title: Weekly infusional high-dose fluorouracil (HD-FU), HD-FU plus folinic acid (HD-FU/FA), or HD-FU/FA plus biweekly cisplatin in advanced gastric cancer: randomized phase II trial 40953 of the European Organisation for Research and Treatment of Cancer Gastrointestinal Group and the Arbeitsgemeinschaft Internistische Onkologie.
abstract: OBJECTIVE
  This multicentric, randomized, two-stage phase II trial evaluated three simplified weekly infusional regimens of fluorouracil (FU) or FU plus folinic acid (FA) and cisplatin (Cis) with the aim to select a regimen for future phase III trials.
  
  
  METHODS
  A total of 145 patients with advanced gastric cancer where randomly assigned to weekly FU 3,000 mg/m2/24 hours (HD-FU), FU 2,600 mg/m2/24 hours plus dl-FA 500 mg/m2 or l-FA 250 mg/m2 (HD-FU/FA), or FU 2000 mg/m2/24 hours plus FA plus biweekly Cis 50 mg/m2, each administered for 6 weeks with a 1-week rest. The primary end point was the response rate.
  
  
  RESULTS
  Confirmed responses were observed in 6.1% (two of 33) of the eligible patients treated with HD-FU, in 25% (12 of 48, including one complete remission [CR]) with HD-FU/FA, and in 45.7% (21 of 46, including four CRs) with HD-FU/FA/Cis. The HD-FU arm was closed after stage 1 because the required minimum number of responses was not met. The median progression-free survival of all patients in the HD-FU, HD-FU/FA, and HD-FU/FA/Cis arm was 1.9, 4.0, and 6.1 months, respectively. The median overall survival was 7.1, 8.9, and 9.7 months, and the survival rate at 1 year was 24.3%, 30.3%, and 45.3%, respectively. Grade 4 toxicities were rare. The most relevant grade 3/4 toxicities were neutropenia in 1.9%, 5.4%, and 19.6%, and diarrhea in 2.7%, 1.9%, and 3.9% of the cycles in the HD-FU, HD-FU/FA, and HD-/FU/Cis arms, respectively.
  
  
  CONCLUSIONS
  Weekly infusional FU/FA plus biweekly Cis is effective and safe in patients with gastric cancer.
authors.affiliation: Caritasklinik St Theresia, Saarbrücken, Germany. m.lutz@caritasklinik.de
authors.forename: Manfred P
authors.initials: MP
authors.lastname: Lutz
authors.forename: Hansjochen
authors.initials: H
authors.lastname: Wilke
authors.forename: D J Theo
authors.initials: DJ
authors.lastname: Wagener
authors.forename: Udo
authors.initials: U
authors.lastname: Vanhoefer
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Jeziorski
authors.forename: Susanna
authors.initials: S
authors.lastname: Hegewisch-Becker
authors.forename: Leopold
authors.initials: L
authors.lastname: Balleisen
authors.forename: Eric
authors.initials: E
authors.lastname: Joossens
authors.forename: Rob L
authors.initials: RL
authors.lastname: Jansen
authors.forename: Muriel
authors.initials: M
authors.lastname: Debois
authors.forename: Ullrich
authors.initials: U
authors.lastname: Bethe
authors.forename: Michel
authors.initials: M
authors.lastname: Praet
authors.forename: Jacques
authors.initials: J
authors.lastname: Wils
authors.forename: Eric
authors.initials: E
authors.lastname: Van Cutsem
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage; D005060:Europe; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D007262:Infusions, Intravenous; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D013274:Stomach Neoplasms / Q000188:drug therapy*; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D002945:Cisplatin; D002955:Leucovorin; D005472:Fluorouracil