a single hematopoietic ldquostem cellrdquo the identification of the breakpoint cluster region (BCR) on chromosome no 22 and subsequently of the BCR-ABL fusion gene and more recently thedevelopment of a murine model simulating the human disease23 Treatment in the 19th century was unsatisfactory although arsenicals induced some degree of symptomatic control In the early 20th century radiotherapy was helpful but it was replaced in the 1950s by busulfan which remained popular for some years despite the emerging suspicion that this alkylating agent might in fact predispose to progression to advanced-phase disease In due course hydroxycarbamide replaced busulfan but interferon-alfa the first agent to induce any degree of Ph-chromosome negativity in the bone marrow was introduced in the early 1980s and became the treatment of choice for patients not eligible for allogeneic stem cell transplantation Between 1980 and 2000 allografting despite the risks of morbidity and mortality was the recommended initial treatment for younger patients with HLA-matched donors Therapy has now been ldquorevolutionizedrdquo by the introduction of imatinib (imatinib mesylate IM) the original Abl tyrosine kinase inhibitor (TKI) which was used first in the clinic in 1998

(Blood 20071102828-2837)

Lrsquoosteosarcoma egrave un cancro a carico dellrsquoosso e generalmente colpisce le ossa grandi delle braccia e delle gambe Ersquo presente frequentemente in giovani e sopratutto nei maschi La prognosi dellrsquo osteosarcoma degli arti trattata con solo amputazione puograve essere migliorata drammaticamente includendo la chemioterapia La chemioterapia neoadiuvante egrave comunemente usata per eradicare le micrometastasi e per preparare gli arti alla chirurgia di salvataggioOggi giorno una chirurgia conservativa egrave possibile nella maggior parte dei pazienti incluso i bambini ed egrave anche libera da recidive nei casi di sopravvivenza nel 50-80 Alte dosi di metotressato doxorubicina cis-platino ed ifosfamide sono considerate i

farmaci piugrave attivi contro lrsquoosteosarcoma Bull Cancer 2006 Nov 193(11)1115-20

Definizione del linfoma di Hodgkin Un cancro del sistema immunitario nel quale si evidenzia la presenza di un tipo particolare di cellule dette Reed-Sternberg cell I due tipi principali di linfoma di Hodgkin sono il classico e il nodulare che rappresenta il principale I sintomi includono dolore e ingrossamento dei linfonodi della milza o altri tessuti immunitari Altri sintomi includono febbre perdita di peso fatica e sudorazione notturna

Definizione di linfoma non-Hodgkin Rappresenta una versione di cancro al sistema immunitario (linfociti) Il linfoma non-Hodgkin egrave presente a qualsiasi etagrave e spesso egrave caratterizzato da ingrossamento dei linfonodi febbre e perdita di peso Ci sono diversi tipi di linfoma non-Hodgkin i quali possono essere suddivisi in aggressive (a crescita veloce) e indolenti ( a crescita lenta e possono essere classificati in linfomi delle cellule B o delle cellule T Tra i linfomi delle cellule B ricordiamo il linfoma di Burkitt linfomi diffusi delle cellule B linfomi follicolari linfomi immunoblastici a cellule grandi linfomi di precursori delle cellule B e linfomi di cellule mantello Linfomi non-Hodgkin delle cellule T includono micosi funginee linfomi anaplastici a cellule grandi e linfomi di precursori delle cellule T Linfomi correlati a disordini linfoproliferativi presenti a seguito di trapianti di midollo osseo o di cellule staminali generalmente sono linfomi non-hodgkin di cellule B

Reed-Sternberg cell

ANTIMETABOLITI

1) Analoghi dellrsquoacido folico

2) Analoghi delle purine

3) Analoghi delle pirimidine

Analoghi dellrsquoacido folico

Analoghi dellrsquoacido folico

METOTREXATOIl metotrexato egrave un analogo dellrsquoacido folico e inibisce la diidrofolico reduttasi prevenendo la formazione dellrsquoacido

tetraidrofolico Questo acido egrave essenziale per la formazione delle purine e pirimidine componenti del DNA ed RNA Il

tetraidofolato egrave coinvolto anche nella sintesi di aminoacidi quali serina e metionina

La sua tossicitagrave egrave a carico di cellule ad alta velocitagrave di duplicazione quali quelle del midollo della pelle e dei capelli

Leuk Lymphoma 2011 Oct52(10)1882-90 Epub 2011 Jun 12High-dose methotrexate based chemotherapy with deferred radiation for treatment of newly diagnosed primary central nervous system lymphomaGerard LM Imrie KR Mangel J Buckstein R Doherty M Mackenzie R Cheung MCOdette Cancer Centre Sunnybrook Health Sciences Centre Toronto Ontario CanadaAbstractThe addition of high-dose methotrexate (HD-MTX) to whole-brain radiation therapy (WBRT) has improved the survival of patients with primary central nervous system lymphoma (PCNSL) However combined therapy is associated with increased neurotoxicity In an effort to limit this toxicity we treated a series of non-immunocompromised patients with HDMVP a HD-MTX based regimen with deferral of WBRT until progression Twenty-three patients were treated with the HDMVP regimen consisting of MTX vincristine and procarbazine The mean age at diagnosis was 609 years (range 45-79 years) The overall response rate was 65 (14 complete responses and one partial response) For patients achieving an initial response with HDMVP the median response duration was 404 months (95 confidence interval [CI] 195-613) The median progression-free survival was 46 months (95 CI 00-204) and median overall survival was 414 months (95 CI 00-955) Fourteen patients received WBRT for relapsed or progressive disease The conclusion of this trial is that HDVMP results in good initial response rates but only moderate disease control Ultimately the majority of the patients in this series required WBRT for salvage treatment potentially enabling a delay in treatment-associated neurotoxicityPMID 21663504 [PubMed - in process]

Il busulfano egrave il solo agente usato nei regimi di mielosoppressione nei trapianti di cellule staminali ematopoietiche per la quale il monitoraggio terapeutico del farmaco egrave largamente usato Lrsquouso di busulfano per via orale porta ad una grande variabilitagrave intrapaziente e interpaziente in termini farmacocinetici specialmente nei bambini e lrsquoaggiustamento delle dosi egrave necessario per una ridotta tossicitagrave e migliore riuscita terapeutica Lrsquouso di busulfano per via endovenosa sta prendendo piede in quando porta a dei profili farmacocinetici piugrave controllabili La meningite neoplasica rappresenta il 5 dei tumori Ersquo una malattia che colpisce lrsquointero neuroasse e i farmaci devono passare nel fluido cefalorachidiano Oggigiorno la terapia con farmaci direttamente immessi nel liquido cefalorachidiano egrave ristretta a tre farmaci Il metotressato la citarabina ed il tiotepa Il cis-platino egrave un antitumorale usato per trattare vari tipi di cancro tipo sarcoma carcinosarcomi (piccolo cellule del polmone cancro ovarico) linfomi Ersquo il primo di una classe che va in crescendo di nuovi composti quali il carboplatino lrsquooxaliplatino Questi composti formano dei complessi allrsquointerno della cellula tumorale i quali legano il DNA attraverso legami intracatena e tra catene di DNA A questo segue lrsquoapoptosi cellulare

Although the entity we refer today as chronic myeloid leukemia (CML) was probably first described in the early nineteenth century there was little progress in understanding its biology until the discovery of the Philadelphia (Ph) chromosome in 19601 Subsequent important landmarks were the recognition that the Ph chromosome results from a t(922) translocation the demonstration that the leukemia probably originates from a single hematopoietic ldquostem cellrdquo the identification of the breakpoint cluster region (BCR) on chromosome no 22 and subsequently of the BCR-ABL fusion gene and more recently thedevelopment of a murine model simulating the human disease23 Treatment in the 19th century was unsatisfactory although arsenicals induced some degree of symptomatic control In the early 20th century radiotherapy was helpful but it was replaced in the 1950s by busulfan which remained popular for some years despite the emerging suspicion that this alkylating agent might in fact predispose to progression to advanced-phase disease In due course hydroxycarbamide replaced busulfan but interferon-alfa the first agent to induce any degree of Ph-chromosome negativity in the bone marrow was introduced in the early 1980s and became the treatment of choice for patients not eligible for allogeneic stem cell transplantation Between 1980 and 2000 allografting despite the risks of morbidity and mortality was the recommended initial treatment for younger patients with HLA-matched donors Therapy has now been ldquorevolutionizedrdquo by the introduction of imatinib (imatinib mesylate IM) the original Abl tyrosine kinase inhibitor (TKI) which was used first in the clinic in 1998

(Blood 20071102828-2837)

Lrsquoosteosarcoma egrave un cancro a carico dellrsquoosso e generalmente colpisce le ossa grandi delle braccia e delle gambe Ersquo presente frequentemente in giovani e sopratutto nei maschi La prognosi dellrsquo osteosarcoma degli arti trattata con solo amputazione puograve essere migliorata drammaticamente includendo la chemioterapia La chemioterapia neoadiuvante egrave comunemente usata per eradicare le micrometastasi e per preparare gli arti alla chirurgia di salvataggioOggi giorno una chirurgia conservativa egrave possibile nella maggior parte dei pazienti incluso i bambini ed egrave anche libera da recidive nei casi di sopravvivenza nel 50-80 Alte dosi di metotressato doxorubicina cis-platino ed ifosfamide sono considerate i

farmaci piugrave attivi contro lrsquoosteosarcoma Bull Cancer 2006 Nov 193(11)1115-20

Definizione del linfoma di Hodgkin Un cancro del sistema immunitario nel quale si evidenzia la presenza di un tipo particolare di cellule dette Reed-Sternberg cell I due tipi principali di linfoma di Hodgkin sono il classico e il nodulare che rappresenta il principale I sintomi includono dolore e ingrossamento dei linfonodi della milza o altri tessuti immunitari Altri sintomi includono febbre perdita di peso fatica e sudorazione notturna

Definizione di linfoma non-Hodgkin Rappresenta una versione di cancro al sistema immunitario (linfociti) Il linfoma non-Hodgkin egrave presente a qualsiasi etagrave e spesso egrave caratterizzato da ingrossamento dei linfonodi febbre e perdita di peso Ci sono diversi tipi di linfoma non-Hodgkin i quali possono essere suddivisi in aggressive (a crescita veloce) e indolenti ( a crescita lenta e possono essere classificati in linfomi delle cellule B o delle cellule T Tra i linfomi delle cellule B ricordiamo il linfoma di Burkitt linfomi diffusi delle cellule B linfomi follicolari linfomi immunoblastici a cellule grandi linfomi di precursori delle cellule B e linfomi di cellule mantello Linfomi non-Hodgkin delle cellule T includono micosi funginee linfomi anaplastici a cellule grandi e linfomi di precursori delle cellule T Linfomi correlati a disordini linfoproliferativi presenti a seguito di trapianti di midollo osseo o di cellule staminali generalmente sono linfomi non-hodgkin di cellule B

Reed-Sternberg cell

ANTIMETABOLITI

1) Analoghi dellrsquoacido folico

2) Analoghi delle purine

3) Analoghi delle pirimidine

Analoghi dellrsquoacido folico

Analoghi dellrsquoacido folico

METOTREXATOIl metotrexato egrave un analogo dellrsquoacido folico e inibisce la diidrofolico reduttasi prevenendo la formazione dellrsquoacido

tetraidrofolico Questo acido egrave essenziale per la formazione delle purine e pirimidine componenti del DNA ed RNA Il

tetraidofolato egrave coinvolto anche nella sintesi di aminoacidi quali serina e metionina

La sua tossicitagrave egrave a carico di cellule ad alta velocitagrave di duplicazione quali quelle del midollo della pelle e dei capelli

Leuk Lymphoma 2011 Oct52(10)1882-90 Epub 2011 Jun 12High-dose methotrexate based chemotherapy with deferred radiation for treatment of newly diagnosed primary central nervous system lymphomaGerard LM Imrie KR Mangel J Buckstein R Doherty M Mackenzie R Cheung MCOdette Cancer Centre Sunnybrook Health Sciences Centre Toronto Ontario CanadaAbstractThe addition of high-dose methotrexate (HD-MTX) to whole-brain radiation therapy (WBRT) has improved the survival of patients with primary central nervous system lymphoma (PCNSL) However combined therapy is associated with increased neurotoxicity In an effort to limit this toxicity we treated a series of non-immunocompromised patients with HDMVP a HD-MTX based regimen with deferral of WBRT until progression Twenty-three patients were treated with the HDMVP regimen consisting of MTX vincristine and procarbazine The mean age at diagnosis was 609 years (range 45-79 years) The overall response rate was 65 (14 complete responses and one partial response) For patients achieving an initial response with HDMVP the median response duration was 404 months (95 confidence interval [CI] 195-613) The median progression-free survival was 46 months (95 CI 00-204) and median overall survival was 414 months (95 CI 00-955) Fourteen patients received WBRT for relapsed or progressive disease The conclusion of this trial is that HDVMP results in good initial response rates but only moderate disease control Ultimately the majority of the patients in this series required WBRT for salvage treatment potentially enabling a delay in treatment-associated neurotoxicityPMID 21663504 [PubMed - in process]

Although the entity we refer today as chronic myeloid leukemia (CML) was probably first described in the early nineteenth century there was little progress in understanding its biology until the discovery of the Philadelphia (Ph) chromosome in 19601 Subsequent important landmarks were the recognition that the Ph chromosome results from a t(922) translocation the demonstration that the leukemia probably originates from a single hematopoietic ldquostem cellrdquo the identification of the breakpoint cluster region (BCR) on chromosome no 22 and subsequently of the BCR-ABL fusion gene and more recently thedevelopment of a murine model simulating the human disease23 Treatment in the 19th century was unsatisfactory although arsenicals induced some degree of symptomatic control In the early 20th century radiotherapy was helpful but it was replaced in the 1950s by busulfan which remained popular for some years despite the emerging suspicion that this alkylating agent might in fact predispose to progression to advanced-phase disease In due course hydroxycarbamide replaced busulfan but interferon-alfa the first agent to induce any degree of Ph-chromosome negativity in the bone marrow was introduced in the early 1980s and became the treatment of choice for patients not eligible for allogeneic stem cell transplantation Between 1980 and 2000 allografting despite the risks of morbidity and mortality was the recommended initial treatment for younger patients with HLA-matched donors Therapy has now been ldquorevolutionizedrdquo by the introduction of imatinib (imatinib mesylate IM) the original Abl tyrosine kinase inhibitor (TKI) which was used first in the clinic in 1998

