title: Safety of cisplatin combined with continuous 5-FU versus bolus 5-FU and leucovorin, in metastatic gastrointestinal cancer (FFCD 9404 randomised trial).
abstract: BACKGROUND
  The objective of this phase III study was to compare the safety and efficacy of FLP (modulation of 5-FU (Fluorouracil) by folinic acid or leucovorin (LV) and cisplatin vs. FP (5-FU combined with Cisplatin) as a first line chemotherapy in advanced oesophageal, gastric and pancreatic cancer.
  
  
  METHODS
  232 patients with measurable lesions were randomised to receive at the first cycle either FP (arm A: 5-FU 800 mg/m2/d in continuous infusion 5 days and cisplatin 100 mg/m2 on day 1 or 2), or FLP (arm B: LV, 100 mg/m2/d in bolus 5 days, followed by 5-FU 350 mg/m2/d in 1 h infusion 5 days and cisplatin 100 mg/m2 on day 1 or 2). In case of no grade 3-4 haematological and diarrhoea toxicity, the dose of 5-FU was increased to 1000 mg/m2/d and 400 mg/m2/d in the two arms respectively, for the subsequent cycles until disease progression.
  
  
  RESULTS
  The distribution of primary tumours was: 19 squamous cell carcinoma of the oesophagus, 19 oesophageal adenocarcinoma, 91 gastric and 97 pancreatic adenocarcinoma. Safety remained acceptable and comparable in the two arms except for the severe grade 3-4 mucositis, which was lower in arm B (4.5 vs. 16.4%, p < 0.009). Efficacy in terms of tumour response and survival was similar in the two arms, showing an objective response rate (after external review) of 18.6% (95% confidence interval (CI) 11.4-25.8%) in arm A vs. 15% (95% CI 8.5-21.6%) in arm B, an overall median survival of 24 weeks in arm A vs. 24.7 in arm B (p = 0.83) and a progression-free median survival of 12.4 weeks vs. 12.1 in arms A and B, respectively (p = 0.91).
  
  
  CONCLUSIONS
  The FLP regimen is substantially equivalent to FP in terms of safety and quality of life, as well as for antitumour efficacy in these carcinomas; the only slight advantage of FLP in this study concerns mucositis. Based on these results, FLP could be used as an alternative to FP when appropriate.
authors.affiliation: CRLC Val d'Aurelle-Paul Lamarque, 34298 Montpellier, France. jduffour@valdorel.fnclcc.fr
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Duffour
authors.forename: Olivier
authors.initials: O
authors.lastname: Bouché
authors.forename: Philippe
authors.initials: P
authors.lastname: Rougier
authors.forename: Chantal
authors.initials: C
authors.lastname: Milan
authors.forename: Laurent
authors.initials: L
authors.lastname: Bedenne
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Seitz
authors.forename: Bruno
authors.initials: B
authors.lastname: Buecher
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Legoux
authors.forename: Michel
authors.initials: M
authors.lastname: Ducreux
authors.forename: Denis
authors.initials: D
authors.lastname: Vetter
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Raoul
authors.forename: Eric
authors.initials: E
authors.lastname: François
authors.forename: Marc
authors.initials: M
authors.lastname: Ychou
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005770:Gastrointestinal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D016019:Survival Analysis
chemical_list: D002945:Cisplatin; D005472:Fluorouracil