Intraperitoneale Ozone therapy in advanced cancer

patients – First Experiences

R. Kleef, WienInstitut für Wärme und Immuntherapie

Ozone or trioxygen (O3)

The Marburg Paper …

Schulz S, Häussler U, Mandic R, Heverhagen JT, Neubauer A, Dünne AA, Werner JA, Weihe

E, Bette M. Treatment with ozone/oxygen-pneumoperitoneum results in complete

remission of rabbit squamous cell carcinomas. Int J Cancer. 2008 May 15;122(10):2360-7

Schulz et al. 2008

Prequisition

• Informed consent• Clear inclusion/exclusion criteria• Surgical implantation of ip-catheter• Individualized analgesia/sedation • Excellent patient monitoring• Proper documentation and follow up

(blood work up, radiology work up)

Informed consent !

Patient characteristics

Total # of pat. 10 # of treaments/indicationMelanoma 3 24Ovarian cancer 2 16Vaginal cancer 1 8Penis cancer 1 8Prostate cancer 1 10Leiomyo-sarkom 1 12Papilla vateri carcinoma 1 5

Total # of treaments 83

Name Alter Diagnosis Metastasis 1st diagn. Karnofsky Beginn Ozon ip # treatm. 1. Re

staging Result

KF 64 Penis carcinom

Pulmo, inguinal

Feb. 07 50% Okt. 08 8 Dez 08 PD

HS 44 Ovarial carcinom

Peritoneal carcinose

Jan. 98 70% Sep. 08 10 Okt 08 PR/SD

WR 53 Melanom Lymphangiosis

Dez. 06 80% Okt. 08 11 Dez 08 PR

FF 63 MelanomLungen,

Leber, NN, Knochen

Sep. 04 60% Okt. 08 5 Dez 08 PD

McGD 55 Vaginal carcinom

Lungen Leber

Adenexe Nov. 99 60% Nov. 08 8 Dez 08 PD

HE 54 Ovarial carcinom

Peritoneal carcinose

Feb. 03 90% Nov. 08 6 Dez 08 SD

PZ 47 P. Vateri Carcinom

Liver Sep. 07 50% Nov. 08 5 Dez 08 PD

PC 46 Melanom Lunge, Herz Jun. 05 70% Nov. 08 8 Dez 08 PD

SJ 44 Leiomyo-sarkom

Mediastinum Pulmo

Jun. 06 70% Dez. 08 12 Mrz 09 PD

SH 55 Prostata-carcinom Bone Dez 08 90% Feb 09 10 Mrz. 09 PD

ResponseMelanoma PR 1Ovarian cancer SD 1Ovarian cancer PD 1Melanoma PD 2Vaginal cancer PD 1Penis cancer PD 1Prostate cancer PD 1Leiomyo-sarkom PD 1Papilla vateri carcinoma PD 1Summary PD 8

SD 1PR 1

Quality of life

Melanoma PD ---Melanoma PD +++Melanoma SD +++Ovarian cancer PD + -Ovarian cancer PR +++Vaginal cancer PD ++Penis cancer PD +Prostate cancer PD +Papilla vateri carcinoma PD --

Melanoma PD --- 5 treatments

63y old male patient with far advanced melanoma disseminated metastatic to adrenal glands, lungs, multiple bone mets: Karnofsky 60%

Heavily pretreated with high dose Interferon and multiple CHTs

Epicrisis: hospitalization & blood transfusion necessary, febrile, Karnofsky 50%

Melanoma PR +++11 Treatments

53y old male patient with melanoma, lymphatic metastasis to the right leg, leg swollen with 100% increase in circumference: Karnofsky 80%

No pretreatment Epicrisis: good clinical condition, PET confirms

clear PR, Karnofsky 90%

Before treatment 9/2008

11/2008

12/2008

01/2009

End treatment 4/2009

Melanoma PD +++6 Treatments

46y old male patient with melanoma 1st diagnosed 01/2001, 9/2008 Reoccurrence in the left lung with a large mass of 10.4x5.6cm and a PET SUV of 17.2 directly infiltrating the cardiac muscle (left and right ventricle) and the diaphragm enclosing the n. phrenicus. Disseminated Liver mets. The mass was biopsy proven to be metastatic melanoma, Karnofsky 50%

No pretreatment , inoperable Epicrisis: clear improvement of QoL, better clinical condition,

Karnofsky 80%, died 3 weeks later

Ovarian cancer SD + - 10 Treatments

44y old female patient with ovarian cancer 1st diagnosed 01/2007, breast cancer with bil. Ablatio 1998), 9/2008: Karnofsky 50%