(Blood 20071102828-2837)

Lrsquoosteosarcoma egrave un cancro a carico dellrsquoosso e generalmente colpisce le ossa grandi delle braccia e delle gambe Ersquo presente frequentemente in giovani e sopratutto nei maschi La prognosi dellrsquo osteosarcoma degli arti trattata con solo amputazione puograve essere migliorata drammaticamente includendo la chemioterapia La chemioterapia neoadiuvante egrave comunemente usata per eradicare le micrometastasi e per preparare gli arti alla chirurgia di salvataggioOggi giorno una chirurgia conservativa egrave possibile nella maggior parte dei pazienti incluso i bambini ed egrave anche libera da recidive nei casi di sopravvivenza nel 50-80 Alte dosi di metotressato doxorubicina cis-platino ed ifosfamide sono considerate i

farmaci piugrave attivi contro lrsquoosteosarcoma Bull Cancer 2006 Nov 193(11)1115-20

Definizione del linfoma di Hodgkin Un cancro del sistema immunitario nel quale si evidenzia la presenza di un tipo particolare di cellule dette Reed-Sternberg cell I due tipi principali di linfoma di Hodgkin sono il classico e il nodulare che rappresenta il principale I sintomi includono dolore e ingrossamento dei linfonodi della milza o altri tessuti immunitari Altri sintomi includono febbre perdita di peso fatica e sudorazione notturna

Definizione di linfoma non-Hodgkin Rappresenta una versione di cancro al sistema immunitario (linfociti) Il linfoma non-Hodgkin egrave presente a qualsiasi etagrave e spesso egrave caratterizzato da ingrossamento dei linfonodi febbre e perdita di peso Ci sono diversi tipi di linfoma non-Hodgkin i quali possono essere suddivisi in aggressive (a crescita veloce) e indolenti ( a crescita lenta e possono essere classificati in linfomi delle cellule B o delle cellule T Tra i linfomi delle cellule B ricordiamo il linfoma di Burkitt linfomi diffusi delle cellule B linfomi follicolari linfomi immunoblastici a cellule grandi linfomi di precursori delle cellule B e linfomi di cellule mantello Linfomi non-Hodgkin delle cellule T includono micosi funginee linfomi anaplastici a cellule grandi e linfomi di precursori delle cellule T Linfomi correlati a disordini linfoproliferativi presenti a seguito di trapianti di midollo osseo o di cellule staminali generalmente sono linfomi non-hodgkin di cellule B

Reed-Sternberg cell

ANTIMETABOLITI

1) Analoghi dellrsquoacido folico

2) Analoghi delle purine

3) Analoghi delle pirimidine

Analoghi dellrsquoacido folico

Analoghi dellrsquoacido folico

METOTREXATOIl metotrexato egrave un analogo dellrsquoacido folico e inibisce la diidrofolico reduttasi prevenendo la formazione dellrsquoacido

tetraidrofolico Questo acido egrave essenziale per la formazione delle purine e pirimidine componenti del DNA ed RNA Il

tetraidofolato egrave coinvolto anche nella sintesi di aminoacidi quali serina e metionina

La sua tossicitagrave egrave a carico di cellule ad alta velocitagrave di duplicazione quali quelle del midollo della pelle e dei capelli

Leuk Lymphoma 2011 Oct52(10)1882-90 Epub 2011 Jun 12High-dose methotrexate based chemotherapy with deferred radiation for treatment of newly diagnosed primary central nervous system lymphomaGerard LM Imrie KR Mangel J Buckstein R Doherty M Mackenzie R Cheung MCOdette Cancer Centre Sunnybrook Health Sciences Centre Toronto Ontario CanadaAbstractThe addition of high-dose methotrexate (HD-MTX) to whole-brain radiation therapy (WBRT) has improved the survival of patients with primary central nervous system lymphoma (PCNSL) However combined therapy is associated with increased neurotoxicity In an effort to limit this toxicity we treated a series of non-immunocompromised patients with HDMVP a HD-MTX based regimen with deferral of WBRT until progression Twenty-three patients were treated with the HDMVP regimen consisting of MTX vincristine and procarbazine The mean age at diagnosis was 609 years (range 45-79 years) The overall response rate was 65 (14 complete responses and one partial response) For patients achieving an initial response with HDMVP the median response duration was 404 months (95 confidence interval [CI] 195-613) The median progression-free survival was 46 months (95 CI 00-204) and median overall survival was 414 months (95 CI 00-955) Fourteen patients received WBRT for relapsed or progressive disease The conclusion of this trial is that HDVMP results in good initial response rates but only moderate disease control Ultimately the majority of the patients in this series required WBRT for salvage treatment potentially enabling a delay in treatment-associated neurotoxicityPMID 21663504 [PubMed - in process]

Lrsquoosteosarcoma egrave un cancro a carico dellrsquoosso e generalmente colpisce le ossa grandi delle braccia e delle gambe Ersquo presente frequentemente in giovani e sopratutto nei maschi La prognosi dellrsquo osteosarcoma degli arti trattata con solo amputazione puograve essere migliorata drammaticamente includendo la chemioterapia La chemioterapia neoadiuvante egrave comunemente usata per eradicare le micrometastasi e per preparare gli arti alla chirurgia di salvataggioOggi giorno una chirurgia conservativa egrave possibile nella maggior parte dei pazienti incluso i bambini ed egrave anche libera da recidive nei casi di sopravvivenza nel 50-80 Alte dosi di metotressato doxorubicina cis-platino ed ifosfamide sono considerate i

farmaci piugrave attivi contro lrsquoosteosarcoma Bull Cancer 2006 Nov 193(11)1115-20

Definizione del linfoma di Hodgkin Un cancro del sistema immunitario nel quale si evidenzia la presenza di un tipo particolare di cellule dette Reed-Sternberg cell I due tipi principali di linfoma di Hodgkin sono il classico e il nodulare che rappresenta il principale I sintomi includono dolore e ingrossamento dei linfonodi della milza o altri tessuti immunitari Altri sintomi includono febbre perdita di peso fatica e sudorazione notturna

Definizione di linfoma non-Hodgkin Rappresenta una versione di cancro al sistema immunitario (linfociti) Il linfoma non-Hodgkin egrave presente a qualsiasi etagrave e spesso egrave caratterizzato da ingrossamento dei linfonodi febbre e perdita di peso Ci sono diversi tipi di linfoma non-Hodgkin i quali possono essere suddivisi in aggressive (a crescita veloce) e indolenti ( a crescita lenta e possono essere classificati in linfomi delle cellule B o delle cellule T Tra i linfomi delle cellule B ricordiamo il linfoma di Burkitt linfomi diffusi delle cellule B linfomi follicolari linfomi immunoblastici a cellule grandi linfomi di precursori delle cellule B e linfomi di cellule mantello Linfomi non-Hodgkin delle cellule T includono micosi funginee linfomi anaplastici a cellule grandi e linfomi di precursori delle cellule T Linfomi correlati a disordini linfoproliferativi presenti a seguito di trapianti di midollo osseo o di cellule staminali generalmente sono linfomi non-hodgkin di cellule B

Reed-Sternberg cell

ANTIMETABOLITI

1) Analoghi dellrsquoacido folico

2) Analoghi delle purine

3) Analoghi delle pirimidine

Analoghi dellrsquoacido folico

Analoghi dellrsquoacido folico

METOTREXATOIl metotrexato egrave un analogo dellrsquoacido folico e inibisce la diidrofolico reduttasi prevenendo la formazione dellrsquoacido

tetraidrofolico Questo acido egrave essenziale per la formazione delle purine e pirimidine componenti del DNA ed RNA Il

tetraidofolato egrave coinvolto anche nella sintesi di aminoacidi quali serina e metionina

La sua tossicitagrave egrave a carico di cellule ad alta velocitagrave di duplicazione quali quelle del midollo della pelle e dei capelli

Leuk Lymphoma 2011 Oct52(10)1882-90 Epub 2011 Jun 12High-dose methotrexate based chemotherapy with deferred radiation for treatment of newly diagnosed primary central nervous system lymphomaGerard LM Imrie KR Mangel J Buckstein R Doherty M Mackenzie R Cheung MCOdette Cancer Centre Sunnybrook Health Sciences Centre Toronto Ontario CanadaAbstractThe addition of high-dose methotrexate (HD-MTX) to whole-brain radiation therapy (WBRT) has improved the survival of patients with primary central nervous system lymphoma (PCNSL) However combined therapy is associated with increased neurotoxicity In an effort to limit this toxicity we treated a series of non-immunocompromised patients with HDMVP a HD-MTX based regimen with deferral of WBRT until progression Twenty-three patients were treated with the HDMVP regimen consisting of MTX vincristine and procarbazine The mean age at diagnosis was 609 years (range 45-79 years) The overall response rate was 65 (14 complete responses and one partial response) For patients achieving an initial response with HDMVP the median response duration was 404 months (95 confidence interval [CI] 195-613) The median progression-free survival was 46 months (95 CI 00-204) and median overall survival was 414 months (95 CI 00-955) Fourteen patients received WBRT for relapsed or progressive disease The conclusion of this trial is that HDVMP results in good initial response rates but only moderate disease control Ultimately the majority of the patients in this series required WBRT for salvage treatment potentially enabling a delay in treatment-associated neurotoxicityPMID 21663504 [PubMed - in process]

Definizione del linfoma di Hodgkin Un cancro del sistema immunitario nel quale si evidenzia la presenza di un tipo particolare di cellule dette Reed-Sternberg cell I due tipi principali di linfoma di Hodgkin sono il classico e il nodulare che rappresenta il principale I sintomi includono dolore e ingrossamento dei linfonodi della milza o altri tessuti immunitari Altri sintomi includono febbre perdita di peso fatica e sudorazione notturna

Definizione di linfoma non-Hodgkin Rappresenta una versione di cancro al sistema immunitario (linfociti) Il linfoma non-Hodgkin egrave presente a qualsiasi etagrave e spesso egrave caratterizzato da ingrossamento dei linfonodi febbre e perdita di peso Ci sono diversi tipi di linfoma non-Hodgkin i quali possono essere suddivisi in aggressive (a crescita veloce) e indolenti ( a crescita lenta e possono essere classificati in linfomi delle cellule B o delle cellule T Tra i linfomi delle cellule B ricordiamo il linfoma di Burkitt linfomi diffusi delle cellule B linfomi follicolari linfomi immunoblastici a cellule grandi linfomi di precursori delle cellule B e linfomi di cellule mantello Linfomi non-Hodgkin delle cellule T includono micosi funginee linfomi anaplastici a cellule grandi e linfomi di precursori delle cellule T Linfomi correlati a disordini linfoproliferativi presenti a seguito di trapianti di midollo osseo o di cellule staminali generalmente sono linfomi non-hodgkin di cellule B

Reed-Sternberg cell

ANTIMETABOLITI

1) Analoghi dellrsquoacido folico

2) Analoghi delle purine

3) Analoghi delle pirimidine

Analoghi dellrsquoacido folico

Analoghi dellrsquoacido folico

METOTREXATOIl metotrexato egrave un analogo dellrsquoacido folico e inibisce la diidrofolico reduttasi prevenendo la formazione dellrsquoacido

tetraidrofolico Questo acido egrave essenziale per la formazione delle purine e pirimidine componenti del DNA ed RNA Il

tetraidofolato egrave coinvolto anche nella sintesi di aminoacidi quali serina e metionina

La sua tossicitagrave egrave a carico di cellule ad alta velocitagrave di duplicazione quali quelle del midollo della pelle e dei capelli

Leuk Lymphoma 2011 Oct52(10)1882-90 Epub 2011 Jun 12High-dose methotrexate based chemotherapy with deferred radiation for treatment of newly diagnosed primary central nervous system lymphomaGerard LM Imrie KR Mangel J Buckstein R Doherty M Mackenzie R Cheung MCOdette Cancer Centre Sunnybrook Health Sciences Centre Toronto Ontario CanadaAbstractThe addition of high-dose methotrexate (HD-MTX) to whole-brain radiation therapy (WBRT) has improved the survival of patients with primary central nervous system lymphoma (PCNSL) However combined therapy is associated with increased neurotoxicity In an effort to limit this toxicity we treated a series of non-immunocompromised patients with HDMVP a HD-MTX based regimen with deferral of WBRT until progression Twenty-three patients were treated with the HDMVP regimen consisting of MTX vincristine and procarbazine The mean age at diagnosis was 609 years (range 45-79 years) The overall response rate was 65 (14 complete responses and one partial response) For patients achieving an initial response with HDMVP the median response duration was 404 months (95 confidence interval [CI] 195-613) The median progression-free survival was 46 months (95 CI 00-204) and median overall survival was 414 months (95 CI 00-955) Fourteen patients received WBRT for relapsed or progressive disease The conclusion of this trial is that HDVMP results in good initial response rates but only moderate disease control Ultimately the majority of the patients in this series required WBRT for salvage treatment potentially enabling a delay in treatment-associated neurotoxicityPMID 21663504 [PubMed - in process]

Reed-Sternberg cell

ANTIMETABOLITI

1) Analoghi dellrsquoacido folico

2) Analoghi delle purine

3) Analoghi delle pirimidine

Analoghi dellrsquoacido folico

Analoghi dellrsquoacido folico

METOTREXATOIl metotrexato egrave un analogo dellrsquoacido folico e inibisce la diidrofolico reduttasi prevenendo la formazione dellrsquoacido

tetraidrofolico Questo acido egrave essenziale per la formazione delle purine e pirimidine componenti del DNA ed RNA Il

tetraidofolato egrave coinvolto anche nella sintesi di aminoacidi quali serina e metionina

