Gemcitabine-based Cytotoxic Doublets Chemotherapy for Advanced Pancreatic Cancer: Updated Subgroup Meta-analyses of Overall Survival

• Published in: Japanese journal of clinical oncology Vol. 40; no. 5; pp. 432 - 441
• Main Authors: Xie, De-rong, Yang, Qiong, Chen, Deng-lin, Jiang, Zhi-min, Bi, Zhuo-fei, Ma, Wen, Zhang, Yuan-dong
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01.05.2010
• Subjects: Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Capecitabine; Deoxycytidine - administration & dosage; Deoxycytidine - analogs & derivatives; Fluorouracil - administration & dosage; Fluorouracil - analogs & derivatives; gemcitabine; Humans; meta-analysis; Odds Ratio; Organoplatinum Compounds - administration & dosage; oxaliplatin; pancreatic neoplasms; Pancreatic Neoplasms - drug therapy; Randomized Controlled Trials as Topic; Survival Analysis
• ISSN: 0368-2811; 1465-3621
• DOI: 10.1093/jjco/hyp198

Objective Previous meta-analyses showed a survival advantage with gemcitabine (GEM)-based combinations over GEM in advanced pancreatic cancer. Therefore, it would be valuable to explore the specific active regimens based on a subgroup meta-analysis. Methods Updated data by comprehensive search of the literature from databases and conference proceedings. Subgroup meta-analysis compared GEM with GEM-based doublets chemotherapy in terms of 6-month overall survival (OS) and 1-year OS. Results Eighteen randomized controlled trials with 4237 patients were included, which were divided into five subgroups: GEM/capecitabine, GEM/cisplatin, GEM/5-fluorouracil, GEM/irinotecan and GEM/oxaliplatin. In each subgroup, risk ratios (RRs) for 6-month OS were 0.85 (P = 0.04), 0.99 (P = 0.88), 0.95 (P = 0.46), 1.03 (P = 0.77) and 0.80 (P = 0.001), respectively, and RRs for 1-year OS were 0.94 (P = 0.14), 0.99 (P = 0.75), 0.96 (P = 0.19), 1.00 (P = 0.97) and 0.93 (P = 0.05), respectively. A meta-analysis of the trials with adequate information on performance status (PS) was performed in four trials with 1325 patients. Patients with a good PS did not show a survival benefit when receiving combination chemotherapy. RRs for 6-month and 1-year OS were 0.82 (P = 0.18) and 0.93 (P = 0.08). In contrast, application of combination chemotherapy to patients with a poor PS appeared to be harmful. RRs were 1.17 (P = 0.04) for 6-month OS and 1.09 (P = 0.04) for 1-year OS. Conclusions The meta-analysis indicated a significant survival benefit when GEM was either combined with capcitabine or oxaliplatin. On the basis of a preliminary subgroup analysis, pancreatic cancer patients with a poor PS appeared to have a worse survival benefit from GEM-based cytotoxic doublets.