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.