La sua tossicitagrave egrave a carico di cellule ad alta velocitagrave di duplicazione quali quelle del midollo della pelle e dei capelli

Leuk Lymphoma 2011 Oct52(10)1882-90 Epub 2011 Jun 12High-dose methotrexate based chemotherapy with deferred radiation for treatment of newly diagnosed primary central nervous system lymphomaGerard LM Imrie KR Mangel J Buckstein R Doherty M Mackenzie R Cheung MCOdette Cancer Centre Sunnybrook Health Sciences Centre Toronto Ontario CanadaAbstractThe addition of high-dose methotrexate (HD-MTX) to whole-brain radiation therapy (WBRT) has improved the survival of patients with primary central nervous system lymphoma (PCNSL) However combined therapy is associated with increased neurotoxicity In an effort to limit this toxicity we treated a series of non-immunocompromised patients with HDMVP a HD-MTX based regimen with deferral of WBRT until progression Twenty-three patients were treated with the HDMVP regimen consisting of MTX vincristine and procarbazine The mean age at diagnosis was 609 years (range 45-79 years) The overall response rate was 65 (14 complete responses and one partial response) For patients achieving an initial response with HDMVP the median response duration was 404 months (95 confidence interval [CI] 195-613) The median progression-free survival was 46 months (95 CI 00-204) and median overall survival was 414 months (95 CI 00-955) Fourteen patients received WBRT for relapsed or progressive disease The conclusion of this trial is that HDVMP results in good initial response rates but only moderate disease control Ultimately the majority of the patients in this series required WBRT for salvage treatment potentially enabling a delay in treatment-associated neurotoxicityPMID 21663504 [PubMed - in process]

ANTIMETABOLITI

1) Analoghi dellrsquoacido folico

2) Analoghi delle purine

3) Analoghi delle pirimidine

Analoghi dellrsquoacido folico

Analoghi dellrsquoacido folico

METOTREXATOIl metotrexato egrave un analogo dellrsquoacido folico e inibisce la diidrofolico reduttasi prevenendo la formazione dellrsquoacido

tetraidrofolico Questo acido egrave essenziale per la formazione delle purine e pirimidine componenti del DNA ed RNA Il

tetraidofolato egrave coinvolto anche nella sintesi di aminoacidi quali serina e metionina

La sua tossicitagrave egrave a carico di cellule ad alta velocitagrave di duplicazione quali quelle del midollo della pelle e dei capelli

Leuk Lymphoma 2011 Oct52(10)1882-90 Epub 2011 Jun 12High-dose methotrexate based chemotherapy with deferred radiation for treatment of newly diagnosed primary central nervous system lymphomaGerard LM Imrie KR Mangel J Buckstein R Doherty M Mackenzie R Cheung MCOdette Cancer Centre Sunnybrook Health Sciences Centre Toronto Ontario CanadaAbstractThe addition of high-dose methotrexate (HD-MTX) to whole-brain radiation therapy (WBRT) has improved the survival of patients with primary central nervous system lymphoma (PCNSL) However combined therapy is associated with increased neurotoxicity In an effort to limit this toxicity we treated a series of non-immunocompromised patients with HDMVP a HD-MTX based regimen with deferral of WBRT until progression Twenty-three patients were treated with the HDMVP regimen consisting of MTX vincristine and procarbazine The mean age at diagnosis was 609 years (range 45-79 years) The overall response rate was 65 (14 complete responses and one partial response) For patients achieving an initial response with HDMVP the median response duration was 404 months (95 confidence interval [CI] 195-613) The median progression-free survival was 46 months (95 CI 00-204) and median overall survival was 414 months (95 CI 00-955) Fourteen patients received WBRT for relapsed or progressive disease The conclusion of this trial is that HDVMP results in good initial response rates but only moderate disease control Ultimately the majority of the patients in this series required WBRT for salvage treatment potentially enabling a delay in treatment-associated neurotoxicityPMID 21663504 [PubMed - in process]

Analoghi dellrsquoacido folico

Analoghi dellrsquoacido folico

METOTREXATOIl metotrexato egrave un analogo dellrsquoacido folico e inibisce la diidrofolico reduttasi prevenendo la formazione dellrsquoacido

tetraidrofolico Questo acido egrave essenziale per la formazione delle purine e pirimidine componenti del DNA ed RNA Il

tetraidofolato egrave coinvolto anche nella sintesi di aminoacidi quali serina e metionina

La sua tossicitagrave egrave a carico di cellule ad alta velocitagrave di duplicazione quali quelle del midollo della pelle e dei capelli

Leuk Lymphoma 2011 Oct52(10)1882-90 Epub 2011 Jun 12High-dose methotrexate based chemotherapy with deferred radiation for treatment of newly diagnosed primary central nervous system lymphomaGerard LM Imrie KR Mangel J Buckstein R Doherty M Mackenzie R Cheung MCOdette Cancer Centre Sunnybrook Health Sciences Centre Toronto Ontario CanadaAbstractThe addition of high-dose methotrexate (HD-MTX) to whole-brain radiation therapy (WBRT) has improved the survival of patients with primary central nervous system lymphoma (PCNSL) However combined therapy is associated with increased neurotoxicity In an effort to limit this toxicity we treated a series of non-immunocompromised patients with HDMVP a HD-MTX based regimen with deferral of WBRT until progression Twenty-three patients were treated with the HDMVP regimen consisting of MTX vincristine and procarbazine The mean age at diagnosis was 609 years (range 45-79 years) The overall response rate was 65 (14 complete responses and one partial response) For patients achieving an initial response with HDMVP the median response duration was 404 months (95 confidence interval [CI] 195-613) The median progression-free survival was 46 months (95 CI 00-204) and median overall survival was 414 months (95 CI 00-955) Fourteen patients received WBRT for relapsed or progressive disease The conclusion of this trial is that HDVMP results in good initial response rates but only moderate disease control Ultimately the majority of the patients in this series required WBRT for salvage treatment potentially enabling a delay in treatment-associated neurotoxicityPMID 21663504 [PubMed - in process]

Analoghi dellrsquoacido folico

METOTREXATOIl metotrexato egrave un analogo dellrsquoacido folico e inibisce la diidrofolico reduttasi prevenendo la formazione dellrsquoacido

tetraidrofolico Questo acido egrave essenziale per la formazione delle purine e pirimidine componenti del DNA ed RNA Il

tetraidofolato egrave coinvolto anche nella sintesi di aminoacidi quali serina e metionina

La sua tossicitagrave egrave a carico di cellule ad alta velocitagrave di duplicazione quali quelle del midollo della pelle e dei capelli

Leuk Lymphoma 2011 Oct52(10)1882-90 Epub 2011 Jun 12High-dose methotrexate based chemotherapy with deferred radiation for treatment of newly diagnosed primary central nervous system lymphomaGerard LM Imrie KR Mangel J Buckstein R Doherty M Mackenzie R Cheung MCOdette Cancer Centre Sunnybrook Health Sciences Centre Toronto Ontario CanadaAbstractThe addition of high-dose methotrexate (HD-MTX) to whole-brain radiation therapy (WBRT) has improved the survival of patients with primary central nervous system lymphoma (PCNSL) However combined therapy is associated with increased neurotoxicity In an effort to limit this toxicity we treated a series of non-immunocompromised patients with HDMVP a HD-MTX based regimen with deferral of WBRT until progression Twenty-three patients were treated with the HDMVP regimen consisting of MTX vincristine and procarbazine The mean age at diagnosis was 609 years (range 45-79 years) The overall response rate was 65 (14 complete responses and one partial response) For patients achieving an initial response with HDMVP the median response duration was 404 months (95 confidence interval [CI] 195-613) The median progression-free survival was 46 months (95 CI 00-204) and median overall survival was 414 months (95 CI 00-955) Fourteen patients received WBRT for relapsed or progressive disease The conclusion of this trial is that HDVMP results in good initial response rates but only moderate disease control Ultimately the majority of the patients in this series required WBRT for salvage treatment potentially enabling a delay in treatment-associated neurotoxicityPMID 21663504 [PubMed - in process]

Leuk Lymphoma 2011 Oct52(10)1882-90 Epub 2011 Jun 12High-dose methotrexate based chemotherapy with deferred radiation for treatment of newly diagnosed primary central nervous system lymphomaGerard LM Imrie KR Mangel J Buckstein R Doherty M Mackenzie R Cheung MCOdette Cancer Centre Sunnybrook Health Sciences Centre Toronto Ontario CanadaAbstractThe addition of high-dose methotrexate (HD-MTX) to whole-brain radiation therapy (WBRT) has improved the survival of patients with primary central nervous system lymphoma (PCNSL) However combined therapy is associated with increased neurotoxicity In an effort to limit this toxicity we treated a series of non-immunocompromised patients with HDMVP a HD-MTX based regimen with deferral of WBRT until progression Twenty-three patients were treated with the HDMVP regimen consisting of MTX vincristine and procarbazine The mean age at diagnosis was 609 years (range 45-79 years) The overall response rate was 65 (14 complete responses and one partial response) For patients achieving an initial response with HDMVP the median response duration was 404 months (95 confidence interval [CI] 195-613) The median progression-free survival was 46 months (95 CI 00-204) and median overall survival was 414 months (95 CI 00-955) Fourteen patients received WBRT for relapsed or progressive disease The conclusion of this trial is that HDVMP results in good initial response rates but only moderate disease control Ultimately the majority of the patients in this series required WBRT for salvage treatment potentially enabling a delay in treatment-associated neurotoxicityPMID 21663504 [PubMed - in process]

Prog Urol 2011 Jun21(6)369-82 doi 101016jpurol201102005 Epub 2011 Mar 29

[The role of chemotherapy in the management of bladder cancer][Article in French]Ismaili N Amzerin M Elmajjaoui S Droz JP Flechon A Errihani H

Deacutepartement doncologie meacutedicale France ismailinabilyahoofrAbstractBladder cancer represents for man the second genitourinary cancer after prostate cancer Urothelial carcinoma is the most predominant histological type In up to 70 of the cases the diagnosis of bladder cancer is performed at early stages (Ta-T1) In this situation the treatment of the disease is the transurethral resection with or without intravesical treatment (BCG Amiticyne) In advanced disease treatment is essentially palliative with chemotherapy based on cisplatin type MVAC (methotrexate vinblastine doxorubicin and cisplatin) or gemcitabine-cisplatin In invasive stages (T2-T3-T4) the radical cystoprostatectomy combined with urinary diversion for man and the pelvectomy for woman are the gold standard However over 50 of these patients experienced metastatic recurrence during their evolution which prompted investigators last 10 years to assess the value of neacuteoadjuvant chemotherapy in their management Indeed neoadjuvant chemotherapy is now recognized as a standard by numerous American and European institutions However adjuvant chemotherapy remains controversial even for patients with lymph node involvement The purpose of this literature review is to highlight the role of chemotherapy in the management of urothelial carcinoma of bladder with locally advanced and metastatic disease The role of targeted therapies alone in combination with chemotherapy and in maintenance is being evaluated

wwwthelancetcom Vol 376 September 25 2010

Metotrexato nellrsquoartrite reumatoide

Analoghi delle Purine

Appartengono a questa categoria

1) Azatioprina egrave la principale di questa classe Ersquo largamente utilizzata come immunosoppressivo nei trapianti drsquoorgano prevenendo la moltiplicazione linfocitaria nella fase di induzione del sistema immunitario Interferisce sia attraverso lrsquoinibizione della risposta immunitaria mediata dai linfociti che da quella umurale Ersquo metabolizzata in 6-mercaptopurinea che agisce come analogo delle purine ed inibitore della sintesi del DNA Ersquo usata in caso di autoimmunitagrave 2) Mercaptopurina 3) Tioguanina egrave usata nelle leucemie acute4) Fludarabina inibisce la DNA polimerasi la DNA primasi e ligasi I ed egrave fase specifica

Oncotarget 2010 Nov1(7)472-82Refractory chronic lymphocytic leukemia--new therapeutic strategiesSchnaiter A Stilgenbauer SUniversity of Ulm Ulm GermanyAbstractTreatment outcome of chronic lymphocytic leukemia (CLL) has considerably improved since the introduction of fludarabine (F) as part of the standard therapy Nevertheless refractoriness to fludarabine occurs in a significant number of patients and is associated with an unfavorable prognosis Important risk factors are 17p deletion andor mutation of TP53 For this subgroup the CD52 antibody alemtuzumab (A) presents a new treatment approach and has already been approved Meanwhile we have to face also refractoriness to alemtuzumab Importantly the monoclonal CD20 antibody ofatumumab has now shown efficacy in F and A double-refractory CLL The next generation CD20 antibody GA-101 is currently compared to rituximab (R) and will possibly be its more potent successor Further B-cell antigens are targeted by lumiliximab (CD23) TRU-016 (CD37) and blinatumomab (CD19) Apart from monoclonal antibody therapies a great number of small molecules are examined for the treatment of refractory and relapsed CLL Most of these agents aim to overcome apoptosis resistance in CLL cells or influence the microenvironment Typical targets are regulators of the cell cycle and antiapoptotic molecules like the members of the Bcl-2 family Up to now the most promising agents appear to be flavopiridol and lenalidomide among others

Analoghi delle Purine

Appartengono a questa categoria

1) Azatioprina egrave la principale di questa classe Ersquo largamente utilizzata come immunosoppressivo nei trapianti drsquoorgano prevenendo la moltiplicazione linfocitaria nella fase di induzione del sistema immunitario Interferisce sia attraverso lrsquoinibizione della risposta immunitaria mediata dai linfociti che da quella umurale Ersquo metabolizzata in 6-mercaptopurinea che agisce come analogo delle purine ed inibitore della sintesi del DNA Ersquo usata in caso di autoimmunitagrave 2) Mercaptopurina 3) Tioguanina egrave usata nelle leucemie acute4) Fludarabina inibisce la DNA polimerasi la DNA primasi e ligasi I ed egrave fase specifica

