Randomized phase II trial of first-line treatment with tailored irinotecan plus S-1 therapy versus S-1 monotherapy for advanced or recurrent gastric carcinoma (JFMC31-0301) Running head: Tailored IRIS vs. S-1 as first-line therapy for gastric cancer

Objective: The pharmacokinetics of irinotecan vary markedly between individuals. This study sought to compare tailored irinotecan plus S-1 therapy with S-1 monotherapy for the treatment of patients with advanced/recurrent gastric cancer. Methods: Patients with advanced/recurrent gastric cancer were randomized to receive tailored irinotecan plus S-1 (arm A) or S-1 alone (arm B). Arm A received S-1 (80−120 mg/m/day) for 14 days, with irinotecan on days 1 and 15. The initial irinotecan dose of 75 mg/m (Level 0) was adjusted for toxicity during the previous course. In arm B, S-1 (80−120 mg/day) was administered alone for 28 days, followed by 14 days without therapy. Results: Ninety-five patients were randomized (48 to arm A and 47 to arm B). The response rate of the primary tumor (Japanese criteria) was 25.0% in arm A (12/48) and 14.9% in arm B (7/47), while the response rates according to Response Evaluation Criteria In Solid Tumors (RECIST) were 27.8% (10/36) versus 21.9% (7/32). Hematological toxicity, anorexia, and diarrhea were significantly more common in arm A, but both arms had similar grade 3−4 toxicities. Conclusion: These findings suggest the usefulness of tailored irinotecan plus S-1 therapy for gastric cancer.