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.
Highlights
Advanced rectal cancer carries a poorer prognosis than advanced colon cancer
All patients were randomly allocated to S-1 group (n = 30) or UFT group (n = 29)
5-Fluorouracul (5-FU) is a chemotherapeutic agent widely used for CRT of locally advanced rectal cancer. 5-FU is phosphorylated into active metabolites and kills tumor cells mainly through inhibition of thymidylate synthase (TS), which is a key enzyme in de novo DNA synthesis. 5-FU is degraded by dihydropyrimidine dehydrogenase (DPD), and high DPD activity that promotes 5-FU degradation as well as high TS activity that
Summary
Advanced rectal cancer carries a poorer prognosis than advanced colon cancer. Locoregional recurrence after resection of rectal cancer is difficult to treat and is associated with severe debilitating symptoms. Years was significantly better in patients who received chemoradiotherapy (CRT) than in those who received radiotherapy alone [3] In response to these outcomes, preoperative CRT has been widely used to improve local control of disease and to preserve anal sphincter in the treatment of locally advanced rectal cancer. A Phase II Trial of Preoperative Chemoradiotherapy with Oral DPD-Inhibitory Fluoropyrimidines in Patients with Advanced Rectal Cancer cannot be inhibited by 5-FU may cause reduced antitumor effect of 5-FU. 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. Conclusion: The results supported the conclusion that CRT using UFT or S-1 is effective and feasible for patients with locally advanced rectal cancer
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