A phase II study of oral S-1 with pharmacokinetics and pharmacogenomic investigation in advanced or recurrent gastric cancer

4072 Background: Present study describes the first phase II study of S-1 including pharmacokinetic and pharmacogenomic evaluation for extra-Japanese Asian population with advanced gastric cancer. Methods: Chemo-naive advanced gastric cancer with measurable disease was enrolled. Initial dose of S-1 was b.i.d. at 35, then 40 mg/m2 according to devised dosing method (range, 90–160 mg/day) for 28 days every 6 weeks. Pharmacokinetic study was performed after 28-day administration at cycle 1 and 3. Microarray based CGH was performed with genomic DNA from peripheral mononuclear cells to detect the toxicity-related genetic changes. Results: When first 31 patients were enrolled, protocol was amended to conduct the study by two steps for additional patients at 40 mg/m2 without dose escalation in initial 31 patients of 35 mg/m2, because these patients showed neither significant nor cumulative toxicity. Of 62 patients enrolled, median relative dose intensity was 0.99. Overall response rate was 19.3% (95% CI, 9.2–29.5). With 558-day follow-up duration, median TTP and OS were 126 and 264 days, respectively. One-year survival rate was 33.9%. Toxicity increased with dose escalation, but there was no grade 4 toxicity. The most common significant toxicity was anemia. Pharmacokinetics parameters were similar to those of Japanese population. In microarray-CGH, we selected 18 genes with different copy numbers of 13 amplified and 5 deleted genes in patients with anemia. Conclusions: Our phase II study showed the feasibility of S-1 in gastric cancer at the dose of 35 mg/m2, and we suggested that selected 18 genes might be candidate markers for predicting anemia with S-1 treatment. No significant financial relationships to disclose.