A Phase II Trial of Preoperative Chemoradiotherapy with Oral DPD-Inhibitory Fluoropyrimidines in Patients with Advanced Rectal Cancer

Abstract

Background: Preoperative chemoradiotherapy (CRT) with 5-FU has been widely used to improve local control of disease and to preserve anal sphincter in the treatment of rectal cancer. UFT and S-1 as oral dihydropyrimidine dehydrogenase (DPD)-inhibitory fluoropyrimidines enhance the therapeutic effect of 5-FU by modulating its metabolic pathways. The purpose of this study was to evaluate the efficacy and toxicity of CRT using UFT versus S-1 in patients with locally advanced rectal cancer. Methods: Fifty-nine patients who received preoperative CRT (40 Gy radiotherapy) were randomly assigned to either UFT or S-1 groups. UFT and S-1 were administered during the radiotherapy course. Response to CRT was determined using a histopathologic examination and RECIST of surgically resected specimens and classified as responders (CR, PR and Grade 2, 3) or nonresponders (SD, PD and Grade 0, 1). Results: All patients were randomly allocated to S-1 group (n = 30) or UFT group (n = 29). Pathological response rate (Grade 2 and Grade 3) was 57% in the S-1 group and 45% in the UFT group (p = 0.36). Pathological complete response (CR) rate (Grade3) was 7% in the S-1 group and 4% in the UFT group (p = 0.98). There was no statistically significant difference between the two groups in regard to the response rate of RECIST (p = 0.52). There was no statistically significant difference between the groups based on the downstaging rate, resection of tumor, sphincter preservation and marginal invasion. The incidence of Grade 3 diarrhea was significantly more frequent in the S-1 group (7%) compared with the UFT group (0%) (p = 0.02). Conclusion: The results supported the conclusion that CRT using UFT or S-1 is effective and feasible for patients with locally advanced rectal cancer.

Long-term outcomes and prognostic factors of preoperative chemoradiotherapy with oral dihydropyrimidine dehydrogenase inhibitory fluoropyrimidines in patients with locally advanced rectal cancer

“…The pathologic complete response rate was 7% in the S-1 group and 4% in the UFT group. The incidence of grade 3 diarrhea was reported in the UFT group (0%) and the S-1 group (7%), indicating that CRT using UFT or S-1 is effective and feasible for patients with locally advanced rectal cancer [7]. In the present study, we analyzed long-term outcomes, prognostic factors for overall survival (OS) and disease-free survival (DFS), and local recurrence factors in patients who received UFT-and S-1-based preoperative CRT at our hospital.…”

Prediction of response to preoperative chemoradiotherapy and establishment of individualized therapy in advanced rectal cancer

“…We previously performed a phase I clinical study and determined the recommended dose (80 mg/m 2 ) of tegafur/gimeracil/ oteracil (S-1) for preoperative CRT (4). We then undertook a phase II clinical study to evaluate the efficacy and toxicity of preoperative CRT using tegafur-uracil (UFT; 300 mg/m 2 /day) vs. S-1 (80 mg/m 2 /day) in 59 patients with locally advanced rectal cancer (5). This is the first study to use S-1 as a single agent for CRT of locally advanced rectal cancer.…”