Oncotarget 2010 Nov1(7)472-82Refractory chronic lymphocytic leukemia--new therapeutic strategiesSchnaiter A Stilgenbauer SUniversity of Ulm Ulm GermanyAbstractTreatment outcome of chronic lymphocytic leukemia (CLL) has considerably improved since the introduction of fludarabine (F) as part of the standard therapy Nevertheless refractoriness to fludarabine occurs in a significant number of patients and is associated with an unfavorable prognosis Important risk factors are 17p deletion andor mutation of TP53 For this subgroup the CD52 antibody alemtuzumab (A) presents a new treatment approach and has already been approved Meanwhile we have to face also refractoriness to alemtuzumab Importantly the monoclonal CD20 antibody ofatumumab has now shown efficacy in F and A double-refractory CLL The next generation CD20 antibody GA-101 is currently compared to rituximab (R) and will possibly be its more potent successor Further B-cell antigens are targeted by lumiliximab (CD23) TRU-016 (CD37) and blinatumomab (CD19) Apart from monoclonal antibody therapies a great number of small molecules are examined for the treatment of refractory and relapsed CLL Most of these agents aim to overcome apoptosis resistance in CLL cells or influence the microenvironment Typical targets are regulators of the cell cycle and antiapoptotic molecules like the members of the Bcl-2 family Up to now the most promising agents appear to be flavopiridol and lenalidomide among others

Oncotarget 2010 Nov1(7)472-82Refractory chronic lymphocytic leukemia--new therapeutic strategiesSchnaiter A Stilgenbauer SUniversity of Ulm Ulm GermanyAbstractTreatment outcome of chronic lymphocytic leukemia (CLL) has considerably improved since the introduction of fludarabine (F) as part of the standard therapy Nevertheless refractoriness to fludarabine occurs in a significant number of patients and is associated with an unfavorable prognosis Important risk factors are 17p deletion andor mutation of TP53 For this subgroup the CD52 antibody alemtuzumab (A) presents a new treatment approach and has already been approved Meanwhile we have to face also refractoriness to alemtuzumab Importantly the monoclonal CD20 antibody ofatumumab has now shown efficacy in F and A double-refractory CLL The next generation CD20 antibody GA-101 is currently compared to rituximab (R) and will possibly be its more potent successor Further B-cell antigens are targeted by lumiliximab (CD23) TRU-016 (CD37) and blinatumomab (CD19) Apart from monoclonal antibody therapies a great number of small molecules are examined for the treatment of refractory and relapsed CLL Most of these agents aim to overcome apoptosis resistance in CLL cells or influence the microenvironment Typical targets are regulators of the cell cycle and antiapoptotic molecules like the members of the Bcl-2 family Up to now the most promising agents appear to be flavopiridol and lenalidomide among others

Analoghi delle Pirimidine

Appartengono a questa categoria

1) 5-fluorouracil inibisce la timidilato sintetasi inibendo la metilazione dellrsquoacido desossiuridilico ad acido timidilico e quindi interferendo con la sintesi di DNA

2) Floxuridine

3) Cytosine arabinoside

BJU Int 2011 Jul108(2)168-79 doi 101111j1464-410X201110341x

Gemcitabine chemotherapy for the treatment of metastatic bladder carcinomaShelley MD Cleves A Wilt TJ Mason MD

Cochrane Urological Cancers Unit Velindre NHS Trust Cardiff Cardiff UK mikeshelleywalesnhsukAbstractOBJECTIVEbull To systematically review the literature on gemcitabine chemotherapy for advanced or metastatic bladder cancerMATERIALS AND METHODSbull The Medical Literature Analysis and Retrieval System Onlinedatabase (MEDLINE) the Excerpta Medicadatabase (EMBASE) the Cumulative Index to Nursing and Allied Health Literature database(CIHNAL) the Cochrane database of randomized trials the Literatura Latino-Americana e do Caribe emCiecircncias da Sauacutededatabase (LILACS) and Web of Science were searched to identify trials of gemcitabine for metastatic bladder cancer Also searched were international guidelines on metastatic prostate cancer trial registries and recent systematic reviews Data on trial design survival tumour response and toxicity outcomes were extracted from relevant studiesRESULTSbull This review identified six randomized trials of combined chemotherapy with gemcitabine for the management of unresectable locally advanced or metastatic bladder cancer bull One trial compared gemcitabine plus cisplatin (GCis) with methotrexatevinblastinedoxorubicincisplatin(MVAC) and found no difference in overall survival (OS hazard ratio 109) but a better safety profile with GCis which was suggested as the treatment of choice bull A second trial evaluated GCis againstgemcitabine plus carboplatin (GCarbo) and reported similar median OS (128 vs 98 months) disease progression (83 vs 73 months) and tumour response rates (66 vs 56) for the two patient groups bull A third trial compared GCis with GCis plus paclitaxel (GCisPac) and showed no significant difference in median OS (123 vs 153 months) and response rates (44 vs 43) but greater toxicity with GCisPac bull A fourth trial assessed GCarbo against methotrexate plus carboplatin plus vinblastine in patients unfit for cisplatin-based chemotherapy and found similar tumour response rates for each regime (38 vs 20) but the triplet regime was more toxic bull Two other randomized studies compared a 2-weekly maintenance regime of gemcitabine plus paclitaxel with a 3-weelky regime given for a maximum of six cycles and found that the maintenance schedule did not confer any additional survival benefit bull In all 53 observational studies of gemcitabine chemotherapy were identified that varied considerably in the drug combinations used and schedules Overall response rates (17-78) and median OS (64-240 months) were variable with no combination being clearly superiorCONCLUSIONS

bull Gemcitabine combined chemotherapy is active in the management of metastatic bladder cancer bull GCis may be considered an alternative regime to MVAC bull GCarbo should be considered for patients unfit for cisplatin-based therapy

ANTIMITOTICI

A questa categoria appartengono

1) Tassani

2) Alcaloidi della Vinca

Sito di azione degli antimitotici

Paclitaxel Vincristine

Il Paclitaxel egrave un inibitore della mitosi cellulare usato in chemioterapia Ersquo

stato scoperto nel 1967 quando venne isolato da un albero secolare del

pacifico il Taxus brevifolia ed egrave stato sviluppato commercialmente dalla

Bristol-Myers Squibb (BMS) con il nome di paclitaxel

Il paclitaxel interferisce con la normale rottura dei microtubuli

stabilizzando queste strutture Viene distrutta perciograve la capacitagrave cellulare

di usare il citoscheletro in maniera flessibile legandosi alla subunitagrave beta

della tubulina che costituisce lrsquounitagrave funzionale dei microtubuli

stabilizzando lrsquointera struttura

Meccanismo di Azione

Il Paclitaxel egrave un inibitore della mitosi cellulare usato in chemioterapia Ersquo

stato scoperto nel 1967 quando venne isolato da un albero secolare del

pacifico il Taxus brevifolia ed egrave stato sviluppato commercialmente dalla

Bristol-Myers Squibb (BMS) con il nome di paclitaxel

Il paclitaxel interferisce con la normale rottura dei microtubuli

stabilizzando queste strutture Viene distrutta perciograve la capacitagrave cellulare

di usare il citoscheletro in maniera flessibile legandosi alla subunitagrave beta

della tubulina che costituisce lrsquounitagrave funzionale dei microtubuli

stabilizzando lrsquointera struttura

Meccanismo di Azione

microtuboli

Il Paclitaxel egrave utilizzato per trattare pazienti con

Cancro al polmoneCancro alle ovaieCancro della mammellaSarcoma di Kaposi

Il sarcoma di caposi egrave caratterizzato da una crescita anormale dei vasi sanguigni che producono lesioni cutanee che possono avvenire anche internamente

Il Paclitaxel egrave usato anche nel prevenire la ristenosi

Lancet 2009 Oct 17374(9698)1371-82 Epub 2009 Sep 28Ovarian cancerHennessy BT Coleman RL Markman MDepartment of Gynecologic Medical Oncology University of Texas MD Anderson Cancer Center Houston TX 77030 USAAbstractThe standard initial management of epithelial ovarian cancer consists of surgical staging operative tumour debulking including total abdominal hysterectomy and bilateral salpingo-oophorectomy and administration of six cycles of intravenous chemotherapy with carboplatin and paclitaxel Extensive and largely retrospective experience has shown that optimum surgical debulking to leave residual tumour deposits that are less than 1 cm in size is associated with improved patient outcomes However 75 of patients present with advanced (stage III or IV) disease and although more than 80 of these women benefit from first-line therapy tumour recurrence occurs in almost all these patients at a median of 15 months from diagnosis Second-line treatments can improve survival and quality of life but are not curative Advances in screening and understanding of molecular pathogenesis of ovarian cancer and development of novel targeted therapies (eg bevacizumab) and practical intraperitoneal techniques for drug delivery are most likely to improve patient outcomes

Il Paclitaxel egrave utilizzato per trattare pazienti con

Cancro al polmoneCancro alle ovaieCancro della mammellaSarcoma di Kaposi

Il sarcoma di caposi egrave caratterizzato da una crescita anormale dei vasi sanguigni che producono lesioni cutanee che possono avvenire anche internamente

Il Paclitaxel egrave usato anche nel prevenire la ristenosi

Lancet 2009 Oct 17374(9698)1371-82 Epub 2009 Sep 28Ovarian cancerHennessy BT Coleman RL Markman MDepartment of Gynecologic Medical Oncology University of Texas MD Anderson Cancer Center Houston TX 77030 USAAbstractThe standard initial management of epithelial ovarian cancer consists of surgical staging operative tumour debulking including total abdominal hysterectomy and bilateral salpingo-oophorectomy and administration of six cycles of intravenous chemotherapy with carboplatin and paclitaxel Extensive and largely retrospective experience has shown that optimum surgical debulking to leave residual tumour deposits that are less than 1 cm in size is associated with improved patient outcomes However 75 of patients present with advanced (stage III or IV) disease and although more than 80 of these women benefit from first-line therapy tumour recurrence occurs in almost all these patients at a median of 15 months from diagnosis Second-line treatments can improve survival and quality of life but are not curative Advances in screening and understanding of molecular pathogenesis of ovarian cancer and development of novel targeted therapies (eg bevacizumab) and practical intraperitoneal techniques for drug delivery are most likely to improve patient outcomes

Lancet 2009 Oct 17374(9698)1371-82 Epub 2009 Sep 28Ovarian cancerHennessy BT Coleman RL Markman MDepartment of Gynecologic Medical Oncology University of Texas MD Anderson Cancer Center Houston TX 77030 USAAbstractThe standard initial management of epithelial ovarian cancer consists of surgical staging operative tumour debulking including total abdominal hysterectomy and bilateral salpingo-oophorectomy and administration of six cycles of intravenous chemotherapy with carboplatin and paclitaxel Extensive and largely retrospective experience has shown that optimum surgical debulking to leave residual tumour deposits that are less than 1 cm in size is associated with improved patient outcomes However 75 of patients present with advanced (stage III or IV) disease and although more than 80 of these women benefit from first-line therapy tumour recurrence occurs in almost all these patients at a median of 15 months from diagnosis Second-line treatments can improve survival and quality of life but are not curative Advances in screening and understanding of molecular pathogenesis of ovarian cancer and development of novel targeted therapies (eg bevacizumab) and practical intraperitoneal techniques for drug delivery are most likely to improve patient outcomes

Effetti collaterali

I piugrave comuni effetti collaterali sono nausea e vomito perdita dellrsquoappetito cambiamento del gusto dolore delle articolazioni che dura diversi giorni formicolio

alle estremitagraveEffetti collaterali piugrave gravi sono sanguinamento nel sito di iniezione febbre tosse respiro affannato

ALCALOIDI DI ORIGINE VEGETALE

Meccanismo di AzioneLa tubulina egrave una proteina strutturale che polimerizza formando i microtubuli Il citoscheletro egrave costituito da

microtubuli La vincristina lega i dimeri di tubulina inibendo lrsquoassemblaggio strutturale di questi arrestando la

mitosi in metafase Gli alcaloidi della vinca perciograve agiscono rapidamente in cellule che si dividono quali

quelle cancerose ma anche in quelle dellrsquoepitelio intestinale e midollari

Gli alcaloidi della vinca sono Vincristina Vinblastina

La vincristina egrave un alcaloide della Catharanthus roseus originariamente chiamata Vinca rosea Ersquo un inibitore della mitosi cellulare ed egrave usata nella chemioterapia

CA Cancer J Clin 2010 Nov-Dec60(6)393-408 Epub 2010 Oct 28

Improving outcomes for patients with diffuse large B-cell lymphomaFlowers CR Sinha R Vose JM

Bone Marrow and Stem Cell Transplantation Department of Hematology and Oncology Winship Cancer Institute Emory University School of Medicine Atlanta GA 30322 USA BarbaraCopelandemoryhealthcareorgAbstractDiffuse large B-cell lymphoma (DLBCL) is the most commonly occurring form of non-Hodgkin lymphoma in the western world Until the mid 1990s the incidence of DLBCL increased in both sexes across racial categories and across all age groups except the very young the etiology of most cases remains unknown DLBCL is associated with an aggressive natural history but it can be cured with combination chemotherapy regimens like cyclophosphamide doxorubicin vincristine and prednisone (CHOP) which has been the mainstay of therapy for several decades Remarkable progress has been made in understanding the biological heterogeneity of DLBCL and in improving survival for DLBCL patients with novel combinations of chemotherapy and immunotherapy Gene expression profiling (GEP) has uncovered DLBCL subtypes that have distinct clinical behaviors and prognoses and the addition of the monoclonal antibody rituximab to CHOP has markedly improved outcomes Future approaches to DLBCL management will use molecular signatures identified through GEP to provide prognostic information and to isolate therapeutic targets that are being evaluated for DLBCL patients who relapse or those with high risk disease

