title: [Antitumor activity and function of S-1, a new oral tegafur-based formulation].
abstract: TS-1 (S-1), developed by the scientific theory of both potentiating antitumor activity of 5-fluorouracil (5-FU) and reducing gastrointestinal toxicity induced by 5-FU, is a new oral formulation consisting of 1 M tegafur, 0.4 M gimeracil and 1 M oteracil potassium. We investigated the antitumor efficacy of S-1 alone and in combination with other cytotoxic anticancer drugs using subcutaneously or orthotopically implanted murine and human tumors in rodents. As a single agent, S-1 showed higher antitumor activity with its low intestinal toxicity compared to continuous venous infusion 5-FU, the most effective dosing method of 5-FU, and/or to clinically available oral fluoropyrimidines such as UFT, doxyfluridine and capecitabine on various murine tumors and human tumor xenografts. Especially, it was noteworthy that S-1 as a DPD-inhibitory fluoropyrimidine markedly affected human tumor xenografts with high expression levels of DPD on which other fluoropyrimidines showed a low antitumor activity. In combination with other anticancer drugs such as CPT-11 and taxanes, S-1 exercised synergistic antitumor efficacy not only on 5-FU-sensitive tumors with low expression levels of thymidylate synthase (TS) but also on 5-FU-resistant tumors with originally higher and/or elevated levels of TS expression. As one of the reasonable mechanism of antitumor synergism by the combination, CPT-11 and taxanes were found to reduce the expression of TS in human tumor resistant to 5-FU with high expression TS levels. Throughout our preclinical antitumor studies of S-1, alone and/or in combination with other anticancer drugs, it would be expected to contribute greatly to the treatment of cancer patients.
authors.affiliation: Tokushima Research Center, Taiho Pharmaceutical Co., Ltd., Japan.
authors.forename: Masakazu
authors.initials: M
authors.lastname: Fukushima
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000964:Antimetabolites, Antineoplastic; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use; D002945:Cisplatin / Q000008:administration & dosage; D004334:Drug Administration Schedule; D004338:Drug Combinations; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D051379:Mice; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D010094:Oxonic Acid / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology*; D004364:Pharmaceutical Preparations; D051381:Rats; D012517:Sarcoma, Yoshida / Q000188:drug therapy; D005641:Tegafur / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology*; D014498:Uracil / Q000008:administration & dosage
chemical_list: D000964:Antimetabolites, Antineoplastic; D004338:Drug Combinations; D004364:Pharmaceutical Preparations; C079198:S 1 (combination); D005641:Tegafur; D014498:Uracil; D010094:Oxonic Acid; D002945:Cisplatin; D005472:Fluorouracil