A phase I study of oral UFT given concomitantly with standard preoperative radiotherapy for rectal cancer

Background: Preoperative radiotherapy is standard treatment for rectal cancer and is often combined with 5-fluorouracil-based chemotherapy. UFT, a new oral 5FU derivative, given daily during a course of radiotherapy mimics the effect of continuous-infusion 5FU. Objectives: To determine the maximum tolerated dose of oral UFT and leucovorin with preoperative pelvic irradiation for rectal cancer, and assess tumor response. Methods: In this phase 1 trial, 16 patients aged 42-79 years with tumors within 12 cm of the anal verge received radiotherapy, 45 Gy over 5 weeks, an escalating dose of oral UFT, and a fixed dose of 30 mg/day leucovorin. UFT and leucovorin were given for 28 consecutive days concomitant with the first 4 weeks of radiotherapy. Surgery was scheduled for 4-6 weeks after completion of radiotherapy. The surgical procedure was determined by the surgeon at the time of surgery. Results: No grade III toxicity was seen at 200 mg/m(2)/day UFT. Of eight patients who received 240 mg/m(2)/day LIFT, one developed grade IV diarrhea; of four patients who received 270 mg/m(2)/day UFT, one was hospitalized with grade IV diarrhea and leukopenic fever and died during hospitalization. Of the 15 evaluable patients, 9 had pathologic tumor downstaging including 4 patients with complete response. Only one patient required a colostomy. Conclusions: The MTD of UFT together with leucovorin and preoperative radiotherapy for rectal cancer is 240 mg/m(2). The major toxicity was diarrhea. Downstaging was noted in 60% of patients, allowing sphincter-preserving surgery even in patients with low tumors.