A phase II trial of panobinostat in patients with advanced pretreated soft tissue sarcoma. A study from the French Sarcoma Group

Br J Cancer. 2013 Aug 20;109(4):909-14. doi: 10.1038/bjc.2013.442. Epub 2013 Aug 6.

Abstract

Background: Soft tissue sarcomas (STS) are rare tumours for which treatment options are limited in the advanced setting. Histone deacetylase inhibitors have shown activity in preclinical models of STS.

Methods: We conducted a single-arm, open-label, multicentre phase II study to assess the efficacy and tolerability of panobinostat given orally, 40 mg thrice weekly in patients with advanced pretreated STS. The primary endpoint was the 3-month progression-free rate.

Results: Forty-seven STS patients were enrolled between January 2010 and December 2010. Median age was 59 (range 21-79) years, 22 (47%) patients were males. Panobinostat dose was lowered to 20 mg thrice weekly after nine patients were enrolled, based on the recommendation of an independent safety committee. The most common grade 3/4 adverse events were thrombocytopenia, fatigue, lymphopenia and anaemia. Forty-five patients were evaluable for the primary endpoint. Among them, nine patients (20%, 95% CI (10-35%)) were progression-free at 3 months. No partial response was seen, but 17 patients (36%) had stable disease (SD) as their best response. Six patients were progression-free at 6 months.

Conclusion: Panobinostat was poorly tolerated at 40 mg thrice a week. Efficacy in unselected advanced STS was limited, although some patients had prolonged SD.

Trial registration: ClinicalTrials.gov NCT01136499.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / therapeutic use*
  • Disease-Free Survival
  • Female
  • Humans
  • Hydroxamic Acids / therapeutic use*
  • Indoles / therapeutic use*
  • Leiomyosarcoma / drug therapy
  • Leiomyosarcoma / pathology
  • Liposarcoma / drug therapy
  • Liposarcoma / pathology
  • Liposarcoma, Myxoid / drug therapy
  • Liposarcoma, Myxoid / pathology
  • Male
  • Middle Aged
  • Nerve Sheath Neoplasms / drug therapy
  • Nerve Sheath Neoplasms / pathology
  • Panobinostat
  • Salvage Therapy / methods
  • Sarcoma / drug therapy*
  • Sarcoma / pathology
  • Sarcoma, Alveolar Soft Part / drug therapy
  • Sarcoma, Alveolar Soft Part / pathology
  • Sarcoma, Endometrial Stromal / drug therapy
  • Sarcoma, Endometrial Stromal / pathology
  • Sarcoma, Synovial / drug therapy
  • Sarcoma, Synovial / pathology
  • Treatment Outcome
  • Young Adult

Substances

  • Antineoplastic Agents
  • Hydroxamic Acids
  • Indoles
  • Panobinostat

Associated data

  • ClinicalTrials.gov/NCT01136499