A multicenter phase II study of preoperative concurrent chemoradiotherapy with S-1 plus irinotecan for locally advanced rectal cancer: SAMRAI-2

Abstract

Background: We previously conducted a phase I study of preoperative concurrent chemoradiotherapy combining S‐1 and irinotecan with radiotherapy of the lesser pelvis in patients with resectable, locally advanced rectal cancer (SAMRAI‐1 Trial). The maximum tolerated dose (MTD) of irinotecan was 80 mg/m2, and the recommended dose was 60 mg/m2. We thus conducted a phase II study (SAMRAI‐2 Trial) to further evaluate efficacy and safety. Methods: We studied patients 20‐80 years of age with a performance status of 0 or 1 who had clinical stage T3 or T4, N0‐N2, resectable cancer (adenocarcinoma) of the upper rectum (Ra) or lower rectum (Rb). The treatment schedule was irinotecan 60 mg/m2 on days 1, 8, 22, and 29; S‐1 80 mg/day (body surface area, <1.25 m2), 100 mg/ day (≥1.25 m2 to <1.5 m2), or 120 mg/day (≥1.5 m2) on days 1‐5, 8‐12, 22‐26, and 29‐33; and radiotherapy 1.8 Gy/day on days 1‐5, 8‐12, 15‐19, 22‐26, and 29‐33 (total, 45 Gy). The primary endpoint was the pathological complete response (pCR) rate. Assuming a threshold pCR rate of 10% with an expected value of 25%, a power of 90%, and a one‐sided alpha level of 10%, we set the target number of patients at 40. Results: From October 2013 through February 2015, 43 patients were enrolled, and 41 were eligible and treated. The mean age was 57.9 years (range, 41 to 72). The male: female ratio was 30:11. The disease stage was IIA in 15 patients, IIB in 0, IIC in 1, IIIB in 23, and IIIC in 2. The tumor site was Rb in 24 patients, Rab in 7, Rba in 4, and RbP in 6. The pCR rate determined by a central review panel was 14.6% (6/41). Forty patients underwent surgery. The curative resection (R0) rate was 92.7%, and the down‐staging rate 73.2%. The chemoradiotherapy completion rate was 78.1%. The main grade 3 adverse events were neutropenia, 12.2%; leukopenia, 9.8%; diarrhea, 12.2%; anorexia, 7.3%; and nausea, 4.9%. Conclusions: Adverse events caused by preoperative concurrent chemoradiotherapy with S‐1 and irinotecan were deemed as tolerable. Because of its higher down‐staging rate, this regimen may be clinically useful in patients with rectal cancer. Although lower than expected, the pCR rate in our study was non‐inferior to the results of previous phase III studies.