Heavily pretreated with multiple CHTs Epicrisis: dramatic improvement of QoL, better

clinical condition, Karnofsky 80%. Initial clear remission of TM, after 4 weeks however PD of TM, now in SD under low dose carboplatin

Ovarian cancer PD + -

16.09.08 25.09.08 26.09.08 01.10.08 06.10.08 13.10.08 20.10.08 27.10.08 04.11.08 12.11.08 24.11.08 27.11.08 05.12.081. IPO 2. IPO Carbo ip

CA 19-9 52CA 125 940 377 345 316 318 307 340 406 743 1183CA15-3 109 67 57 52

GGT 96 99 108 99 86 68 71 65 72 49BSG1 64 85 53 49 39 44 52 41 8 43 81BSG2 89 109 78 74 63 69 77 65 21 68 122ERY 4 4 3,53 3,44 3,22 2,83 2,74 2,64 3,18 3,8 3,42HB 12 12 10,30 9,70 9,10 7,80 7,80 7,00 9,30 11,20 10,90

Thrombo 458 400 341 333 405 458 481 527 308 370 302LDH 197 176 214 216 214 200 220 253 237 252 236

Leuko 5380 6600 6070 6630 6800 6140 5990 6640 4520 6110 5100Lympho 2281 1808 2343 2377 2088 2388 1953 2138 1505 1705

CRP 0,1 22,0 5,8 1,7 0,8 3,7 2,7 1,0 1,1 3,3 7,0

HS 29.07.64 Ovarialcarcinom

Ovarian cancer PD +++ 6 treatments

54y old female patient with ovarian cancer 1st diagnosed 02/2003, 9/2008: massive Peritoneal carcinosis, liver metastasis, Karnofsky 80%

Heavily pretreated with multiple CHTs Epicrisis: dramatic improvement of QoL, better

clinical condition, Karnofsky 90%. Transient TM remission, died 05/2009

17.11.08 19.11.08 24.11.08 10.12.081. IPO

CA 125 494 394 438 582GGT 40 34 39 34BSG1 60 52 63BSG2 85 77 88ERY 3,43 2,91 3,65 3,94HB 10,00 8,30 10,40 11,30

Thrombo 247 195 218 178LDH 198 164 221 230

Leuko 3740 2240 3810 2990Lympho 741 739 667 945

CRP 14 19 91 10,3

HE 29.11.54 Ovarialcarcinom

Vaginal cancer PD ++ 8 treatments

55y old female patient with far advanced vaginal cancer 1st diagnosed 11/1999, 2/2008 massive local Reoccurrence, small liver/lung mets. Karnofsky 50%

Heavily pre-radiated, inoperable Epicrisis: dramatic improvement of QoL, better

clinical condition, new DVT, Karnofsky 80%

Penis cancer PD +- 8 treatments

64y old male patient with far advanced penis cancer 1st diagnosed 02/2007, Penisamputation and bilateral radiation of the inguinal region with 70Gy. 4/2008 Reoccurrence in both groins with massive lymphatic metastasis. The masses caused severe lymph edema of both lower extremities, Karnofsky 50%

Radiation pretreatment, inoperable Epicrisis: only slight improvement of QoL/clinical

condition, Karnofsky 50%, died 12/2008

Papilla vateri carcinoma PD --

47y old female patient with far advanced hepatic metastasized papilla vateri carcinoma 1st diagnosed 09/2007, Duodenopancreatectomie und atypical liver resection, 9/2008 massive PD with increase of liver mets and large reoccurrence in epigastrium, Karnofsky 50%

Discontinuation of CHT (Xeloda/Oxaliplatin) due to massive SE

Epicrisis: No improvement of QoL, devlp. of massive deep vein thrombosis in 4 levels, initiation of anticoagulant therapy, died 12/2008

Summary & Conclusion 1

• Clear indication for improved QoL• Response also in far advanced cancer patients

in some cases • Challenging and complex method with high

personal and time input• Many open questions as to which is the best

interval to repeat the treatment and which are the mechanisms of action

Summary & Conclusion 2

• We may see an increased risk of the development of deep vein thrombosis !

• Prophylactic anticoagulant therapy is highly recommended (Lovenox40 1x/dayly) pre- and post treatment

• Melanoma

Where do we go from here ?

1. Identify and treat newly diagnosed melanoma (CHT- and IFN-naive)

2. Plan trials for combination with (low-dose) chemotherapy

Biomarker to be tested

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Thank you for your attention