A phase II and pharmacokinetic study of first line S-1 for advanced gastric cancer in Taiwan
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.
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 <1.25, 1.25–1.5 and >1.5 m2, respectively, on day 1–28 every 42 days/cycle.
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 AUC5–FU, and higher AUCFT and AUCOxo comparing to most Western reports.
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 AUC5–FU, AUCOxo may also attribute to the difference in the compliance to S-1 between Asian and Caucasian populations.
KeywordsGastric cancer S-1 Chemotherapy Pharmacokinetic study Phase II
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