Efficacy and safety of pharmacological interventions in second- or later-line treatment of patients with advanced soft tissue sarcoma: a systematic review.
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.
Heron Health Pvt. Ltd., Chandigarh, India.
Sheetal
S
Sharma
Shweta
S
Takyar
Stephanie C
SC
Manson
Sarah
S
Powell
Nicolas
N
Penel
D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D003606:Dacarbazine / Q000009:adverse effects / Q000627:therapeutic use; D003841:Deoxycytidine / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D004149:Dioxoles / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D007191:Indazoles; D011743:Pyrimidines / Q000009:adverse effects / Q000627:therapeutic use*; D016032:Randomized Controlled Trials as Topic; D012509:Sarcoma / Q000188:drug therapy*; D013449:Sulfonamides / Q000009:adverse effects / Q000627:therapeutic use*; D044005:Tetrahydroisoquinolines / Q000009:adverse effects / Q000627:therapeutic use; D000077606:Trabectedin; D017211:Treatment Failure; D000093542:Gemcitabine
D000970:Antineoplastic Agents; D004149:Dioxoles; D007191:Indazoles; D011743:Pyrimidines; D013449:Sulfonamides; D044005:Tetrahydroisoquinolines; D003841:Deoxycytidine; D003606:Dacarbazine; C516667:pazopanib; D000077606:Trabectedin; D000093542:Gemcitabine