Medicine
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SYSTEMATIC REVIEW
AND
META-ANALYSIS
Gemcitabine Compared With Gemcitabine and S-1 Combination Therapy in Advanced Pancreatic Cancer A Systematic Review and Meta-Analysis Doudou Li, MD, Changhao Chen, MD, Yu Zhou, PhD, Rufu Chen, PhD, Xinxiang Fan, PhD, Zhuofei Bi, MD, Zhihua Li, MD, and Yimin Liu, MD
Abstract: Several reports suggest that gemcitabine (GEM) plus S-1 combination (GS) is associated to prolong the survival in patients with unresectable pancreatic cancer (PC). We conducted a systemic review and meta-analysis of studies comparing the safety and efficacy of GS versus GEM. Summary data from randomized trials and retrospective studies were searched in PubMed, EMBASE, Web of Science, and the Cochrane Library. Statistical analyses were conducted to calculate the hazard ratios (HRs) and relative risk (RR) with 95% confidence intervals (CIs) using random-effects models. Subgroup analyses based on the chemotherapy cycles were performed to explore the efficacy and toxicity for therapy. Sensitivity analyses were conducted by removing specific studies to assess the effects of study quality. Between January 2004 and August 2012, 4 RCTs and 2 retrospective studies including a total of 1025 cases were identified. The overall survival (OS) (HR: 0.82; 95% CI, 0.70–0.96; P ¼ 0.01) and progression-free survival (PFS) (HR: 0.65; 95% CI, 0.55–0.77; P < 0.001) for the GS arm were significantly longer than the GEM arm. The differences in objective response rate (ORR) (RR: 1.24; 95% CI, 1.17–1.33; P < 0.001) and disease control rate (DCR) were also better in the GS arm (RR: 1.37; 95% CI, 1.19–1.59; P < 0.001). Grades 3 to 4 toxicities in both the groups were similar except neutropenia and diarrhea, which were more frequent in the GS arm (P < 0.001). In the subgroup analysis, the cycle for chemotherapy every 4 weeks has equivalent efficacy and less toxicity than regimens every 3 weeks in the GS arm. The current meta-analysis suggested that GEM significantly prolonged OS and PFS when added to S-1 combination in patients with
Editor: Holger Cramer. Received: January 17, 2015; revised: July 1, 2015; accepted: July 17, 2015. From the Department of Oncology (DL, ZB, ZL, YL); Department of Urology (CC, XF); Department of Hepatobiliary Surgery (RC), Sun Yatsen Memorial Hospital; and Department of General Surgery (YZ), Guangdong General Hospital, Guangzhou, China. Correspondence: Yimin Liu, Department of Oncology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, 107 Yan-Jiang Xi Road, GuangZhou 510120, China (e-mail:
[email protected]). Supplemental Digital Content is available for this article. DL, CC, and YZ contributed equally to this study. Author contributions: Conception and design—YL, DL, and CC; Administrative support—DL, CC, RC, ZB, YL, and ZL; Provision of study materials or patients—YZ and XF; Collection and assembly of data: CC, YZ, and XF; Data analysis and interpretation—DL, CC, RC, ZB, YZ, XF, and YL; Manuscript writing—all authors; Final approval of manuscript—all authors. This study was not supported by any pharmaceutical company or grants; the cost was borne by the authors’ institutions. All authors approved the report. The authors have no conflicts of interest to disclose. Copyright # 2015 Wolters Kluwer Health, Inc. All rights reserved. This is an open access article distributed under the Creative Commons Attribution- NonCommercial License, where it is permissible to download, share and reproduce the work in any medium, provided it is properly cited. The work cannot be used commercially. ISSN: 0025-7974 DOI: 10.1097/MD.0000000000001345
Medicine
Volume 94, Number 35, September 2015
unresectable PC. GS therapy also offers better ORR and DCR than GEM monotherapy and no unexpected toxicity was evident. (Medicine 94(35):e1345) Abbreviations: BSA = body surface area, CIs = confidence intervals, CR = complete response, DCR = disease control rate, GEM = gemcitabine, GS = gemcitabine and S-1, HRs = hazard ratios, ORR = objective response rate, OS = overall survival, PC = pancreatic carcinoma, PFS = progression-free survival, PR = partial response, RR = relative risk.
INTRODUCTION
P
ancreatic cancer (PC) is one of the most lethal digestive system tumor with a 5-year survival rate of
