A phase II and pharmacokinetic study of first line S-1 for advanced gastric cancer in Taiwan

Purpose: To evaluate the efficacy, safety and pharmacokinetic profiles of S-1, which composed of tegafur (FT, a prodrug of 5-FU), 5-chloro-2,4- dihydroxypyridine and potassium oxonate (Oxo), in Taiwanese advanced gastric cancer (AGC) patients. Methods: Patients with chemo-naïve, histologically confirmed AGC were eligible. S-1 was given orally at dose of 40, 50 or 60 mg, twice daily for patients with body surface 1.5 m ², respectively, on day 1-28 every 42 days/cycle. Results: Thirty-four patients were included. On intent-to-treat analysis, the overall response rate, median progression-free and overall survival were 35.3% [95% confidence interval (CI): 19.2-51.3%], 2.9 (95% CI: 2.4-5.8) months and 9.8 (95% CI: 6.1-NA) months, respectively. The most common grade 3-4 toxicities were anemia 23.5% and neutropenia 11.8%. There were two treatment-related mortality, which occurred in patients with suboptimal renal function underestimated by serum creatinine level at study entry. Single-dose pharmacokinetic study showed trend toward lower AUC_5-FU, and higher AUC_FT and AUC _Oxo comparing to most Western reports. Conclusions: The efficacy, toxicity and pharmacokinetic profiles of S-1 in current study are compatible with those from other Asian populations. Accurate renal function assessment and more closely monitoring is mandatory for S-1 therapy in patients with low body mass. Literature review suggests that, besides AUC_5-FU, AUC _Oxo may also attribute to the difference in the compliance to S-1 between Asian and Caucasian populations.