Efficacy and safety of pharmacological interventions in second- or later-line treatment of patients with advanced soft tissue sarcoma: a systematic review

BMC Cancer. 2013 Aug 13:13:385. doi: 10.1186/1471-2407-13-385.

Abstract

Background: Current guidelines recommend anthracycline-based chemotherapy primarily with doxorubicin either as monotherapy or in combination with ifosfamide as the first-line treatment for most advanced STS subtypes. Therapeutic options after failure of doxorubicin and/or ifosfamide are limited. This study aimed to comprehensively review available data on the activity and safety of interventions in second- or later-line treatment of advanced STS.

Methods: Electronic literature databases (Embase®, MEDLINE®, MEDLINE® In-Process, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews) were searched from 1980 to 01 March 2012 to identify randomised controlled trials (RCTs) and non-randomised studies (both prospective and retrospective) evaluating pharmacological interventions in patients with advanced STS pre-treated with anthracycline- and/or ifosfamide-based therapy.

Results: The review identified six RCTs (one phase III and five phase II trials) and 94 non-randomised studies. Based on the primary trial endpoints, RCTs demonstrated favourable efficacy for pazopanib over placebo (PFS: 4.6 months vs. 1.6 months), gemcitabine plus dacarbazine over dacarbazine monotherapy (3-month PFS rate: 54.2% vs. 35.2%), and trabectedin 3-weekly schedule over weekly schedule (TTP: 3.7 months vs. 2.3 months. The non-randomised studies demonstrated heterogeneity in efficacy and safety results.

Conclusions: Across the RCTs, pazopanib over placebo, gemcitabine-dacarbazine over dacarbazine, and trabectedin 3-weekly over weekly regimen clearly demonstrated a PFS advantage in the second- and later-line treatment of advanced STS. With only one phase III trial in this setting, there is a clear need for additional comparative trials to better understand the risk: benefit ratios of available agents and combinations.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Dacarbazine / adverse effects
  • Dacarbazine / therapeutic use
  • Deoxycytidine / adverse effects
  • Deoxycytidine / analogs & derivatives
  • Deoxycytidine / therapeutic use
  • Dioxoles / adverse effects
  • Dioxoles / therapeutic use
  • Gemcitabine
  • Humans
  • Indazoles
  • Pyrimidines / adverse effects
  • Pyrimidines / therapeutic use*
  • Randomized Controlled Trials as Topic
  • Sarcoma / drug therapy*
  • Sulfonamides / adverse effects
  • Sulfonamides / therapeutic use*
  • Tetrahydroisoquinolines / adverse effects
  • Tetrahydroisoquinolines / therapeutic use
  • Trabectedin
  • Treatment Failure

Substances

  • Antineoplastic Agents
  • Dioxoles
  • Indazoles
  • Pyrimidines
  • Sulfonamides
  • Tetrahydroisoquinolines
  • Deoxycytidine
  • Dacarbazine
  • pazopanib
  • Trabectedin
  • Gemcitabine