Extended safety and efficacy data on S-1 plus cisplatin in patients with untreated, advanced gastric carcinoma in a multicenter phase II study

BACKGROUND. S-1 is a promising oral fluoropyrimidine. The authors obtained extended Phase II safety and efficacy data in a multicenter setting for the S-1 plus cisplatin combination: The experimental arm of the global Phase III First-Line Advanced Gastric Cancer Study (FLAGS) is being compared with 5-fluorouracil/cisplatin. METHODS. Eligible patients had untreated, histologically confirmed advanced gastric cancer (AGC), a Karnofsky performance status (KPS) ≥70%, adequate organ function, and provided written consent. Patients received S-1 (25 mg/m² twice daily on Days 1 through 21) plus cisplatin (75 mg/m² on Day 1) every 28 days. The confirmed overall response rate (CORR) also was designated by an external review. The time to progression (TTP), median survival (MS), and safety were assessed. RESULTS. All 72 patients were assessed for safety and survival, and 64 patients were assessed for CORR. The median KPS was 90%. The median number of treatment cycles was 4. The CORR was 55% (95% confidence interval [95% CI], 42-67%). The median duration of response was >5 months. At 6 months, only an estimated 38% of patients had cancer progression. The estimated MS was 10.4 months (95% CI, 8.6-12.9 months). At least 1 serious adverse event occurred in 44% of patients. The frequent grade 3 or 4 toxicities (using the National Cancer Institute Common Toxicity Criteria), which occurred in >10% of patients, included fatigue/asthenia (24%), emesis (17%), nausea (15%), diarrhea (13%), and neutropenia (19%). Complicated neutropenia (1.4%) and grade 4 diarrhea (1.4%) were rare. CONCLUSIONS. The current extended data confirmed that S-1 combined with cisplatin had a highly desirable safety profile. The efficacy against AGC, according to an external review, was encouraging. FLAGS is expected to complete its accrual of 1050 patients by December 2006.