ALCALOIDI DI ORIGINE VEGETALE

Meccanismo di AzioneLa tubulina egrave una proteina strutturale che polimerizza formando i microtubuli Il citoscheletro egrave costituito da

microtubuli La vincristina lega i dimeri di tubulina inibendo lrsquoassemblaggio strutturale di questi arrestando la

mitosi in metafase Gli alcaloidi della vinca perciograve agiscono rapidamente in cellule che si dividono quali

quelle cancerose ma anche in quelle dellrsquoepitelio intestinale e midollari

Gli alcaloidi della vinca sono Vincristina Vinblastina

La vincristina egrave un alcaloide della Catharanthus roseus originariamente chiamata Vinca rosea Ersquo un inibitore della mitosi cellulare ed egrave usata nella chemioterapia

CA Cancer J Clin 2010 Nov-Dec60(6)393-408 Epub 2010 Oct 28

Improving outcomes for patients with diffuse large B-cell lymphomaFlowers CR Sinha R Vose JM

Bone Marrow and Stem Cell Transplantation Department of Hematology and Oncology Winship Cancer Institute Emory University School of Medicine Atlanta GA 30322 USA BarbaraCopelandemoryhealthcareorgAbstractDiffuse large B-cell lymphoma (DLBCL) is the most commonly occurring form of non-Hodgkin lymphoma in the western world Until the mid 1990s the incidence of DLBCL increased in both sexes across racial categories and across all age groups except the very young the etiology of most cases remains unknown DLBCL is associated with an aggressive natural history but it can be cured with combination chemotherapy regimens like cyclophosphamide doxorubicin vincristine and prednisone (CHOP) which has been the mainstay of therapy for several decades Remarkable progress has been made in understanding the biological heterogeneity of DLBCL and in improving survival for DLBCL patients with novel combinations of chemotherapy and immunotherapy Gene expression profiling (GEP) has uncovered DLBCL subtypes that have distinct clinical behaviors and prognoses and the addition of the monoclonal antibody rituximab to CHOP has markedly improved outcomes Future approaches to DLBCL management will use molecular signatures identified through GEP to provide prognostic information and to isolate therapeutic targets that are being evaluated for DLBCL patients who relapse or those with high risk disease

CA Cancer J Clin 2010 Nov-Dec60(6)393-408 Epub 2010 Oct 28

Improving outcomes for patients with diffuse large B-cell lymphomaFlowers CR Sinha R Vose JM

Bone Marrow and Stem Cell Transplantation Department of Hematology and Oncology Winship Cancer Institute Emory University School of Medicine Atlanta GA 30322 USA BarbaraCopelandemoryhealthcareorgAbstractDiffuse large B-cell lymphoma (DLBCL) is the most commonly occurring form of non-Hodgkin lymphoma in the western world Until the mid 1990s the incidence of DLBCL increased in both sexes across racial categories and across all age groups except the very young the etiology of most cases remains unknown DLBCL is associated with an aggressive natural history but it can be cured with combination chemotherapy regimens like cyclophosphamide doxorubicin vincristine and prednisone (CHOP) which has been the mainstay of therapy for several decades Remarkable progress has been made in understanding the biological heterogeneity of DLBCL and in improving survival for DLBCL patients with novel combinations of chemotherapy and immunotherapy Gene expression profiling (GEP) has uncovered DLBCL subtypes that have distinct clinical behaviors and prognoses and the addition of the monoclonal antibody rituximab to CHOP has markedly improved outcomes Future approaches to DLBCL management will use molecular signatures identified through GEP to provide prognostic information and to isolate therapeutic targets that are being evaluated for DLBCL patients who relapse or those with high risk disease

ANTIBIOTICI ANTITUMORALI

Tra gli antibiotici antitumorali sono di tre classi

1) Antracicline (Doxorubicina)

2) Antracenedioni (Mitoxantrone)

3) Streptomicine (Actinomicina Bleomicina Mitomicina)

Meccanismo di Azione

Lrsquoesatto meccanismo dellrsquo azione antitumorale della doxorubicina egrave complesso e ancora non ben conosciuto Comunque si pensa che possa intercalarsi nel DNA inibendo la topoisomerasi II la quale apre il DNA per la trascrizione

Uso clinico

La doxorubicina egrave comunemente usata per trattare la leucemia il linfoma di Hodgkin cancro alla vescica alla

mammella allo stomaco ai polmoni alle ovaie alla tiroide nel sarcoma di tessuti molli etc

I regimi classici con la doxorubicina sono

1)Doxorubicina + ciclofosfamide + adriamicina

2)Adriamicina + bleomicina + vinblastina + dacarbazide

3)5-fluorouracile + adriamicina + ciclofosfamide

Expert Rev Anticancer Ther 2008 Dec8(12)1859-69

Efficacy and toxicity of nonpegylated liposomal doxorubicin in breast cancerStavridi F Palmieri C

Department of Medical Oncology St Georges Hospital Blackshaw Road London SW18 0QT UKAbstract

Anthracyclines including doxorubicin are the mainstay of therapy for breast cancer However doxorubicin can cause dose-dependent cardiotoxicity limiting the cumulative dose Liposomal conjugation of doxorubicin results in preferential distribution of doxorubicin in the tumor compared with normal tissues Nonpegylated liposomal doxorubicin (NPLD) has demonstrated reduced cardiac toxicity with anti-tumor responses comparable to those of conventional doxorubicin The substitution of NPLD for conventional anthracyclines significantly reduces the cumulative cardiotoxicity while allowing a higher cumulative dose This allows patients who have already received the maximum cumulative dose of doxorubicin to receive further doxorubicin as well as those with risk factors for anthracycline-induced cardiotoxicity The favorable cardiac safety profile of NPLD may allow it to be combined with newer therapies such as trastuzumab

Uso clinico

La doxorubicina egrave comunemente usata per trattare la leucemia il linfoma di Hodgkin cancro alla vescica alla

mammella allo stomaco ai polmoni alle ovaie alla tiroide nel sarcoma di tessuti molli etc

I regimi classici con la doxorubicina sono

1)Doxorubicina + ciclofosfamide + adriamicina

2)Adriamicina + bleomicina + vinblastina + dacarbazide

3)5-fluorouracile + adriamicina + ciclofosfamide

Expert Rev Anticancer Ther 2008 Dec8(12)1859-69

Efficacy and toxicity of nonpegylated liposomal doxorubicin in breast cancerStavridi F Palmieri C

Department of Medical Oncology St Georges Hospital Blackshaw Road London SW18 0QT UKAbstract

Anthracyclines including doxorubicin are the mainstay of therapy for breast cancer However doxorubicin can cause dose-dependent cardiotoxicity limiting the cumulative dose Liposomal conjugation of doxorubicin results in preferential distribution of doxorubicin in the tumor compared with normal tissues Nonpegylated liposomal doxorubicin (NPLD) has demonstrated reduced cardiac toxicity with anti-tumor responses comparable to those of conventional doxorubicin The substitution of NPLD for conventional anthracyclines significantly reduces the cumulative cardiotoxicity while allowing a higher cumulative dose This allows patients who have already received the maximum cumulative dose of doxorubicin to receive further doxorubicin as well as those with risk factors for anthracycline-induced cardiotoxicity The favorable cardiac safety profile of NPLD may allow it to be combined with newer therapies such as trastuzumab

Expert Rev Anticancer Ther 2008 Dec8(12)1859-69

Efficacy and toxicity of nonpegylated liposomal doxorubicin in breast cancerStavridi F Palmieri C

Department of Medical Oncology St Georges Hospital Blackshaw Road London SW18 0QT UKAbstract

Anthracyclines including doxorubicin are the mainstay of therapy for breast cancer However doxorubicin can cause dose-dependent cardiotoxicity limiting the cumulative dose Liposomal conjugation of doxorubicin results in preferential distribution of doxorubicin in the tumor compared with normal tissues Nonpegylated liposomal doxorubicin (NPLD) has demonstrated reduced cardiac toxicity with anti-tumor responses comparable to those of conventional doxorubicin The substitution of NPLD for conventional anthracyclines significantly reduces the cumulative cardiotoxicity while allowing a higher cumulative dose This allows patients who have already received the maximum cumulative dose of doxorubicin to receive further doxorubicin as well as those with risk factors for anthracycline-induced cardiotoxicity The favorable cardiac safety profile of NPLD may allow it to be combined with newer therapies such as trastuzumab

INIBITORI DELLE TOPOISOMERASI

Gli inibitori delle topoisomerasi sono

1) Camptotecine (Topotecano e irinotecano)

2) Podofillotossine (Etoposide

La camptotecina egrave un alcaloide citotossico il quale inibisce la topoisomerasi I Ersquo stata scoperta nel 1966 dalla corteccia di un albero la Camptotheca acuminata nativo della Cina Ha una bassa solubilitagrave percui i chimici farmaceutici hanno prodotto due nuove molecole analoghe della camptotecina e piugrave solubili quali il topotecano e lrsquoirinotecano

A) La Topoisomerases I si lega alla doppia elica del DNA e si lega in modo covalente al terminale 3rsquo della rottura della catena Tutte le altre topoisomerasi si legano alla porzione 5rsquo della catena rotta del DNA Questi complessi sono stabilizzati selettivamente dalla camptotecina

B) Sito catalitico della topoisomerasi I Residuo catalitico della tirosina porta lrsquoattacco nucleofilico e rottura del legame estere fosforico presente nel DNA

ANTICORPI MONOCLONALI

Sono una classe di farmaci in grande sviluppo nella terapia antitumorale Sono molto specifici in quanto di legano ad anticorpi presenti sulle membrane cellulari di cellule tumorali

Il trastuzumab egrave un anticorpo monoclonale umanizzato che agisce al recettore Her 2 Questo tipo di recettore egrave altamente espresso nel tumore della mammella Ersquo somministrato una volta alla settimana o ogni tre settimane per infusione endovenosa per 30-90 minuti

Alemtuzumab It is used to treat patients with chronic lymphocytic leukaemia (CLL) a cancer of the lymphocytes

1) Murine (muro-ab) (100 di origine di topo)Es Muromonab

2) Chimeric (-ximab) (33 di origine di topo)Es Rituximab

3) Humanized (-xumab -zumab) (5-10 di origine di topo)EsAlemtuzumab

4) Human (-mumab) (0 di origine di topo)EsAdalimumab

Nomenclatura degli anticorpi monoclonali in terapia

Struttura di un anticorpo

Struttura degli anticorpi

La famiglia delle immunoglobuline

The first type of antibody classification is Immunoglobulin A (IgA) which protects mucosal surfaces with a fluid like secretion (Vedhara amp Irwin 2005) IgA is found in serum mucus saliva tears sweat and milk and has also been associated with being transferred to an unborn child (passive immunity) and can also protect the child after birth for several months This time frame can be further increased when the mother breast-feeds ( Niers Stasse-Wolthuis Rombouts amp Rijkers 2007) A second type of antibody classification is Immunoglobulin E (IgE) which triggers the release of histamines by attaching to antigens basophils and mast cells ( Vedhara amp Irwin 2005) IgE does not make up a very large portion of antigens but it is responsible for reactions resulting in hives asthma and hayfever as examples (Paustian amp Roberts 2005) A third type of antibody classification is Immunoglobulin M (IgM) which forms antibody-antigens processed by the liver and stimulates complement-mediated lysis (Vedhara amp Irwin 2005) IgM makes up about 10 of the total antibodies and it is very important in the initial phases of an illness to stop the spreading of the pathogen ( Paustian amp Roberts 2005) A fourth type of antibody classification is Immunoglobulin G (IgG) which allows for the consumption of pathogens such as bacteria by coating them so that macrophages and neutrophils will be able to recognize them as pathogens (Vedhara amp Irwin 2005) IgG is the largest classification of circulating antibodies ( Paustian amp Roberts 2005) The fifth type of antibody classification is Immunoglobulin D (IgD) which is lacking in enough research to clearly understand its functions (Vedhara amp Irwin 2005) This antibody located on the surface of B-lymphocytes (Paustian amp Roberts 2005) Currently there are research studies being conducted on immature IgD antibodies to transfer them to becoming mature B cells in an effort to try and gain further understanding of the actual function IgD antibodies (Koelsch et al 2007)

Cellule contenenti una forte sovraespressione di HER-2neu mostrano una migliore inibizione della crescita per effetto dei trattamenti chemioterapici rispetto a quella ottenuta nei sistemi cellulari con piugrave basso livello di espressione

Herneu

LrsquoHER2neu (conosciuto anche come ErbB-2) sta ad indicare Human Epidermal growth factor Receptor 2 ed egrave una proteina ad alta aggressivitagrave nel cancro della mammella Ersquo un membro della famiglia proteica degli ErbB conosciuta piugrave come epidermal growth factor receptor family HER2neu egrave anche conosciuta come CD340 (cluster of differentiation 340) e p185 Ersquo codificata nel gene ERBB2

ANTICORPI MONOCLONALI

Sono una classe di farmaci in grande sviluppo nella terapia antitumorale Sono molto specifici in quanto di legano ad anticorpi presenti sulle membrane cellulari di cellule tumorali

Il trastuzumab egrave un anticorpo monoclonale umanizzato che agisce al recettore Her 2 Questo tipo di recettore egrave altamente espresso nel tumore della mammella Ersquo somministrato una volta alla settimana o ogni tre settimane per infusione endovenosa per 30-90 minuti

Alemtuzumab It is used to treat patients with chronic lymphocytic leukaemia (CLL) a cancer of the lymphocytes

