panobinostat (FARYDAK°). Multiple myeloma: too toxic!

Publisher: Association Mieux Prescrire Country of Publication: France NLM ID: 9439295 Publication Model: Print Cited Medium: Print ISSN: 1167-7422 (Print) Linking ISSN: 11677422 NLM ISO Abbreviation: Prescrire Int

Original Publication: Paris : Association Mieux Prescrire, [1992-

Antineoplastic Agents/*adverse effects ; Multiple Myeloma/*drug therapy ; Panobinostat/*adverse effects; Antineoplastic Agents/therapeutic use ; Arrhythmias, Cardiac/chemically induced ; Chemical and Drug Induced Liver Injury/etiology ; Cost-Benefit Analysis ; Diarrhea/chemically induced ; Drug Interactions ; Gastrointestinal Diseases/chemically induced ; Hemorrhage/chemically induced ; Humans ; Hypothyroidism/chemically induced ; Infections/etiology ; Mortality ; Multiple Myeloma/mortality ; Myocardial Ischemia/chemically induced ; Neutropenia/chemically induced ; Panobinostat/therapeutic use ; Progression-Free Survival ; Renal Insufficiency/chemically induced ; Survival Rate ; Thrombocytopenia/chemically induced

Patients with relapsed or refractory multiple myeloma who have received several lines of therapy have no satisfactory treatment options. High-dose corticosteroid therapy or a combination of low-dose dexamethasone and pomaildomide may be proposed. Panobinostat is the first histone deacetylase (HDAC) inhibitor to be authorised in the European Union for use in this indication. A randomised, double-blind, placebo-controlled trial evaluated panobinostat in 768 patients with relapsed or refractory multiple myeloma who were also receiving bortezomib + dexamethasone. Panobinostat did not prolong survival. The median time to myeloma progression, relapse, or death was prolonged by about 3 months with the panobinostat-containing combination, and by a median of about 8 months in the subgroup of patients who had received at least two lines of chemotherapy including bortezomib and an "immunomodulatory" drug. There was no statistically significant increase in survival, however. In this trial, adverse events led one in six patients to discontinue panobinostat and resulted in numerous hospital admissions. The proportion of patients who died from causes unrelated to myeloma was 6.8% in the panobinostat group versus 3.2% In the placebo group. The toxicity of panobinostat affects most vital functions, resulting in a risk of infections as well as haematological, gastrointestinal, cardiac, renal, hepatic and thyroid disorders. These adverse effects are often severe and sometimes fatal. Panobinostat is subject to pharmacokinetic interactions via cytochrome P450 enzymes and P-glycoproteln, and also to pharmacodynamic Interactions. Panobinostat was teratogenic in animal studies. In practice, even when several previous lines of treatment have failed, panobinostatis more toxic than useful In patients with myeloma. It should therefore not be used.

0 (Antineoplastic Agents)
9647FM7Y3Z (Panobinostat)

Date Created: 20190205 Date Completed: 20190312 Latest Revision: 20191210

20231215

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