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

Chao Tu,Yuan-Yuan Li,Jin-Yu Wang,Feng Zheng,Ke-Qing Qian

doi:10.7314/apjcp.2015.16.14.5681

Abstract

Pancreatic cancer ranks fourth in deaths caused by cancers throughout the world. Gemcitabine chemotherapy is the primary method of treatment of advanced pancreatic cancer, and in asco2014, it is still first- line chemotherapy. However 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 review and a meta-analysis of randomized controlled trials (RCTs) to assess whether gemcitabine+fluoropyrimidine combination therapy improves the prognosis of unresectable pancreatic cancer compared with gemcitabine treatment alone. A quantitative up-to-date meta-analysis was undertaken to investigate the efficacy of gemcitabine-based combination treatment compared with gemcitabine monotherapy for locally advanced or metastatic pancreatic cancer. Inclusion was limited to high-quality randomized clinical trials. 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 the primary endpoint of overall survival (OS), gemcitabine-based combination therapy demonstrated significantly better outcome (HR, 0.88; 95% CI, 0.81-0.95) than gemcitabine monotherapy. The analysis of progression free survival (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 found that 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). Gemcitabine combination therapy provides a modest improvement of survival, but is associated with more toxicity compared with gemcitabine monotherapy.

Highlights

Pancreatic cancer is the fourth leading cause of cancer death in the US and it remains a highly lethal malignancy despite advances in treatment
With subgroup analysis according to the method of dosing delivery, we found that 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)
145 Potentially relevant studies were included from search of COCHRANE CENTRAL REGISTER OF CONTROLLED TRIALS, PUBMED, EMBASE and WEB OF SCIENCE, 7 Studies identified were selected by hand search of references, after exclusion on basis of title and abstract which were unrelated to our study design, we chose to read 31 full text of articles, and identified 12 studies in our meta-analysis

Summary

Introduction

Pancreatic cancer is the fourth leading cause of cancer death in the US and it remains a highly lethal malignancy despite advances in treatment (el-Kamar et al, 2003; Bond-Smith et al, 2012). Gemcitabine has represented the reference standard for the treatment of advanced pancreatic cancer (APC) since 1996, based on improvements in overall survival (OS) and clinical benefit response (Burris et al, 1997). We performed a systematic review and a meta-analysis of randomized controlled trials (RCTs) to assess whether gemcitabine+fluoropyrimidine combination therapy improves the prognosis of unresectable pancreatic cancer compared with gemcitabine treatment alone. Materials and Methods: A quantitative up-to-date meta-analysis was undertaken to investigate the efficacy of gemcitabine-based combination treatment compared with gemcitabine monotherapy for locally advanced or metastatic pancreatic cancer. The analysis of progression free survival (PFS) 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). Conclusions: Gemcitabine combination therapy provides a modest improvement of survival, but is associated with more toxicity compared with gemcitabine monotherapy

Methods

Results

Conclusion