1) Murine (muro-ab) (100 di origine di topo)Es Muromonab

2) Chimeric (-ximab) (33 di origine di topo)Es Rituximab

3) Humanized (-xumab -zumab) (5-10 di origine di topo)EsAlemtuzumab

4) Human (-mumab) (0 di origine di topo)EsAdalimumab

Nomenclatura degli anticorpi monoclonali in terapia

Struttura di un anticorpo

Struttura degli anticorpi

La famiglia delle immunoglobuline

The first type of antibody classification is Immunoglobulin A (IgA) which protects mucosal surfaces with a fluid like secretion (Vedhara amp Irwin 2005) IgA is found in serum mucus saliva tears sweat and milk and has also been associated with being transferred to an unborn child (passive immunity) and can also protect the child after birth for several months This time frame can be further increased when the mother breast-feeds ( Niers Stasse-Wolthuis Rombouts amp Rijkers 2007) A second type of antibody classification is Immunoglobulin E (IgE) which triggers the release of histamines by attaching to antigens basophils and mast cells ( Vedhara amp Irwin 2005) IgE does not make up a very large portion of antigens but it is responsible for reactions resulting in hives asthma and hayfever as examples (Paustian amp Roberts 2005) A third type of antibody classification is Immunoglobulin M (IgM) which forms antibody-antigens processed by the liver and stimulates complement-mediated lysis (Vedhara amp Irwin 2005) IgM makes up about 10 of the total antibodies and it is very important in the initial phases of an illness to stop the spreading of the pathogen ( Paustian amp Roberts 2005) A fourth type of antibody classification is Immunoglobulin G (IgG) which allows for the consumption of pathogens such as bacteria by coating them so that macrophages and neutrophils will be able to recognize them as pathogens (Vedhara amp Irwin 2005) IgG is the largest classification of circulating antibodies ( Paustian amp Roberts 2005) The fifth type of antibody classification is Immunoglobulin D (IgD) which is lacking in enough research to clearly understand its functions (Vedhara amp Irwin 2005) This antibody located on the surface of B-lymphocytes (Paustian amp Roberts 2005) Currently there are research studies being conducted on immature IgD antibodies to transfer them to becoming mature B cells in an effort to try and gain further understanding of the actual function IgD antibodies (Koelsch et al 2007)

Cellule contenenti una forte sovraespressione di HER-2neu mostrano una migliore inibizione della crescita per effetto dei trattamenti chemioterapici rispetto a quella ottenuta nei sistemi cellulari con piugrave basso livello di espressione

Herneu

LrsquoHER2neu (conosciuto anche come ErbB-2) sta ad indicare Human Epidermal growth factor Receptor 2 ed egrave una proteina ad alta aggressivitagrave nel cancro della mammella Ersquo un membro della famiglia proteica degli ErbB conosciuta piugrave come epidermal growth factor receptor family HER2neu egrave anche conosciuta come CD340 (cluster of differentiation 340) e p185 Ersquo codificata nel gene ERBB2

1) Murine (muro-ab) (100 di origine di topo)Es Muromonab

2) Chimeric (-ximab) (33 di origine di topo)Es Rituximab

3) Humanized (-xumab -zumab) (5-10 di origine di topo)EsAlemtuzumab

4) Human (-mumab) (0 di origine di topo)EsAdalimumab

Nomenclatura degli anticorpi monoclonali in terapia

Struttura di un anticorpo

Struttura degli anticorpi

La famiglia delle immunoglobuline

The first type of antibody classification is Immunoglobulin A (IgA) which protects mucosal surfaces with a fluid like secretion (Vedhara amp Irwin 2005) IgA is found in serum mucus saliva tears sweat and milk and has also been associated with being transferred to an unborn child (passive immunity) and can also protect the child after birth for several months This time frame can be further increased when the mother breast-feeds ( Niers Stasse-Wolthuis Rombouts amp Rijkers 2007) A second type of antibody classification is Immunoglobulin E (IgE) which triggers the release of histamines by attaching to antigens basophils and mast cells ( Vedhara amp Irwin 2005) IgE does not make up a very large portion of antigens but it is responsible for reactions resulting in hives asthma and hayfever as examples (Paustian amp Roberts 2005) A third type of antibody classification is Immunoglobulin M (IgM) which forms antibody-antigens processed by the liver and stimulates complement-mediated lysis (Vedhara amp Irwin 2005) IgM makes up about 10 of the total antibodies and it is very important in the initial phases of an illness to stop the spreading of the pathogen ( Paustian amp Roberts 2005) A fourth type of antibody classification is Immunoglobulin G (IgG) which allows for the consumption of pathogens such as bacteria by coating them so that macrophages and neutrophils will be able to recognize them as pathogens (Vedhara amp Irwin 2005) IgG is the largest classification of circulating antibodies ( Paustian amp Roberts 2005) The fifth type of antibody classification is Immunoglobulin D (IgD) which is lacking in enough research to clearly understand its functions (Vedhara amp Irwin 2005) This antibody located on the surface of B-lymphocytes (Paustian amp Roberts 2005) Currently there are research studies being conducted on immature IgD antibodies to transfer them to becoming mature B cells in an effort to try and gain further understanding of the actual function IgD antibodies (Koelsch et al 2007)

Cellule contenenti una forte sovraespressione di HER-2neu mostrano una migliore inibizione della crescita per effetto dei trattamenti chemioterapici rispetto a quella ottenuta nei sistemi cellulari con piugrave basso livello di espressione

Herneu

LrsquoHER2neu (conosciuto anche come ErbB-2) sta ad indicare Human Epidermal growth factor Receptor 2 ed egrave una proteina ad alta aggressivitagrave nel cancro della mammella Ersquo un membro della famiglia proteica degli ErbB conosciuta piugrave come epidermal growth factor receptor family HER2neu egrave anche conosciuta come CD340 (cluster of differentiation 340) e p185 Ersquo codificata nel gene ERBB2

Struttura di un anticorpo

Struttura degli anticorpi

La famiglia delle immunoglobuline

The first type of antibody classification is Immunoglobulin A (IgA) which protects mucosal surfaces with a fluid like secretion (Vedhara amp Irwin 2005) IgA is found in serum mucus saliva tears sweat and milk and has also been associated with being transferred to an unborn child (passive immunity) and can also protect the child after birth for several months This time frame can be further increased when the mother breast-feeds ( Niers Stasse-Wolthuis Rombouts amp Rijkers 2007) A second type of antibody classification is Immunoglobulin E (IgE) which triggers the release of histamines by attaching to antigens basophils and mast cells ( Vedhara amp Irwin 2005) IgE does not make up a very large portion of antigens but it is responsible for reactions resulting in hives asthma and hayfever as examples (Paustian amp Roberts 2005) A third type of antibody classification is Immunoglobulin M (IgM) which forms antibody-antigens processed by the liver and stimulates complement-mediated lysis (Vedhara amp Irwin 2005) IgM makes up about 10 of the total antibodies and it is very important in the initial phases of an illness to stop the spreading of the pathogen ( Paustian amp Roberts 2005) A fourth type of antibody classification is Immunoglobulin G (IgG) which allows for the consumption of pathogens such as bacteria by coating them so that macrophages and neutrophils will be able to recognize them as pathogens (Vedhara amp Irwin 2005) IgG is the largest classification of circulating antibodies ( Paustian amp Roberts 2005) The fifth type of antibody classification is Immunoglobulin D (IgD) which is lacking in enough research to clearly understand its functions (Vedhara amp Irwin 2005) This antibody located on the surface of B-lymphocytes (Paustian amp Roberts 2005) Currently there are research studies being conducted on immature IgD antibodies to transfer them to becoming mature B cells in an effort to try and gain further understanding of the actual function IgD antibodies (Koelsch et al 2007)

Cellule contenenti una forte sovraespressione di HER-2neu mostrano una migliore inibizione della crescita per effetto dei trattamenti chemioterapici rispetto a quella ottenuta nei sistemi cellulari con piugrave basso livello di espressione

Herneu

LrsquoHER2neu (conosciuto anche come ErbB-2) sta ad indicare Human Epidermal growth factor Receptor 2 ed egrave una proteina ad alta aggressivitagrave nel cancro della mammella Ersquo un membro della famiglia proteica degli ErbB conosciuta piugrave come epidermal growth factor receptor family HER2neu egrave anche conosciuta come CD340 (cluster of differentiation 340) e p185 Ersquo codificata nel gene ERBB2

Struttura degli anticorpi

La famiglia delle immunoglobuline

The first type of antibody classification is Immunoglobulin A (IgA) which protects mucosal surfaces with a fluid like secretion (Vedhara amp Irwin 2005) IgA is found in serum mucus saliva tears sweat and milk and has also been associated with being transferred to an unborn child (passive immunity) and can also protect the child after birth for several months This time frame can be further increased when the mother breast-feeds ( Niers Stasse-Wolthuis Rombouts amp Rijkers 2007) A second type of antibody classification is Immunoglobulin E (IgE) which triggers the release of histamines by attaching to antigens basophils and mast cells ( Vedhara amp Irwin 2005) IgE does not make up a very large portion of antigens but it is responsible for reactions resulting in hives asthma and hayfever as examples (Paustian amp Roberts 2005) A third type of antibody classification is Immunoglobulin M (IgM) which forms antibody-antigens processed by the liver and stimulates complement-mediated lysis (Vedhara amp Irwin 2005) IgM makes up about 10 of the total antibodies and it is very important in the initial phases of an illness to stop the spreading of the pathogen ( Paustian amp Roberts 2005) A fourth type of antibody classification is Immunoglobulin G (IgG) which allows for the consumption of pathogens such as bacteria by coating them so that macrophages and neutrophils will be able to recognize them as pathogens (Vedhara amp Irwin 2005) IgG is the largest classification of circulating antibodies ( Paustian amp Roberts 2005) The fifth type of antibody classification is Immunoglobulin D (IgD) which is lacking in enough research to clearly understand its functions (Vedhara amp Irwin 2005) This antibody located on the surface of B-lymphocytes (Paustian amp Roberts 2005) Currently there are research studies being conducted on immature IgD antibodies to transfer them to becoming mature B cells in an effort to try and gain further understanding of the actual function IgD antibodies (Koelsch et al 2007)

Cellule contenenti una forte sovraespressione di HER-2neu mostrano una migliore inibizione della crescita per effetto dei trattamenti chemioterapici rispetto a quella ottenuta nei sistemi cellulari con piugrave basso livello di espressione

Herneu

LrsquoHER2neu (conosciuto anche come ErbB-2) sta ad indicare Human Epidermal growth factor Receptor 2 ed egrave una proteina ad alta aggressivitagrave nel cancro della mammella Ersquo un membro della famiglia proteica degli ErbB conosciuta piugrave come epidermal growth factor receptor family HER2neu egrave anche conosciuta come CD340 (cluster of differentiation 340) e p185 Ersquo codificata nel gene ERBB2

La famiglia delle immunoglobuline

The first type of antibody classification is Immunoglobulin A (IgA) which protects mucosal surfaces with a fluid like secretion (Vedhara amp Irwin 2005) IgA is found in serum mucus saliva tears sweat and milk and has also been associated with being transferred to an unborn child (passive immunity) and can also protect the child after birth for several months This time frame can be further increased when the mother breast-feeds ( Niers Stasse-Wolthuis Rombouts amp Rijkers 2007) A second type of antibody classification is Immunoglobulin E (IgE) which triggers the release of histamines by attaching to antigens basophils and mast cells ( Vedhara amp Irwin 2005) IgE does not make up a very large portion of antigens but it is responsible for reactions resulting in hives asthma and hayfever as examples (Paustian amp Roberts 2005) A third type of antibody classification is Immunoglobulin M (IgM) which forms antibody-antigens processed by the liver and stimulates complement-mediated lysis (Vedhara amp Irwin 2005) IgM makes up about 10 of the total antibodies and it is very important in the initial phases of an illness to stop the spreading of the pathogen ( Paustian amp Roberts 2005) A fourth type of antibody classification is Immunoglobulin G (IgG) which allows for the consumption of pathogens such as bacteria by coating them so that macrophages and neutrophils will be able to recognize them as pathogens (Vedhara amp Irwin 2005) IgG is the largest classification of circulating antibodies ( Paustian amp Roberts 2005) The fifth type of antibody classification is Immunoglobulin D (IgD) which is lacking in enough research to clearly understand its functions (Vedhara amp Irwin 2005) This antibody located on the surface of B-lymphocytes (Paustian amp Roberts 2005) Currently there are research studies being conducted on immature IgD antibodies to transfer them to becoming mature B cells in an effort to try and gain further understanding of the actual function IgD antibodies (Koelsch et al 2007)

Cellule contenenti una forte sovraespressione di HER-2neu mostrano una migliore inibizione della crescita per effetto dei trattamenti chemioterapici rispetto a quella ottenuta nei sistemi cellulari con piugrave basso livello di espressione

Herneu

LrsquoHER2neu (conosciuto anche come ErbB-2) sta ad indicare Human Epidermal growth factor Receptor 2 ed egrave una proteina ad alta aggressivitagrave nel cancro della mammella Ersquo un membro della famiglia proteica degli ErbB conosciuta piugrave come epidermal growth factor receptor family HER2neu egrave anche conosciuta come CD340 (cluster of differentiation 340) e p185 Ersquo codificata nel gene ERBB2

The first type of antibody classification is Immunoglobulin A (IgA) which protects mucosal surfaces with a fluid like secretion (Vedhara amp Irwin 2005) IgA is found in serum mucus saliva tears sweat and milk and has also been associated with being transferred to an unborn child (passive immunity) and can also protect the child after birth for several months This time frame can be further increased when the mother breast-feeds ( Niers Stasse-Wolthuis Rombouts amp Rijkers 2007) A second type of antibody classification is Immunoglobulin E (IgE) which triggers the release of histamines by attaching to antigens basophils and mast cells ( Vedhara amp Irwin 2005) IgE does not make up a very large portion of antigens but it is responsible for reactions resulting in hives asthma and hayfever as examples (Paustian amp Roberts 2005) A third type of antibody classification is Immunoglobulin M (IgM) which forms antibody-antigens processed by the liver and stimulates complement-mediated lysis (Vedhara amp Irwin 2005) IgM makes up about 10 of the total antibodies and it is very important in the initial phases of an illness to stop the spreading of the pathogen ( Paustian amp Roberts 2005) A fourth type of antibody classification is Immunoglobulin G (IgG) which allows for the consumption of pathogens such as bacteria by coating them so that macrophages and neutrophils will be able to recognize them as pathogens (Vedhara amp Irwin 2005) IgG is the largest classification of circulating antibodies ( Paustian amp Roberts 2005) The fifth type of antibody classification is Immunoglobulin D (IgD) which is lacking in enough research to clearly understand its functions (Vedhara amp Irwin 2005) This antibody located on the surface of B-lymphocytes (Paustian amp Roberts 2005) Currently there are research studies being conducted on immature IgD antibodies to transfer them to becoming mature B cells in an effort to try and gain further understanding of the actual function IgD antibodies (Koelsch et al 2007)

