title: Combination of cisplatin/S-1 in the treatment of patients with advanced gastric or gastroesophageal adenocarcinoma: Results of noninferiority and safety analyses compared with cisplatin/5-fluorouracil in the First-Line Advanced Gastric Cancer Study.
abstract: BACKGROUND
  The aim of developing oral fluorouracil (5-FU) is to provide a more convenient administration route with similar efficacy and the best achievable tolerance. S-1, a novel oral fluoropyrimidine, was specifically designed to overcome the limitations of intravenous fluoropyrimidine therapies.
  
  
  METHODS
  A multicentre, randomised phase 3 trial was undertaken to compare S-1/cisplatin (CS) with infusional 5-FU/cisplatin (CF) in 1053 patients with untreated, advanced gastric/gastroesophageal adenocarcinoma. This report discusses a post-hoc noninferiority overall survival (OS) and safety analyses.
  
  
  RESULTS
  Results (1029 treated; CS = 521/CF = 508) revealed OS in CS (8.6 months) was statistically noninferior to CF (7.9 months) [hazard ratio (HR) = 0.92 (two-sided 95% confidence interval (CI), 0.80-1.05)] for any margin equal to or greater than 1.05. Statistically significant safety advantages for the CS arm were observed [G3/4 neutropenia (CS, 18.6%; CF, 40.0%), febrile neutropenia (CS, 1.7%; CF, 6.9%), G3/4 stomatitis (CS, 1.3%; CF, 13.6%), diarrhoea (all grades: CS, 29.2%; CF, 38.4%) and renal adverse events (all grades: CS, 18.8%; CF, 33.5%)]. Hand-foot syndrome, infrequently reported, was mainly grade 1/2 in both arms. Treatment-related deaths were significantly lower in the CS arm than the CF arm (2.5% and 4.9%, respectively; P<0.047).
  
  
  CONCLUSIONS
  CS is noninferior to CF with a better safety profile and provides a new treatment option for patients with advanced gastric carcinoma.
authors.affiliation: Department of Gastrointestinal Medical Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, USA. Electronic address: jajani@mdanderson.org.
authors.forename: J A
authors.initials: JA
authors.lastname: Ajani
authors.forename: M
authors.initials: M
authors.lastname: Buyse
authors.forename: M
authors.initials: M
authors.lastname: Lichinitser
authors.forename: V
authors.initials: V
authors.lastname: Gorbunova
authors.forename: G
authors.initials: G
authors.lastname: Bodoky
authors.forename: J Y
authors.initials: JY
authors.lastname: Douillard
authors.forename: S
authors.initials: S
authors.lastname: Cascinu
authors.forename: V
authors.initials: V
authors.lastname: Heinemann
authors.forename: R
authors.initials: R
authors.lastname: Zaucha
authors.forename: A
authors.initials: A
authors.lastname: Carrato
authors.forename: D
authors.initials: D
authors.lastname: Ferry
authors.forename: V
authors.initials: V
authors.lastname: Moiseyenko
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000453:epidemiology / Q000401:mortality; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage* / Q000009:adverse effects; D018450:Disease Progression; D004338:Drug Combinations; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000453:epidemiology / Q000401:mortality; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D010094:Oxonic Acid / Q000008:administration & dosage* / Q000009:adverse effects; D013274:Stomach Neoplasms / Q000188:drug therapy*; D005641:Tegafur / Q000008:administration & dosage* / Q000009:adverse effects; D055815:Young Adult
chemical_list: D004338:Drug Combinations; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D002945:Cisplatin; D005472:Fluorouracil
keywords: 5-Fluorouracil; Cisplatin; FLAGS; Gastric; Phase 3; S-1