A multicenter phase I study of preoperative chemoradiotherapy with S-1 and irinotecan for locally advanced lower rectal cancer (SAMRAI-1).

Abstract

Preoperative 5-fluorouracil-based chemoradiotherapy is a standard treatment for locally advanced lower rectal cancer (LALRC). We performed a phase I study to develop a new regimen combining irinotecan and S-1. Patients with LALRC (T3-4, N0-2) were studied. The radiation dose was 45Gy in 25 fractions. S-1 (80mg/m(2)/day) was administered on days 1-5, 8-12, 22-26, and 29-33. Irinotecan was administered on days 1, 8, 22, and 29. The dose of irinotecan was initially 60mg/m(2) (level 1). Surgery was performed 6-10weeks after the chemoradiotherapy. Twenty patients were enrolled, of whom 18 patients were analyzed. Dose-limiting toxicity (DLT) did not occur in the first 3 patients treated with irinotecan at 80mg/m(2) (level 2), but developed in 3 of the 6 patients who received irinotecan at 90mg/m(2) (level 3). Then DLT occurred in 3 other patients at level 2. At level 2 or 3, DLT comprised neutropenia, thrombocytopenia, and diarrhea. Level 2 was designated as the maximum tolerated dose, and level 1 as a recommended dose (RD). The pathological complete response rate was 28%, and the down-staging rate was 56%. Our results suggested that the RD of irinotecan when combined with preoperative S-1 and pelvic radiation was 60mg/m(2).