An Updated Meta-analysis and System Review:is emcitabine+Fluoropyrimidine in Combination a Better herapy Versus Gemcitabine Alone for Advanced and Unresectable Pancreatic Cancer?


Background: Pancreatic cancer ranks fourth in deaths caused by cancers throughout the world. Gemcitabinechemotherapy is the primary method of treatment of advanced pancreatic cancer, and in asco2014, it is still firstlinechemotherapy. Howeve,r gemcitabine+fluorouracil regimens are also licensed and widely used worldwide.Clinical trials are the best way to evaluate drug efficacy. In this study, we performed a systematic reviewand a meta-analysis of randomized controlled trials (RCTs) to assess whether gemcitabine+fluoropyrimidinecombination therapy improves the prognosis of unresectable pancreatic cancer compared with gemcitabinetreatment alone. Materials and
Methods: A quantitative up-to-date meta-analysis was undertaken to investigatethe efficacy of gemcitabine-based combination treatment compared with gemcitabine monotherapy for locallyadvanced or metastatic pancreatic cancer. Inclusion was limited to high-quality randomized clinical trials.
Results: A total of 12 studies were included in the present analysis, with a total of 3,038 patients recruited.The studies were divided into three subgroups including 5-FU / CAP / S-1 combined with gemcitabine. For theprimary endpoint of overall survival (OS), gemcitabine-based combination therapy demonstrated significantlybetter outcome (HR, 0.88; 95% CI, 0.81-0.95) than gemcitabine monotherapy. The analysis of progression freesurvival (PFS) also provided a significant result for the combined therapy in a total of 8 trials (2,130 patients)(HR, 0.74; 95% CI, 0.63-0.86). With subgroup analysis according to the method of dosing delivery, we foundthat in the injection group with 3 trials (889 patients), a negative result was found (HR, 0.93; 95% CI, 0.77-1.12);while a positive result was observed in the oral group with 9 trials (2,149 patients) (HR, 0.87; 95% CI, 0.80-0.95).
Conclusions: Gemcitabine combination therapy provides a modest improvement of survival, but is associatedwith more toxicity compared with gemcitabine monotherapy.