title: Gemcitabine plus S-1: a hopeful frontline treatment for Asian patients with unresectable advanced pancreatic cancer.
abstract: OBJECTIVE
  Gemcitabine-based chemotherapy is widely used for unresectable advanced pancreatic cancer which contains locally advanced and metastatic pancreatic cancer. We performed meta-analysis to examine whether gemcitabine plus S-1 could improve treatment efficacy as first-line chemotherapy for those patients when compared with gemcitabine alone.
  
  
  METHODS
  STATA was used to estimate the summary hazard ratios or odds ratios and their 95% confidence intervals. Heterogeneity among trials was examined by Cochran's χ(2) test. Publication bias was evaluated by Begg's and Egger's tests. Subgroup analysis based on the extent of disease was performed.
  
  
  RESULTS
  Four randomized controlled trials including 878 Asian patients were analyzed. In total meta-analysis, gemcitabine plus S-1 significantly improved overall survival (hazard ratio, 0.82; 95% confidence interval, 0.70-0.96; P = 0.015), progression-free survival (hazard ratio, 0.64; 95% confidence interval, 0.55-0.74; P < 0.001), overall response rate (odds ratio, 3.00; 95% confidence interval, 2.04-4.41; P < 0.001) and disease control rate (odds ratio, 1.78; 95% confidence interval, 1.32 to 2.39; P < 0.001), and was associated with more but manageable hematologic (leukocytopenia, neutropenia, thrombocytopenia) and non-hematologic (diarrhea, stomatitis, nausea, rash) adverse events. In subgroup analysis, gemcitabine plus S-1, comparing with gemcitabine, significantly improved overall survival in locally advanced patients (hazard ratio, 0.69; 95% confidence interval, 0.48 to 0.99; P = 0.022) but not in metastatic patients (hazard ratio, 0.75; 95% confidence interval, 0.46-1.23; P = 0.256).
  
  
  CONCLUSIONS
  This meta-analysis confirmed the survival benefits of gemcitabine plus S-1 as first-line treatment for unresectable advanced pancreatic cancer at least in Asia, while good Eastern Cooperative Oncology group performance status was warranted. Importantly, we highlighted the significant overall survival benefit of gemcitabine plus S-1 in locally advanced patients but not in metastatic patients.
authors.affiliation: Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing Department of Radiation Oncology, The First Affiliated Hospital of Soochow University, Soochow University, Suzhou.
authors.forename: Chunxiang
authors.initials: C
authors.lastname: Cao
authors.affiliation: Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing.
authors.forename: Meng
authors.initials: M
authors.lastname: Kuang
authors.affiliation: Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing.
authors.forename: Wei
authors.initials: W
authors.lastname: Xu
authors.affiliation: Department of Oncology, Nantong Tumor Hospital, Nantong.
authors.forename: Xunlei
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing tangcuiju2013@163.com jinfeichen@sohu.com.
authors.forename: Jinfei
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing tangcuiju2013@163.com jinfeichen@sohu.com.
authors.forename: Cuiju
authors.initials: C
authors.lastname: Tang
mesh_terms: D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000009:adverse effects*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D044466:Asian People; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D004338:Drug Combinations; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000188:drug therapy / Q000556:secondary; D008175:Lung Neoplasms / Q000188:drug therapy / Q000556:secondary; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010094:Oxonic Acid / Q000008:administration & dosage / Q000009:adverse effects; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D010534:Peritoneal Neoplasms / Q000188:drug therapy / Q000556:secondary; D016032:Randomized Controlled Trials as Topic; D058028:Research Report / Q000592:standards; D005641:Tegafur / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D004338:Drug Combinations; D003841:Deoxycytidine; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D000093542:Gemcitabine
keywords: S-1; chemotherapy; gemcitabine; meta-analysis; pancreatic cancer