Multi-agent chemotherapy in advanced soft tissue sarcoma (STS) - A systematic review and meta-analysis.
BACKGROUND
Despite a lack of improvement in overall survival (OS) with doxorubicin-based combinations over doxorubicin alone in advanced STS, the role of multi-agent chemotherapy remains poorly defined.


METHODS
We conducted a systematic review and meta-analysis to evaluate benefits and harms of multi-agent chemotherapy in advanced STS. Eligible studies were randomized trials of chemotherapy in advanced STS comparing single agent to multi-agent therapy. Data from studies reporting a hazard ratio (HR) and 95% confidence intervals (CI) for OS and progression-free survival (PFS) were pooled in a meta-analysis. Meta-regression was utilized to explore the association between efficacy (OS and PFS) and both toxicity and dose intensity.


RESULTS
We identified 22 trials published between 1974 and April 2016 and comprising 5044 patients. Overall, multi-agent chemotherapy was associated with improved OS (HR:0.79, p = 0.02), and borderline improvement in PFS (HR:0.86, p = 0.05). While the effect on OS was similar in trials with non-anthracycline controls compared to those with anthracycline controls (HR for OS 0.73 vs. 0.82, p for difference = 0.63) there was a non-significantly greater effect for multi-agent chemotherapy on PFS in non-anthracycline RCT (HR for PFS 0.73 vs. 0.91, p for difference = 0.13). Compared to studies with cytotoxic therapy-based multi-agent therapy, a non-significantly greater magnitude of effect among studies with biological/cytostatic experimental groups was seen (HR for OS 0.64 vs. 0.86, p for difference = 0.37). There was a borderline significant association between dose reductions (which were more common in combination arms) and worse PFS (beta = 0.70, p = 0.053).


CONCLUSION
Multi-agent chemotherapy is associated with a modest, but statistically significant improvement in outcomes in STS. Combining chemotherapy with non-cytotoxic agents might represent a promising strategy.
['Zer|Alona|A|', 'Prince|Rebecca M|RM|', 'Amir|Eitan|E|', 'Abdul Razak|Albiruni R|AR|']
D018943:Anthracyclines D000971:Antineoplastic Combined Chemotherapy Protocols D018572:Disease-Free Survival D004317:Doxorubicin D006801:Humans D016032:Randomized Controlled Trials as Topic D012509:Sarcoma
Chemotherapy Soft tissue sarcoma Sarcoma