Alterazioni elettrolitiche - NICSO - NetAlterazioni elettrolitiche Rossana Berardi, Ancona Rossana...

Alterazioni elettrolitiche

Rossana Berardi, Ancona

Rossana Berardi - Grandangolo in Oncologia. Focus su terapie di supporto 2016 - Bologna, 9 maggio 2016

Disordini elettrolitici in corso di terapia anti-EGFR

> Panitumumab vs. Cetuximab

> Nuovi anti-EGFR (Sym004)


Nuovo modello prognostico nel mRCC trattato con targeted therapy IPERCALCEMIA

Derosa L et al. ESMO 2015


Idratazione

Diuretici in base al volume

Bifosfonati, denosumab


43 pazienti con mCRC trattati con cetuximab o panitumumab.

Incidenza ipomagnesemia da anti-EGFR 32.6%

Correlazione con risposta!

52 pazienti con mCRC trattati con cetuximab.

Incidenza ipomagnesemia 29.6%

No correlazione con età.


Ipomagnesemia effetto di classe (anti-EGFR)

reversibile dopo settimane/mesi

Pertuzumab (>G1 = 14%) ≠ Trastuzumab

Studio ongoing prospettico per confermare

ipomagnesemia da pertuzumab in ca mammario HER-2+

Mancano studi prospettici per la terapia

dell’ipomagnesemia (supplementazione per os inefficace)


Ipomagnesemia da panitumumab: frequente e correla con outcome!

Peeters M et al. ASCO GI 2016


Iponatremia in oncologia: uno scenario in evoluzione

IERI…

Disorder Prevalence (%)

Intensive care patients 11–29.6

Elderly outpatients 7.2–11

Elderly inpatients 18–53

Heart failure 10.2–27

Cirrhosis 20.8–49.4

Cancer 3.7–47

Patients with pneumonia 8.1–27.9

Chronic kidney disease 13.6

Dialysis patients 29.3

Elderly patients with falls 9.1–13

Marathon runners 3–13


Rates of hyponatremia in different cancers


Surv

ival

pro

bab

ility

(%

) Time

Sodium ≥135 mEq/L

Sodium <135 mEq/L

Hyponatraemia is associated with poor

treatment outcomes in mesothelioma patients

Berardi R et al. Supp Care Cancer 2015


Risk factors in patients with cancer


Essential criteria for the diagnosis of SIADH

• Hyponatraemia <135 mmol/L

• Plasma hypo-osmolality <275 mOsm/kg

• Urine osmolality >100 mOsm/kg

• Clinical euvolaemia

• No clinical signs of hypovolaemia (orthostatic decreases

in blood pressure, tachycardia, decreased skin turgor,

dry mucous membranes)

• No clinical signs of hypervolaemia (oedema, ascites)

• Increased urinary sodium excretion >40 mmol/L

with normal salt and water intake

• Absence of other potential causes of euvolaemic

hypo-osmolality

• Exclude recent diuretic use, renal disease, hypothyroidism

and hypocortisolism

1. Ellison DH, et al. N Engl J Med 2007;356:2064–2072.

2. Verbalis J, et al. Am J Med 2013;126(10 Suppl 1):S1–S42.


SIADH: treatment options

Therapeutic strategies should include the removal of the cause,

whenever possible, together with the correction of sodium imbalance

DI, diabetes insipidus; SIADH, syndrome of inappropriate antidiuretic hormone secretion

Peri A, et al. J Endocrinol Invest 2010;33:671–682.

Treatment Notes

Fluid restriction ± furosemide First-line approach in asymptomatic patients

Uncomfortable for the patients

Hypertonic saline (3% NaCl) ± furosemide First-line approach in symptomatic patients

Demeclocycline * Nephrogenic DI (60%)

Treatment must be continued for several days because the

onset of action is delayed and up to 2 weeks may be

necessary to restore normal plasma [Na+]

Several side effects (nephrotoxicity)

Lithium* Nephrogenic DI (30%)

Several side effects (nephrotoxicity, hypothyroidism)

Urea * Poor palatability

Development of uraemia at higher doses

Gastrointestinal symptoms

Tolvaptan For the treatment of hyponatraemia due to SIADH


Aim of study: To investigate incidence and relative risk of hyponatraemia in

cancer patients treated with targeted therapies through an up-to-date

meta-analysis of available clinical trials

Berardi R, et al. Oral presentation at MASCC 2015, Oral presentation at IASLC 2015, PlosOne accepted for publication

The scientific literature regarding

hyponatraemia was extensively

reviewed using MEDLINE and

PubMed databases. Eligible

studies were selected according

to PRISMA statement.

