PREOPERATIVE CHEMORADIOTHERAPY FOR RECTAL CANCER: RANDOMIZED TRIAL COMPARING ORAL URACIL AND TEGAFUR AND ORAL LEUCOVORIN VS. INTRAVENOUS 5-FLUOROURACIL AND LEUCOVORIN

Purpose To compare, in a randomized trial, 5-fluorouracil (FU) plus leucovorin (LV) (FU+LV) vs. oral uracil and tegafur (UFT) plus LV (UFT+LV) given concomitantly with preoperative irradiation in patients with cT3–4 or N+ rectal cancer. Methods and Materials A total of 155 patients were entered onto the trial. Patients received pelvic radiotherapy (4500–5,040 cGy in 5 to 6 weeks) and chemotherapy consisting of two 5-day courses of 20 mg/m 2 /d LV and 350 mg/m 2 /d FU in the first and fifth weeks of radiotherapy (77 patients) or one course of 25 mg/d oral LV and 300 mg/m 2 /d UFT for 4 weeks beginning in the second week of radiotherapy (78 patients). The primary endpoints were pathologic complete response (pCR) and resectability rate. Secondary endpoints included downstaging rate, toxicity, and survival. Results Grade 3–5 acute hematologic toxicity occurred only with FU+LV (leukopenia 9%; p = 0.02). There were no differences in resectability rates (92.1% vs. 93.4%; p = 0.82). The pCR rate was 13.2% in both arms. Tumor downstaging was more frequent with UFT+LV (59.2% vs. 43.3%; p = 0.04). Three-year overall survival was 87% with FU+LV and 74% with UFT+LV ( p = 0.37). The 3-year cumulative incidences of local recurrence were 7.5% and 8.9%, respectively ( p = 0.619; relative risk, 1.46; 95% confidence interval 0.32–6.55). Conclusion Although this study lacked statistical power to exclude clinically significant differences between both groups, the outcome of patients treated with UFT+LV did not differ significantly from that of patients treated with FU+LV, and hematologic toxicity was significantly lower in the experimental arm.