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

Masanori Hotchi, Hiroshi Okitsu, Murato Miura, Madoka Hamada, Yasuhide Sonaka, Yoh Fukuda, Tsutomu Ando, Shinji Kuratate

Department of Surgery, Kochi Health Sciences Center, Kochi, Japan.
Department of Surgery, National Hospital Organization Kochi National Hospital, Kochi, Japan.
Department of Surgery, Shikoku Central Hospital, Ehime, Japan.
Department of Surgery, Takamatsu City Hospital, Takamatsu, Japan.
Department of Surgery, Tokushima Municipal Hospital, Tokushima, Japan.
Department of Surgery, Tokushima Prefectural Central Hospital, Tokushima, Japan.
Department of Surgery, Tokushima Red Cross Hospital, Tokushima, Japan.
Department of Surgery, Tokushima University Hospital, Tokushima, Japan.

DOI: 10.4236/jct.2012.326127                

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 (Grade2 and Grade3) 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.

Keywords

S-1; UFT; Chemoradiation; Rectal Cancer

Conflicts of Interest

The authors declare no conflicts of interest.

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