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

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BMC Cancer

, 13:385

Clinical oncology


BackgroundCurrent 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.

MethodsElectronic 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.

ResultsThe 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.

ConclusionsAcross 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.

KeywordsSystematic review Pazopanib Soft tissue sarcoma AbbreviationsAEAdverse event

ALTAlanine aminotransferase

ASTAspartate aminotransferase

CRComplete response

DORDuration of response

GISTGastrointestinal stromal tumour

ORROverall response rate

OSOverall survival

PDProgressive disease

PFSProgression-Free survival

PRPartial response

PRISMAPreferred reporting items for systematic reviews and meta-analyses

RCTSRandomised controlled trials

SDStable disease

STSSoft tissue sarcoma

TTPTime to progression

TTRTime to response.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2407-13-385 contains supplementary material, which is available to authorized users.

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Author: Sheetal Sharma - Shweta Takyar - Stephanie C Manson - Sarah Powell - Nicolas Penel

Source: https://link.springer.com/

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