Jadad score (mean):

3.7 (range 3–5)

Risk of hyponatraemia in cancer patients treated with targeted

therapies: systematic review and meta-analysis


Risk of all-grade hyponatraemia with targeted agents

Berardi R, et al. Oral presentation at MASCC 2015, Oral presentation at IASLC 2015, PlosOne accepted for publication

Risk of high-grade hyponatraemia with targeted agents

Brivanib (RR=5.2), sorafenib (RR=2.4), vorinostat (RR=2.1)

anti-VEGF (RR=2.69) – anti-EGFR (RR=1.12)

Risk of hyponatraemia in cancer patients treated with targeted

therapies: systematic review and meta-analysis


Survival time, months

Normalised to

136 + mEq/L

Not normalised

to 136 mEq/L

100

40

30

20

10

0 0 24

Normalised

Not Normalised

50 60

70

80

90 S

urv

iva

l, %

12

Hansen O, et al. Lung Cancer 2010;68:111–114.

Crude survival of 61 evaluable patients with SCLC with [Na+] <

130 mmol/L receiving two or more cycles of chemotherapy,

split into the 15 patients who normalised their sodium and the

46 patients who did not (p=0.027)

Hyponatraemia correction and prognosis in SCLC


Berardi et al, submitted

Italy-UK collaboration

mOS = 16 vs. 9 months, p=0.0007

Hyponatremia and outcome in NSCLC: 433 patients


Survival is the main, but not the only reason to treat SIADH…

Impact on patients’ QoL

and well-being

Increase of length of

hospitalization and readmission

rates

Delay of anticancer treatment

Costs increase


COSTS: 128% FOR

MODERATE HN 299% FOR SEVERE HN

Berardi et al, Supp Care Cancer 2015

Hyponatremia is a predictor of hospital length and cost of stay


Patient and disease characteristics at admission

SIADH, syndrome of inappropriate antidiuretic hormone secretion

De Las Peñas R, et al. Support Care Cancer 2016;24:499–507.

Patients N=35

Days to restore natraemia, n (%)

1–4 days

>4 days

Partial response

No response

18 (51)

13 (37)

3 (9)

1 (3)

Adverse events reported, n

Thirst

Polyuria

Dry mouth

Hepatic enzymes elevation

Others

Mild

9

6

4

2

0

Moderate

3

4

0

0

0

Severe

0

0

0

0

0


SIADH-related hyponatraemia in hospital day care units: clinical experience with tolvaptan

Treatment algorithm for hyponatraemia in cancer patients



1. Administer tolvaptan until improvement in natraemia and then start chemotherapy. Can be administered jointly with chemotherapy under strict control of diuresis

2. Patient weight mL/h of SS 3%; with control of plasma [Na+] every 2 hours at start


SIADH-related hyponatraemia in hospital day care units: clinical experience with tolvaptan

Treatment algorithm for hyponatraemia in cancer patients



1. Patients candidates for endocrine, biological, immune therapy, or exclusive symptomatic treatment

2. Patient weight mL/h of SS 3%; with control of plasma [Na+] every 2 hours at start

*Support treatments: fluid restriction; salt supplements


ASSERT TRIAL: A prospective, observational study measuring

sodium improvement and outcomes in cancer patients treated for

moderate to severe hyponatremia secondary to SIADH

Lo studio si propone di raccogliere informazioni

scientifiche che aiutino a descrivere le caratteristiche dei

pazienti oncologici con SIADH, di definire le terapie per

correggere l’iponatremia nell’ambito della pratica clinica e di

validare/modificare le raccomandazioni attuali

Disegno dello studio

Osservazionale, prospettico, non interventistico, multicentrico

Centri partecipanti: 24 Centri Italiani

Dimensioni del campione: 80 pazienti (previsti 100 pazienti arruolati,

considerando dropout del 20%)


Further improvements to be anticipated… - Prospective studies - Attention to standard cancer treatments

and newer targeted agents - Management strategies


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