title: Augmentation of the chemotherapeutic effectiveness of UFT, a combination of tegafur [1-(2-tetrahydrofuryl)-5-fluorouracil] with uracil, by oral l-leucovorin.
abstract: 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.
authors.affiliation: Anticancer and Antimicrobials Research Lab, Taiho Pharmaceutical Co., Ltd, Tokushima, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Okabe
authors.forename: T
authors.initials: T
authors.lastname: Toko
authors.forename: H
authors.initials: H
authors.lastname: Saito
authors.forename: K
authors.initials: K
authors.lastname: Nakano
authors.forename: A
authors.initials: A
authors.lastname: Fujioka
authors.forename: C
authors.initials: C
authors.lastname: Yuasa
authors.forename: S
authors.initials: S
authors.lastname: Takeda
authors.forename: N
authors.initials: N
authors.lastname: Unemi
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D004338:Drug Combinations; D004357:Drug Synergism; D005260:Female; D006801:Humans; D002955:Leucovorin / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008813:Mice, Inbred ICR; D009374:Neoplasms, Experimental / Q000188:drug therapy; D005641:Tegafur / Q000008:administration & dosage; D014407:Tumor Cells, Cultured; D014498:Uracil / Q000008:administration & dosage
chemical_list: D004338:Drug Combinations; C096910:UFT(R) drug; D005641:Tegafur; D014498:Uracil; D002955:Leucovorin