To compare the antitumor activity of Tegafur (150 mg/kg/day) with continuous intravenous infusion of 5-fluorouracil (5-FU) (12.5 mg/kg/day) and with oral UFT® (60 mg/kg/day) with and without low- or high-dose leucovorin (50 or 200 mg/kg/day), rats with advanced colon cancer were treated with Tegafur or UFT® 3 times daily for 28 days and 5-FU by continuous intravenous infusion for 28 days. UFT® alone had a complete remission (CR) rate of 38%, whereas Tegafur and 5-FU produced no CRs. When high-dose leucovorin was added, the CR rate for UFT® increased to 75%; Tegafur plus high-dose leucovorin resulted in only a partial remission rate of 50%, with no CRs; low-dose leucovorin was not as effective as the high dose. Hence, UFT® clearly offers significant therapeutic advantages over Tegafur and protracted infusion of 5-FU. High-dose leucovorin is essential for significant modulation of drug action in this t