Cellule contenenti una forte sovraespressione di HER-2neu mostrano una migliore inibizione della crescita per effetto dei trattamenti chemioterapici rispetto a quella ottenuta nei sistemi cellulari con piugrave basso livello di espressione

Herneu

LrsquoHER2neu (conosciuto anche come ErbB-2) sta ad indicare Human Epidermal growth factor Receptor 2 ed egrave una proteina ad alta aggressivitagrave nel cancro della mammella Ersquo un membro della famiglia proteica degli ErbB conosciuta piugrave come epidermal growth factor receptor family HER2neu egrave anche conosciuta come CD340 (cluster of differentiation 340) e p185 Ersquo codificata nel gene ERBB2

Cellule contenenti una forte sovraespressione di HER-2neu mostrano una migliore inibizione della crescita per effetto dei trattamenti chemioterapici rispetto a quella ottenuta nei sistemi cellulari con piugrave basso livello di espressione

Herneu

LrsquoHER2neu (conosciuto anche come ErbB-2) sta ad indicare Human Epidermal growth factor Receptor 2 ed egrave una proteina ad alta aggressivitagrave nel cancro della mammella Ersquo un membro della famiglia proteica degli ErbB conosciuta piugrave come epidermal growth factor receptor family HER2neu egrave anche conosciuta come CD340 (cluster of differentiation 340) e p185 Ersquo codificata nel gene ERBB2

The last decade has witnessed an increasing number ofbiologic markers of breast neoplasms One of the markerswith probable prognostic significance is over-expression of the HER-2neu oncogene within the tumor Although HER-2neu over-expression has been shown to correlate with a poor prognosis in invasive breast cancer little informationis available on the relationship between its over-expressionand the outcome of patients with DCIS Previous studies haveindeed demonstrated that HER-2neu expression correlateswith aggressive histologic features in DCIS but theprognostic significance of HER-2neu expression in the clinicalsetting has yet to be determined

111In-Trastuzumab Fab (111In-humAb4D5-8 Fab) is formed by the conjugation of 111In via the bifunctional chelate diethylenetriamine pentaacetic acid (DTPA) with the Fab fragment of the recombinant humanized monoclonal antibody (MAb) against the antigen of human epidermal growth factor receptor 2 (HER2) 111In-Trastuzumab Fab has been developed for imaging of human breast cancer (1-3)

111In-Trastuzumab Fab (111In-humAb4D5-8 Fab) is formed by the conjugation of 111In via the bifunctional chelate diethylenetriamine pentaacetic acid (DTPA) with the Fab fragment of the recombinant humanized monoclonal antibody (MAb) against the antigen of human epidermal growth factor receptor 2 (HER2) 111In-Trastuzumab Fab has been developed for imaging of human breast cancer (1-3)

Meccanismo di Azione

Lrsquoaumento del numero dei recettore HER2neu (ERB2) avviene nel

20-30 dei casi di tumore alla mammella nei primi stadi della

malattia Questo recettore attiva intracellularmente una via molto

importante che egrave quella della PI3KAkt Questa via egrave associata ai

segnali di mitogenesi coinvolgendo la via della MAPKinasi Nelle

cellule cancerose il recettore HER2neu sono trasmessi

costitutivamente promuovendo lrsquoinvasione la sopravvivenza e

lrsquoangiogenesi cellulare Le cellule tumorali trattate con

trastuzumab si arrestano in fase G1

Meccanismo di Resistenza

Il primo meccanismo di resistenza egrave quello dovuto alla induzione di p27kip1 un inibitore del cdk2 e della proliferazione cellulare che rimane nel citoplasma invece di traslocare nel nucleo Questo egrave causato dalla fosforilazione della Akt

Meta-analysis of all available studies based on 12 months of

trastuzumab showed that there was a statistically significant 30

relative improvement in overall survival using the 3-weekly regimen

INIBITORI DEI FATTORI DI CRESCITA

Erlotinib

LrsquoErlotinib egrave un farmaco usato nel trattamento del cancro al polmone a non piccole cellule cancro pancreatico e altri tipi di cancro

LrsquoEGFR (epidermal growth factor receptor) il recettore per il fattore di crescita epiteliale egrave presente sulla superficie cellulare Per la trasmissione del segnale due molecole di EGFR si debbono legare formando un dimero Attraverso lrsquouso di ATP questei due recettori si fosforilano e questa autofosforilazione porta ad una modificazione strutturale facendo partire tutta una cascata di eventi che portano lrsquoinformazione a livello nucleare per la replicazione cellulare

Lrsquo HER2neu (anche conosciuto come ErbB-2 che significa Epidermal growth factor Receptor 2) egrave una proteina con alta aggressivitagrave nel cancro della mammella HER2neu viene oggi codificato come CD340 e p185

Il fattore di crescita epiteliale

In biologia molecolare le chinasi regolate da segnali extracellulari (ERKs) dette anche MAP-chinasi sono largamente espresso a livello intracellulare dove sono coinvolte in funzioni quali la regolazione della meiosi mitosi e funzioni postmitotiche in cellule differenziate

LrsquoErlotinib egrave stato mostrato essere un forte inibitore dellrsquoattivitagrave dellrsquoenzima JAK2V617F Il JAK2V617F egrave una mutazione dellrsquoenzima tirosin chinasi ed egrave trovata in larga quantitagrave in pazienti con policitemia vera e in pazienti con mielofibrosi e trombocitopenia Studi recenti suggeriscono che lrsquoerlotinib puograve essere usato per il trattamento di malattie mieloproliferative e nella policitemia vera positiva al JAK2V617F

Meccanismo di Azione

Anticancer Res 2010 Apr30(4)1301-10Erlotinib in the treatment of non-small cell lung cancer current status and future developmentsGridelli C Maione P Bareschino MA Schettino C Sacco PC Ambrosio R Barbato V Falanga M Rossi ADivision of Medical Oncology SG Moscati Hospital Contrada Amoretta Avellino Italy cgridelliliberoitAbstractErlotinib is an orally small molecule inhibiting the tyrosine kinase activity of the epidermal growth factor receptor (EGFR) Currently erlotinib at a standard oral daily dose of 150 mg is licensed for the treatment of unselected recurrent non-small cell lung cancer (NSCLC) patients however it is being investigated in all stages of NSCLC Erlotinib is well tolerated with common toxicities including rash and diarrhoea The optimization of the therapeutic impact of erlotinib in NSCLC will be more defined when reliable predictive factors are identified An important step has been made in the molecular characterization of potentially sensitive NSCLC patients In fact we have learned that activation somatic EGFR gene mutations within the tyrosine kinase domain are associated with a high possibility of a long lasting therapeutic response to erlotinib The present review discusses the role of erlotinib in the treatment of NSCLC

Meccanismo di Resistenza

Il primo meccanismo di resistenza egrave quello dovuto alla induzione di p27kip1 un inibitore del cdk2 e della proliferazione cellulare che rimane nel citoplasma invece di traslocare nel nucleo Questo egrave causato dalla fosforilazione della Akt

Meta-analysis of all available studies based on 12 months of

trastuzumab showed that there was a statistically significant 30

relative improvement in overall survival using the 3-weekly regimen

INIBITORI DEI FATTORI DI CRESCITA

Erlotinib

LrsquoErlotinib egrave un farmaco usato nel trattamento del cancro al polmone a non piccole cellule cancro pancreatico e altri tipi di cancro

LrsquoEGFR (epidermal growth factor receptor) il recettore per il fattore di crescita epiteliale egrave presente sulla superficie cellulare Per la trasmissione del segnale due molecole di EGFR si debbono legare formando un dimero Attraverso lrsquouso di ATP questei due recettori si fosforilano e questa autofosforilazione porta ad una modificazione strutturale facendo partire tutta una cascata di eventi che portano lrsquoinformazione a livello nucleare per la replicazione cellulare

Lrsquo HER2neu (anche conosciuto come ErbB-2 che significa Epidermal growth factor Receptor 2) egrave una proteina con alta aggressivitagrave nel cancro della mammella HER2neu viene oggi codificato come CD340 e p185

Il fattore di crescita epiteliale

In biologia molecolare le chinasi regolate da segnali extracellulari (ERKs) dette anche MAP-chinasi sono largamente espresso a livello intracellulare dove sono coinvolte in funzioni quali la regolazione della meiosi mitosi e funzioni postmitotiche in cellule differenziate

LrsquoErlotinib egrave stato mostrato essere un forte inibitore dellrsquoattivitagrave dellrsquoenzima JAK2V617F Il JAK2V617F egrave una mutazione dellrsquoenzima tirosin chinasi ed egrave trovata in larga quantitagrave in pazienti con policitemia vera e in pazienti con mielofibrosi e trombocitopenia Studi recenti suggeriscono che lrsquoerlotinib puograve essere usato per il trattamento di malattie mieloproliferative e nella policitemia vera positiva al JAK2V617F

Meccanismo di Azione

Anticancer Res 2010 Apr30(4)1301-10Erlotinib in the treatment of non-small cell lung cancer current status and future developmentsGridelli C Maione P Bareschino MA Schettino C Sacco PC Ambrosio R Barbato V Falanga M Rossi ADivision of Medical Oncology SG Moscati Hospital Contrada Amoretta Avellino Italy cgridelliliberoitAbstractErlotinib is an orally small molecule inhibiting the tyrosine kinase activity of the epidermal growth factor receptor (EGFR) Currently erlotinib at a standard oral daily dose of 150 mg is licensed for the treatment of unselected recurrent non-small cell lung cancer (NSCLC) patients however it is being investigated in all stages of NSCLC Erlotinib is well tolerated with common toxicities including rash and diarrhoea The optimization of the therapeutic impact of erlotinib in NSCLC will be more defined when reliable predictive factors are identified An important step has been made in the molecular characterization of potentially sensitive NSCLC patients In fact we have learned that activation somatic EGFR gene mutations within the tyrosine kinase domain are associated with a high possibility of a long lasting therapeutic response to erlotinib The present review discusses the role of erlotinib in the treatment of NSCLC

INIBITORI DEI FATTORI DI CRESCITA

Erlotinib

LrsquoErlotinib egrave un farmaco usato nel trattamento del cancro al polmone a non piccole cellule cancro pancreatico e altri tipi di cancro

LrsquoEGFR (epidermal growth factor receptor) il recettore per il fattore di crescita epiteliale egrave presente sulla superficie cellulare Per la trasmissione del segnale due molecole di EGFR si debbono legare formando un dimero Attraverso lrsquouso di ATP questei due recettori si fosforilano e questa autofosforilazione porta ad una modificazione strutturale facendo partire tutta una cascata di eventi che portano lrsquoinformazione a livello nucleare per la replicazione cellulare

Lrsquo HER2neu (anche conosciuto come ErbB-2 che significa Epidermal growth factor Receptor 2) egrave una proteina con alta aggressivitagrave nel cancro della mammella HER2neu viene oggi codificato come CD340 e p185

Il fattore di crescita epiteliale

In biologia molecolare le chinasi regolate da segnali extracellulari (ERKs) dette anche MAP-chinasi sono largamente espresso a livello intracellulare dove sono coinvolte in funzioni quali la regolazione della meiosi mitosi e funzioni postmitotiche in cellule differenziate

LrsquoErlotinib egrave stato mostrato essere un forte inibitore dellrsquoattivitagrave dellrsquoenzima JAK2V617F Il JAK2V617F egrave una mutazione dellrsquoenzima tirosin chinasi ed egrave trovata in larga quantitagrave in pazienti con policitemia vera e in pazienti con mielofibrosi e trombocitopenia Studi recenti suggeriscono che lrsquoerlotinib puograve essere usato per il trattamento di malattie mieloproliferative e nella policitemia vera positiva al JAK2V617F

Meccanismo di Azione

Anticancer Res 2010 Apr30(4)1301-10Erlotinib in the treatment of non-small cell lung cancer current status and future developmentsGridelli C Maione P Bareschino MA Schettino C Sacco PC Ambrosio R Barbato V Falanga M Rossi ADivision of Medical Oncology SG Moscati Hospital Contrada Amoretta Avellino Italy cgridelliliberoitAbstractErlotinib is an orally small molecule inhibiting the tyrosine kinase activity of the epidermal growth factor receptor (EGFR) Currently erlotinib at a standard oral daily dose of 150 mg is licensed for the treatment of unselected recurrent non-small cell lung cancer (NSCLC) patients however it is being investigated in all stages of NSCLC Erlotinib is well tolerated with common toxicities including rash and diarrhoea The optimization of the therapeutic impact of erlotinib in NSCLC will be more defined when reliable predictive factors are identified An important step has been made in the molecular characterization of potentially sensitive NSCLC patients In fact we have learned that activation somatic EGFR gene mutations within the tyrosine kinase domain are associated with a high possibility of a long lasting therapeutic response to erlotinib The present review discusses the role of erlotinib in the treatment of NSCLC

LrsquoEGFR (epidermal growth factor receptor) il recettore per il fattore di crescita epiteliale egrave presente sulla superficie cellulare Per la trasmissione del segnale due molecole di EGFR si debbono legare formando un dimero Attraverso lrsquouso di ATP questei due recettori si fosforilano e questa autofosforilazione porta ad una modificazione strutturale facendo partire tutta una cascata di eventi che portano lrsquoinformazione a livello nucleare per la replicazione cellulare

