Randomized phase II study of daily and alternate-day administration of S-1 for advanced gastric cancer (JFMC43-1003)

PURPOSE: Although S-1 based chemotherapy for patients with advanced gastric cancer has generally been accepted in Japan, discontinuations of treatment have been reported due to grade 3 or more adverse events. The present randomized phase II study was conducted to test whether alternate-day administration of S-1 would be comparably efficient and reduce adverse events compared with conventional daily administration in the first-line chemotherapy for advanced gastric cancer. METHODS: 132 patients with advanced gastric cancer were randomly assigned to 1:2 ratios to receive treatment with daily at a standard dose of 80 mg/m(2)/day or alternate-day administration group received S-1 on 4 days a week. The primary end point was progression-free survival (PFS), and the secondary end points were safety, overall survival, time to treatment failure (TTF), disease control rate, and response rate. RESULTS: The 6-month PFS rate of the alternate-day administration group was 20.9% and failed to show significant difference from the pre-specified threshold at 15% (p = 0.117), whereas that of the daily administration group was 39.1% and significantly higher than the threshold (p = 0.001). The hazard ratio of the alternate-day administration group compared with the daily administration group was 1.753 (95% confidence interval (CI) 1.15–2.68, p = 0.010). With regard to OS, the hazard ratio of the alternate-day administration group compared with the daily administration group was 1.487 (95% CI 0.97–2.29, p = 0.072). The median TTF were 4.2 and 2.8 months in the daily and alternate-day administration group, respectively (p = 0.007). CONCLUSION: The alternate-day administration of S-1 was not recommended as the first-line therapy for patients with advanced gastric cancer.