Efficacy and Safety of Preoperative Chemoradiotherapy With S-1 for Advanced Rectal Cancer: A Phase II Study

Abstract

Background: Preoperative chemoradiotherapy (CRT) for patients with rectal cancer has not yet been established in Japan. We conducted a non-randomized phase II study to evaluate the efficacy and safety of preoperative CRT with S-1, a fixed-dose combination of tegafur, gimeracil, and oteracil potassium. Methods: We conducted a prospective, interventional, single-center study. Radiotherapy was administered at a total dose of 45 Gy (1.8 Gy in 25 fractions) for five weeks. S-1 was administered orally for a total of nine weeks (five weeks during and four weeks after radiotherapy) at a dose of 80 mg/m2/day. The endpoint was the pathological complete response (pCR) rate. The required sample size was calculated to be 30 individuals. The characteristics of the 28 patients included were as follows: cStage (II:12/ III:16), median age of 66 years (range 40–77 years), male/female (20/8), and lesion site (Ra-Rb:3/Rb:23/Rb-P:2). Results: Preoperative treatment was completed in 27 patients (96%). Treatment abandon was because of diarrhea. Grade 3 or higher adverse events were observed in only two patients (7%). Clinical downstaging was performed in eight patients (29%). Radical resection was achieved in 27 patients (96%), including 19 (68%) who underwent sphincter-preserving surgery. The pCR rate was 11% (three patients). The three-year disease-free survival rate was 79%, and the overall survival was 89%. No local recurrence occurred three years after surgery. Conclusions: Preoperative CRT with S-1 has an acceptable safety profile, and can potentially contribute to preserving anal function in patients with rectal cancer.Trial registration: UMIN Clinical Trial Registry: UMIN000013598. Registered 1 April 2014, https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000015887