Lrsquo HER2neu (anche conosciuto come ErbB-2 che significa Epidermal growth factor Receptor 2) egrave una proteina con alta aggressivitagrave nel cancro della mammella HER2neu viene oggi codificato come CD340 e p185

Il fattore di crescita epiteliale

In biologia molecolare le chinasi regolate da segnali extracellulari (ERKs) dette anche MAP-chinasi sono largamente espresso a livello intracellulare dove sono coinvolte in funzioni quali la regolazione della meiosi mitosi e funzioni postmitotiche in cellule differenziate

LrsquoErlotinib egrave stato mostrato essere un forte inibitore dellrsquoattivitagrave dellrsquoenzima JAK2V617F Il JAK2V617F egrave una mutazione dellrsquoenzima tirosin chinasi ed egrave trovata in larga quantitagrave in pazienti con policitemia vera e in pazienti con mielofibrosi e trombocitopenia Studi recenti suggeriscono che lrsquoerlotinib puograve essere usato per il trattamento di malattie mieloproliferative e nella policitemia vera positiva al JAK2V617F

Meccanismo di Azione

Anticancer Res 2010 Apr30(4)1301-10Erlotinib in the treatment of non-small cell lung cancer current status and future developmentsGridelli C Maione P Bareschino MA Schettino C Sacco PC Ambrosio R Barbato V Falanga M Rossi ADivision of Medical Oncology SG Moscati Hospital Contrada Amoretta Avellino Italy cgridelliliberoitAbstractErlotinib is an orally small molecule inhibiting the tyrosine kinase activity of the epidermal growth factor receptor (EGFR) Currently erlotinib at a standard oral daily dose of 150 mg is licensed for the treatment of unselected recurrent non-small cell lung cancer (NSCLC) patients however it is being investigated in all stages of NSCLC Erlotinib is well tolerated with common toxicities including rash and diarrhoea The optimization of the therapeutic impact of erlotinib in NSCLC will be more defined when reliable predictive factors are identified An important step has been made in the molecular characterization of potentially sensitive NSCLC patients In fact we have learned that activation somatic EGFR gene mutations within the tyrosine kinase domain are associated with a high possibility of a long lasting therapeutic response to erlotinib The present review discusses the role of erlotinib in the treatment of NSCLC

In biologia molecolare le chinasi regolate da segnali extracellulari (ERKs) dette anche MAP-chinasi sono largamente espresso a livello intracellulare dove sono coinvolte in funzioni quali la regolazione della meiosi mitosi e funzioni postmitotiche in cellule differenziate

LrsquoErlotinib egrave stato mostrato essere un forte inibitore dellrsquoattivitagrave dellrsquoenzima JAK2V617F Il JAK2V617F egrave una mutazione dellrsquoenzima tirosin chinasi ed egrave trovata in larga quantitagrave in pazienti con policitemia vera e in pazienti con mielofibrosi e trombocitopenia Studi recenti suggeriscono che lrsquoerlotinib puograve essere usato per il trattamento di malattie mieloproliferative e nella policitemia vera positiva al JAK2V617F

Meccanismo di Azione

Anticancer Res 2010 Apr30(4)1301-10Erlotinib in the treatment of non-small cell lung cancer current status and future developmentsGridelli C Maione P Bareschino MA Schettino C Sacco PC Ambrosio R Barbato V Falanga M Rossi ADivision of Medical Oncology SG Moscati Hospital Contrada Amoretta Avellino Italy cgridelliliberoitAbstractErlotinib is an orally small molecule inhibiting the tyrosine kinase activity of the epidermal growth factor receptor (EGFR) Currently erlotinib at a standard oral daily dose of 150 mg is licensed for the treatment of unselected recurrent non-small cell lung cancer (NSCLC) patients however it is being investigated in all stages of NSCLC Erlotinib is well tolerated with common toxicities including rash and diarrhoea The optimization of the therapeutic impact of erlotinib in NSCLC will be more defined when reliable predictive factors are identified An important step has been made in the molecular characterization of potentially sensitive NSCLC patients In fact we have learned that activation somatic EGFR gene mutations within the tyrosine kinase domain are associated with a high possibility of a long lasting therapeutic response to erlotinib The present review discusses the role of erlotinib in the treatment of NSCLC

LrsquoErlotinib egrave stato mostrato essere un forte inibitore dellrsquoattivitagrave dellrsquoenzima JAK2V617F Il JAK2V617F egrave una mutazione dellrsquoenzima tirosin chinasi ed egrave trovata in larga quantitagrave in pazienti con policitemia vera e in pazienti con mielofibrosi e trombocitopenia Studi recenti suggeriscono che lrsquoerlotinib puograve essere usato per il trattamento di malattie mieloproliferative e nella policitemia vera positiva al JAK2V617F

Meccanismo di Azione

Anticancer Res 2010 Apr30(4)1301-10Erlotinib in the treatment of non-small cell lung cancer current status and future developmentsGridelli C Maione P Bareschino MA Schettino C Sacco PC Ambrosio R Barbato V Falanga M Rossi ADivision of Medical Oncology SG Moscati Hospital Contrada Amoretta Avellino Italy cgridelliliberoitAbstractErlotinib is an orally small molecule inhibiting the tyrosine kinase activity of the epidermal growth factor receptor (EGFR) Currently erlotinib at a standard oral daily dose of 150 mg is licensed for the treatment of unselected recurrent non-small cell lung cancer (NSCLC) patients however it is being investigated in all stages of NSCLC Erlotinib is well tolerated with common toxicities including rash and diarrhoea The optimization of the therapeutic impact of erlotinib in NSCLC will be more defined when reliable predictive factors are identified An important step has been made in the molecular characterization of potentially sensitive NSCLC patients In fact we have learned that activation somatic EGFR gene mutations within the tyrosine kinase domain are associated with a high possibility of a long lasting therapeutic response to erlotinib The present review discusses the role of erlotinib in the treatment of NSCLC

Anticancer Res 2010 Apr30(4)1301-10Erlotinib in the treatment of non-small cell lung cancer current status and future developmentsGridelli C Maione P Bareschino MA Schettino C Sacco PC Ambrosio R Barbato V Falanga M Rossi ADivision of Medical Oncology SG Moscati Hospital Contrada Amoretta Avellino Italy cgridelliliberoitAbstractErlotinib is an orally small molecule inhibiting the tyrosine kinase activity of the epidermal growth factor receptor (EGFR) Currently erlotinib at a standard oral daily dose of 150 mg is licensed for the treatment of unselected recurrent non-small cell lung cancer (NSCLC) patients however it is being investigated in all stages of NSCLC Erlotinib is well tolerated with common toxicities including rash and diarrhoea The optimization of the therapeutic impact of erlotinib in NSCLC will be more defined when reliable predictive factors are identified An important step has been made in the molecular characterization of potentially sensitive NSCLC patients In fact we have learned that activation somatic EGFR gene mutations within the tyrosine kinase domain are associated with a high possibility of a long lasting therapeutic response to erlotinib The present review discusses the role of erlotinib in the treatment of NSCLC

The pharmacokinetic profile of erlotinib a lipophilic drug with poor solubility in water andmethanol has been extensively studied in adults After oral administration erlotinib exhibitedapproximately 60 bioavailability with administration with food enhancing bioavailabilityto upwards of 10026 Erlotinib was extensively bound to plasma proteins (95) and wassubject to extensive first-pass hepatic metabolism via the cytochrome P450 3A4 enzymeMetabolism produced several metabolites including the active metabolite O-desmethylerlotinib (OSI-420) and elimination occurs primarily via biliary excretion (63 feces vs 13urine) Maximum concentration of the drug (Cmax) was achieved 2ndash4 hours after doseadministration in adult patients with advanced malignant disease with a half-life ranging from10ndash36 hours The area under the curve (AUC) for erlotinib exhibited inter-patient variabilityand showed a non-linear dose relationship that has been described in several articles and studiesof adult cancer patients28

SummaryErlotinib a small-molecule epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor has been approved by FDA for patients with pancreatic cancer and non-small cell lung cancer Skin rash is a well-known side effect related with all EGFR blocking agents It has been suggested that rash could be used as a surrogate marker for response and possibly be associated with prolonged survival There is scant data reporting bacteremia secondary to severe erlotinib skin toxicity In this letter we report a case that developed systemic bacteremia while on erlotinib for treatment of advanced pancreatic cancer due to development of severe rash This case underlines the significance of potential severesystemic infection associated with erlotinib Previously there are many reports describing various skin toxicity manifestation however this is the second case in English literature which had systemic Staphylococcus aureus bacteremia arising from erlotinib skin toxicity Monitor patients closely after starting EGFR blocking agents and initiate immediate skin care based on general guideline are highly recommended

Over the last years new agents have been introduced for the treatment of metastatic colorectal cancer the main objective being to prolong patient survival One of these agents is bevacizumab (Avastin Genetech Inc) a monoclonal antibody a diffusible endothelial-specific mitogen and an antibody to vascular endothelial growth factor (VEGF) VEGF is a secreted ligand that binds to specific receptors expressed by angioblasts and endothelial cells

The VEGF receptor (VEGFR) family ligands VEGF-1 and VEGF-2 are biologically related to angiogenesis and VEGF-c and D-VEGFR-3 are associated with lymphangiogenesis Tumor angiogenesis is complex in that many cell types and factors are involved ie such as platelet-derived growth factor b-fibroblast growth factor VEGFA HGF TGFa and EGF The characteristics of the tumor and its environment promote VEGF expression VEGF is overexpressed in a good number of human malignancies and it is considered to be an important regulator of physiologic and pathologic angiogenesis

The vascular endothelial growth factor (VEGF)

Oncology 201078376ndash381

Panitumumab is the first fully human anti-EGFR monoclonal antibody and is a very promising new treatment option for patients with KRAS wild-type metastatic colorectal carcinoma The efficacy of panitumumab monotherapy has been demonstrated in the pivotal open label phase III study in which panitumumab significantly prolonged progression-free survival versus best supportive care in patients with wild-type KRAS tumors refractory to standard chemotherapeutic agents

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SummaryErlotinib a small-molecule epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor has been approved by FDA for patients with pancreatic cancer and non-small cell lung cancer Skin rash is a well-known side effect related with all EGFR blocking agents It has been suggested that rash could be used as a surrogate marker for response and possibly be associated with prolonged survival There is scant data reporting bacteremia secondary to severe erlotinib skin toxicity In this letter we report a case that developed systemic bacteremia while on erlotinib for treatment of advanced pancreatic cancer due to development of severe rash This case underlines the significance of potential severesystemic infection associated with erlotinib Previously there are many reports describing various skin toxicity manifestation however this is the second case in English literature which had systemic Staphylococcus aureus bacteremia arising from erlotinib skin toxicity Monitor patients closely after starting EGFR blocking agents and initiate immediate skin care based on general guideline are highly recommended

Over the last years new agents have been introduced for the treatment of metastatic colorectal cancer the main objective being to prolong patient survival One of these agents is bevacizumab (Avastin Genetech Inc) a monoclonal antibody a diffusible endothelial-specific mitogen and an antibody to vascular endothelial growth factor (VEGF) VEGF is a secreted ligand that binds to specific receptors expressed by angioblasts and endothelial cells

The VEGF receptor (VEGFR) family ligands VEGF-1 and VEGF-2 are biologically related to angiogenesis and VEGF-c and D-VEGFR-3 are associated with lymphangiogenesis Tumor angiogenesis is complex in that many cell types and factors are involved ie such as platelet-derived growth factor b-fibroblast growth factor VEGFA HGF TGFa and EGF The characteristics of the tumor and its environment promote VEGF expression VEGF is overexpressed in a good number of human malignancies and it is considered to be an important regulator of physiologic and pathologic angiogenesis

The vascular endothelial growth factor (VEGF)

Oncology 201078376ndash381

Panitumumab is the first fully human anti-EGFR monoclonal antibody and is a very promising new treatment option for patients with KRAS wild-type metastatic colorectal carcinoma The efficacy of panitumumab monotherapy has been demonstrated in the pivotal open label phase III study in which panitumumab significantly prolonged progression-free survival versus best supportive care in patients with wild-type KRAS tumors refractory to standard chemotherapeutic agents

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Over the last years new agents have been introduced for the treatment of metastatic colorectal cancer the main objective being to prolong patient survival One of these agents is bevacizumab (Avastin Genetech Inc) a monoclonal antibody a diffusible endothelial-specific mitogen and an antibody to vascular endothelial growth factor (VEGF) VEGF is a secreted ligand that binds to specific receptors expressed by angioblasts and endothelial cells

The VEGF receptor (VEGFR) family ligands VEGF-1 and VEGF-2 are biologically related to angiogenesis and VEGF-c and D-VEGFR-3 are associated with lymphangiogenesis Tumor angiogenesis is complex in that many cell types and factors are involved ie such as platelet-derived growth factor b-fibroblast growth factor VEGFA HGF TGFa and EGF The characteristics of the tumor and its environment promote VEGF expression VEGF is overexpressed in a good number of human malignancies and it is considered to be an important regulator of physiologic and pathologic angiogenesis

The vascular endothelial growth factor (VEGF)

Oncology 201078376ndash381

Panitumumab is the first fully human anti-EGFR monoclonal antibody and is a very promising new treatment option for patients with KRAS wild-type metastatic colorectal carcinoma The efficacy of panitumumab monotherapy has been demonstrated in the pivotal open label phase III study in which panitumumab significantly prolonged progression-free survival versus best supportive care in patients with wild-type KRAS tumors refractory to standard chemotherapeutic agents

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Panitumumab is the first fully human anti-EGFR monoclonal antibody and is a very promising new treatment option for patients with KRAS wild-type metastatic colorectal carcinoma The efficacy of panitumumab monotherapy has been demonstrated in the pivotal open label phase III study in which panitumumab significantly prolonged progression-free survival versus best supportive care in patients with wild-type KRAS tumors refractory to standard chemotherapeutic agents

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