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 <1.25, 1.25-1.5 and >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.