title: The efficacy and safety of S-1-based regimens in the first-line treatment of advanced gastric cancer: a systematic review and meta-analysis.
abstract: BACKGROUND
  S-1 is first-line therapy for advanced gastric cancer in Asia and is used with increased frequency in Western counties. We conducted a meta-analysis to investigate the efficacy and toxicity of S-1-based therapy compared with 5-fluorouracil (5-FU)/capecitabine-based therapy and S-1-based combination therapy compared with S-1 monotherapy.
  
  
  METHODS
  MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, American Society of Clinical Oncology meeting abstracts, European Society for Medical Oncology meeting abstracts and ClinicalTrials.gov were searched for randomized clinical trials until May 2015. Data were extracted for overall survival (OS), progression-free-survival (PFS), objective response rate (ORR) and grade 1-2 and grade 3-4 adverse events. Stratified OS data for subgroups were extracted.
  
  
  RESULTS
  S-1 was not different from 5-FU (eight studies, n = 2788) in terms of OS [hazard ratio (HR) 0.93, 95 % confidence interval (CI) 0.85-1.01] and PFS (HR 0.87, 95 % CI 0.73-1.04), whereas ORR was higher (risk ratio 1.43, 95 % CI 1.05-1.96). There was no subgroup difference in efficacy among Asian and Western patients, but in Western patients S-1 was associated with a lower rate of febrile neutropenia, toxicity-related deaths and grade 3-4 stomatitis and mucositis compared with 5-FU. S-1 showed no difference in efficacy compared with capecitabine (three studies, n = 329), but was associated with a lower rate of grade 3-4 neutropenia and grade 1-2 hand-foot syndrome. S-1-combination therapy was superior to S-1 monotherapy (eight studies, n = 1808) in terms of OS (HR 0.76, 95 % CI 0.65-0.90), PFS (HR 0.68, 95 % CI 0.56-0.82) and ORR (risk ratio 1.20, 95 % CI 1.04-1.38) but was more toxic. Survival benefit of S-1 combination therapy over S-1 monotherapy was most pronounced in patients with non-measurable disease, diffuse-type histological features and peritoneal metastasis.
  
  
  CONCLUSIONS
  S-1 is effective and tolerable as first-line therapy for advanced gastric cancer in both Asian and Western countries.
authors.affiliation: Department of Medical Oncology, Academic Medical Centre, University of Amsterdam, Meibergdreef 9, F4-224, 1105 AZ, Amsterdam, The Netherlands.
authors.forename: Emil
authors.initials: E
authors.lastname: Ter Veer
authors.affiliation: Department of Medical Oncology, Academic Medical Centre, University of Amsterdam, Meibergdreef 9, F4-224, 1105 AZ, Amsterdam, The Netherlands.
authors.forename: Nadia Haj
authors.initials: NH
authors.lastname: Mohammad
authors.affiliation: Department of Psychology, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Paul
authors.initials: P
authors.lastname: Lodder
authors.affiliation: Department of Medical Oncology, Academic Medical Centre, University of Amsterdam, Meibergdreef 9, F4-224, 1105 AZ, Amsterdam, The Netherlands.
authors.forename: Lok Lam
authors.initials: LL
authors.lastname: Ngai
authors.affiliation: Department of Medical Oncology, Academic Medical Centre, University of Amsterdam, Meibergdreef 9, F4-224, 1105 AZ, Amsterdam, The Netherlands.
authors.forename: Mary
authors.initials: M
authors.lastname: Samaan
authors.affiliation: Department of Medical Oncology, Academic Medical Centre, University of Amsterdam, Meibergdreef 9, F4-224, 1105 AZ, Amsterdam, The Netherlands.
authors.forename: Martijn G H
authors.initials: MG
authors.lastname: van Oijen
authors.affiliation: Department of Medical Oncology, Academic Medical Centre, University of Amsterdam, Meibergdreef 9, F4-224, 1105 AZ, Amsterdam, The Netherlands. h.vanlaarhoven@amc.uva.nl.
authors.forename: Hanneke W M
authors.initials: HW
authors.lastname: van Laarhoven
mesh_terms: D004338:Drug Combinations; D006801:Humans; D010094:Oxonic Acid / Q000627:therapeutic use*; D012449:Safety; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology; D005641:Tegafur / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D004338:Drug Combinations; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid
keywords: Advanced gastric cancer; Chemotherapy; Meta-analysis; S-1