Multicenter phase III comparison of cisplatin/S-1 with cisplatin/infusional fluorouracil in advanced gastric or gastroesophageal adenocarcinoma study: The FLAGS trial

Jaffer A. Ajani, Wuilbert Rodriguez, Gyorgy Bodoky, Vladimir Moiseyenko, Mikhail Lichinitser, Vera Gorbunova, Ihor Vynnychenko, August Garin, Istvan Lang, Silvia Falcon

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Abstract

Purpose: Patients with advanced gastric or gastroesophageal adenocarcinoma need more efficacious and safer treatments than established today. S-1, a contemporary oral fluoropyrimidine, can provide that advantage. Patients and Methods: This study was conducted in 24 countries and 146 centers. One thousand fifty-three patients were stratified (center, number of metastatic sites, prior adjuvant therapy, and measurable cancer) and randomly assigned. Patients received either S-1 at 50 mg/m2divided in two daily doses for 21 days and cisplatin at 75 mg/m2intravenously on day 1, repeated every 28 days (527 patients) or infusional fluorouracil at 1,000 mg/m2/24 hours for 120 hours and cisplatin at 100 mg/m2intravenously on day 1, repeated every 28 days (526 patients). The primary end point was superiority in overall survival (OS) from cisplatin/S-1 compared with cisplatin/infusional fluorouracil in patients with advanced, untreated gastric, or gastroesophageal adenocarcinoma. The secondary end points were response rate, progression-free survival, time to treatment failure, and safety. Results: The median OS was 8.6 months in the cisplatin/S-1 arm and 7.9 months in the cisplatin/infusional fluorouracil arm (HR, 0.92; 95% CI, 0.80 to 1.05; P = .20). Significant safety advantages were observed in the cisplatin/S-1 arm compared with the cisplatin/infusional fluorouracil arm for the rates of grade 3/4 neutropenia (32.3% v 63.6%), complicated neutropenia (5.0% v 14.4%), stomatitis (1.3% v 13.6%), hypokalemia (3.6% v 10.8%), and treatment-related deaths (2.5% v 4.9%; P < .05). Conclusion: Cisplatin/S-1 did not prolong OS of patients with advanced gastric or gastroesophageal adenocarcinoma compared with cisplatin/infusional fluorouracil, but it did result in a significantly improved safety profile.

Original languageEnglish
Pages (from-to)1547-1553
Number of pages7
JournalJournal of Clinical Oncology
Volume28
Issue number9
DOIs
Publication statusPublished - Mar 20 2010

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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