PHASE-II TRIAL OF URACIL AND TEGAFUR PLUS ORAL LEUCOVORIN - AN EFFECTIVE ORAL REGIMEN IN THE TREATMENT OF METASTATIC COLORECTAL-CARCINOMA

Purpose: To determine the activity and evaluate the toxicity of uracil and tegafur in a 4:1 molar concentration (UFT; Taiho Pharmaceutical L td, Tokyo, Japan) plus oral calcium leucovorin in the treatment of pat ients with advanced colorectal carcinoma. Patients and Methods: Forty- five patients with advanced, bidimensionally measurable metastatic col orectal carcinoma were enrolled onto the trial. None of the patients h ad received prior chemotherapy or biologic therapy for advanced diseas e. Patients received either 350 or 300 mg/m(2)/d UFT plus 150 mg/d leu covorin administered orally in divided daily doses every 8 hours for 2 8 days followed by a 7-day rest period. Response wets evaluated after two courses of therapy. Results: Eighteen patients (three treated at 3 50 mg/m(2)/d and 15 at 300 mg/m(2)/d) had partial responses, and one p atient had a complete response (response rate, 42.2%; 95% confidence i nterval, 28% to 58%). Responses were observed in sites that included l iver (n = 18), lung (n = 6), and bone (n = 1). Of seven patients who r eceived 350 mg/m(2) UFT, prolonged grade 3 diarrhea developed in five; this resulted in a reduction in the UFT starting dose to 300 mg/m(2)/ d in the remaining 38 patients. Grade 1 or 2 toxic effects included di arrhea, nausea, vomiting, abdominal cramping, anorexia, fatigue, oral mucositis, excessive lacrimation, and rash. Among 38 patients who rece ived the 300-mg/m(2)/d dose, grade 3 toxic reactions included diarrhea (n = 4), vomiting (n = 2), abdominal cramping (n = 1), and fatigue (n = 2). Conclusion: UFT 300 mg/m(2)/d plus oral leucovorin 150 mg/d adm inistered for 28 days demonstrated significant activity against metast atic colorectal carcinoma. This oral regimen was well tolerated and de void of the neutropenia or significant oral mucositis that complicates intravenous schedules of fluorouracil (5-FU) plus leucovorin. The res ults of this clinical trial will serve as the basis for a randomized p hase III study to compare this oral schedule of UFT plus leucovorin wi th intravenous 5-FU plus leucovorin to determine the relative efficacy , impact on quality of life, and cost of the two regimens. (C) 1994 by American Society of Clinical Oncology.