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] wit h uracil, is widely used as an anti-neoplastic agent in Japan. We eval uated the anti-tumor efficacy of the combined modality of UFT with ora l l-leucovorin. The augmentation of anti-tumor activity of UFT by co-a dministration of l-leucovorin was observed over a dose of 1.85 mg/kg ( 5.55 mg/m(2)) and was significant at a dose of 5.56 mg/kg (16.7 mg/m(2 )). Using ten human tumor xenografts, l-leucovorin significantly enhan ced the growth-suppressive ability of UFT against colon carcinoma (KM2 0C, Col-l) and mammary carcinoma (H-31, MX-1). Among various 5-fluorou racil (FUra) derivatives, such as UFT, 5'-deoxy-5-fluorouridine (5'-DF UR) and FUra, l-leucovorin gave the maximum augmentation to the anti-t umor activity of UFT, due to the prolonged half-life of FUra in plasma . Enhancement of the cytotoxic activity of FUra by l-leucovorin agains t KM20C colon carcinoma cell line was observed in a time-dependent man ner at a concentration of 0.01 mu M l-leucovorin. Based on these resul ts, we conclude that the combination of UFT with oral l-leucovorin has significant anti-tumor activity and represents an interesting regimen to be evaluated in the clinical setting.