Multicenter Phase III Comparison of Cisplatin/S-1 With Cisplatin/Infusional Fluorouracil in Advanced Gastric or Gastroesophageal Adenocarcinoma Study: The FLAGS Trial

• Published in: Journal of clinical oncology Vol. 28; no. 9; pp. 1547 - 1553
• Main Authors: AJANI, Jaffer A, RODRIGUEZ, Wuilbert, BODOKY, Gyorgy, MOISEYENKO, Vladimir, LICHINITSER, Mikhail, GORBUNOVA, Vera, VYNNYCHENKO, Ihor, GARIN, August, LANG, Istvan, FALCON, Silvia
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Society of Clinical Oncology 20.03.2010
• Subjects: Adenocarcinoma - drug therapy; Adenocarcinoma - secondary; Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols - administration & dosage; Cisplatin - administration & dosage; Drug Combinations; Esophageal Neoplasms - drug therapy; Esophageal Neoplasms - secondary; Female; Fluorouracil - administration & dosage; Humans; Male; Middle Aged; Oxonic Acid - administration & dosage; Stomach Neoplasms - drug therapy; Stomach Neoplasms - secondary; Survival Analysis; Tegafur - administration & dosage; Treatment Outcome; Young Adult
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/JCO.2009.25.4706

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. 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/m(2) divided in two daily doses for 21 days and cisplatin at 75 mg/m(2) intravenously on day 1, repeated every 28 days (527 patients) or infusional fluorouracil at 1,000 mg/m(2)/24 hours for 120 hours and cisplatin at 100 mg/m(2) intravenously 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. 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). 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.