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


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/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.


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).


CONCLUSIONS
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.
Department of Gastrointestinal Medical Oncology, The University of Texas M. D. Anderson Cancer Center, TX 77030, USA. jajani@mdanderson.org
Jaffer A
JA
Ajani
Wuilbert
W
Rodriguez
Gyorgy
G
Bodoky
Vladimir
V
Moiseyenko
Mikhail
M
Lichinitser
Vera
V
Gorbunova
Ihor
I
Vynnychenko
August
A
Garin
Istvan
I
Lang
Silvia
S
Falcon
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000556:secondary; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D002945:Cisplatin / Q000008:administration & dosage; D004338:Drug Combinations; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000556:secondary; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D008297:Male; D008875:Middle Aged; D010094:Oxonic Acid / Q000008:administration & dosage; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000556:secondary; D016019:Survival Analysis; D005641:Tegafur / Q000008:administration & dosage; D016896:Treatment Outcome; D055815:Young Adult
D004338:Drug Combinations; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D002945:Cisplatin; D005472:Fluorouracil