Augmentation of the chemotherapeutic effectiveness of UFT, a combination of tegafur [1-(2-tetrahydrofuryl)-5-fluorouracil] with uracil, by oral l-leucovorin.

UFT, combination of tegafur [1-(2-tetrahydrofuryl)-5-fluorouracil] with uracil, is widely-used as an anti-neoplastic agent in Japan. We evaluated the anti-tumor efficacy of the combined modality of UFT with oral l-leucovorin. The augmentation of anti-tumor activity of UFT by co-administration of l-leucovorin was observed over a dose of 1.85 mg/kg (5.55 mg/m2) and was significant at a dose of 5.56 mg/kg (16.7 mg/m2). Using ten human tumor xenografts, l-leucovorin significantly enhanced the growth-suppressive ability of UFT against colon carcinoma (KM20C, Col-1) and mammary carcinoma (H-31, MX-1). Among various 5-fluorouracil (FUra) derivatives, such as UFT, 5'-deoxy-5-fluorouridine (5'-DFUR) and FUra, l-leucovorin gave the maximum augmentation to the anti-tumor activity of UFT, due to the prolonged half-life of FUra in plasma. Enhancement of the cytotoxic activity of FUra by l-leucovorin against KM20C colon carcinoma cell line was observed in a time-dependent manner at a concentration of 0.01 microM l-leucovorin. Based on these results, we conclude that the combination of UFT with oral l-leucovorin has significant antitumor activity and represents an interesting regimen to be evaluated in the clinical setting.