Phase I study of preoperative oral uracil and tegafur plus leucovorin and radiation therapy in rectal cancer

Purpose: preoperative combined-modality therapy for rectal cancer may allow for sphincter preservation, while decreasing recurrence rates and improvin g the overall prognosis. Oral chemotherapy with uracil and tegafur (UFT) pl us leucovorin (LV) may reduce costs and complications associated with protr acted infusions of fluorouracil. Our goal was to evaluate the safety of UFT plus LV combined with preoperative radiation and determine the maximum-tol erated dose (MTD) and dose-limiting toxicity (DLT) of UFT plus LV in this s etting. Patients and Methods: patients with tumor-node-metastasis stage II or III r ectal cancer received escalating doses of UFT (starting at 250 mg/m(2)/d, w ith 50-mg/m(2)/d increments between consecutive cohorts) and fixed doses of LV (90 mg/d). The UFT and LV combination was given 5 days per week concurr ently with ct 5-week course of preoperative radiation totaling 45 Gy (1.8 G y/fraction). Surgery was performed 4 to 6 weeks after radiation and was fol lowed by four 35-day cycles of fixed doses of UFT and LV (28 days of therap y each cycle). Results: Fifteen patients were treated, and 13 received the full preoperati ve chemotherapy. All planned radiation was delivered successfully. The MTD of UFT with radiation was 350 mg/m(2)/d with 90 mg/d of LV. Diarrhea was th e DLT. Sphincter-preserving surgery was performed in 12 of 14 patients. One patient had progressive disease before surgery. Pathologic evolvation of 1 4 resected specimens showed a complete response in three cases. Conclusion: Preoperative chemoradiation with oral UFT plus LV is feasible a nd well tolerated and should be further investigated. (C) 2000 by American Society of Clinical Oncology.