PROTRACTED TREATMENT WITH TEGAFUR AND LOW-DOSE ORAL LEUCOVORIN IN PATIENTS WITH ADVANCED COLORECTAL-CARCINOMA

BACKGROUND. Protracted oral administration of tegafur (TG) and leucovo rin (LV) attempts to simulate the continuous infusion of 5-fluorouraci l, with a higher intracellular folate pool. In a prior dose-finding st udy with a fixed TG dose of 0.75 g/m(2)/day for a period of 21 days an d continuous oral LV, the recommended dose of LV was 45 mg/day in 28-d ay cycles. METHODS. Thirty-nine patients with histologic confirmation of adenocarcinoma of the colon or rectum, either advanced or metastati c disease, and who were not candidates for radical treatment were incl uded in a Phase II study using this schedule. RESULTS. One hundred six ty-three cycles of chemotherapy were delivered (median, 4 cycles per p atient). Toxicity was observed in the form of diarrhea, which was seve re in 12 patients (30.7%). Grade 3 (according to the World Health Orga nization criteria) oral mucositis was recorded in 7 patients (18%). As thenia was severe in 10% of the patients. Recuperation from toxicity w as rapid and managed primarily on an outpatient basis. Two complete (5 .1%) and 13 partial (33.3%) responses were observed, with a global res ponse index of 38.5% (95% confidence interval, 23.2-53.6%). The median overall survival was 11.3 months. CONCLUSIONS, The results of this st udy show that an all-oral regimen of tegafur and leucovorin can obtain biochemical modulation, with a significant response rate, in patients with advanced colorectal carcinoma. Randomized trials are needed to a ssess the possible advantage of this regimen over intravenous schedule s. Cancer 1998;83:254-8. (C) 1998 American Cancer Society.