Role of gemcitabine-based combination therapy in the management of advanced pancreatic cancer: A systematic review and meta-analysis of randomized trials
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E-Artikel
Titel:
Role of gemcitabine-based combination therapy in the management of advanced pancreatic cancer: A systematic review and meta-analysis of randomized trials
Beschreibung:
e14577 Background: Pancreatic cancer is the 4th leading cause of cancer-related death worldwide. Single-agent chemotherapy with gemcitabine represents a cornerstone for advanced disease treatment. To date, almost all trials, designed to evaluate the benefit of the addition of a second agent to gemcitabine, failed to demonstrate an improvement in overall survival (OS). We performed a systematic review and a meta-analysis of randomized clinical trials to assess the efficacy and safety of gemcitabine-based combination regimens versus gemcitabine alone in the management of pancreatic cancer. Methods: Clinical trials were selected by searching Medline database and abstracts from major cancer meetings. We considered the Jan 1997 - Jan 2012 time frame. Primary end-point was OS, secondary end-points were response rate (RR), disease control rate (DCR) and safety. Hazard ratios (HRs) of OS, odds-ratios (ORs) of RR, DCR and risk ratios of grade 3-4 toxicity rates, were extracted as presented in retrieved studies and used for statistical analysis. Meta-analytic estimates were derived using random-effects model. Results: Thirty-three trials for a total of 10371 patients were selected and included in the final analysis. The analysis showed for combination chemotherapy a benefit in terms of OS (HR: 0.92; 95%CI: 0.88-0.96; p < 0.001). OR of both RR and DCR demonstrated a significant advantage for combination therapy (OR for RR: 0.63, 95%CI: 0.50-0.80, p=0.006; OR for DCR: 0.78; 95%CI: 0.64-0.94; p=0.002). Toxicities were more frequent in the combination treatment group and a significant value in term of risk ratio was reached for diarrhea (0.53, 95%CI: 0.36-0.79), nausea (0.74, 95%CI: 0.56-0.96), neutropenia (0.74, 95%CI: 0.62-0.89) and thrombocytopenia (0.59, 95%CI: 0.44-0.79). Conclusions: Combinationchemotherapy compared to gemcitabine alone significantly improves OS. However, this advantage seems to be marginal and at the cost of increased toxicity, suggesting the use of gemcitabine-based combination regimens only in selected patients. New approaches based on preclinical findings, in the era of targeted therapy, are eagerly awaited on this specific topic.