title: [Benefits of TS-1 plus leucovorin combination therapy for colorectal cancer: evaluation of therapeutic effect of TS-1 and leucovorin combination therapy using rodent model fed a low folate diet].
abstract: We evaluated the therapeutic effect of TS-1, a novel oral fluoropyrimidine, in combination with leucovorin with in vivo experiments using a murine tumor xenograft model fed a low folate diet. The reduced folate levels in the tumors of mice fed a low folate diet were significantly lower than those in the tumors of mice fed a normal diet. In addition, the basal reduced folate levels in the tumors of mice fed a low folate diet were comparable to those in human colorectal cancer tissues. Furthermore, when leucovorin was orally administered, the reduced folate levels in the tumors of mice fed a low folate diet were more than two-fold higher than those of mice fed the normal diet. The leucovorin-induced potentiation of TS-1 antitumor activity was obviously higher in COL-1 tumor-bearing mice fed a low folate diet than in mice fed a normal diet. The remarkable increase in reduced folate levels following the administration of leucovorin contributed to the leucovorin-induced potentiation of TS-1 antitumor activity in this low-folate-diet animal model. These results suggest that rodent models fed a low folate diet are suitable for in vivo evaluation of reduced folate drugs like leucovorin. In this model, the combination of leucovorin with TS-1 resulted in a higher antitumor efficacy than TS-1 alone or the combination of UFT and leucovorin, suggesting that TS-1 and leucovorin combination therapy may be an effective regimen for patients with colorectal cancer.
authors.affiliation: Optimal Medication Research Laboratory, Taiho Pharmaceutical Co., Ltd.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Tsujimoto
authors.forename: Sayaka
authors.initials: S
authors.lastname: Tsukioka
authors.forename: Katsuhisa
authors.initials: K
authors.lastname: Koizumi
authors.forename: Fumio
authors.initials: F
authors.lastname: Nakagawa
authors.forename: Junji
authors.initials: J
authors.lastname: Uchida
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Sugimoto
authors.forename: Toshinori
authors.initials: T
authors.lastname: Oka
authors.forename: Masakazu
authors.initials: M
authors.lastname: Fukushima
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Watanabe
mesh_terms: D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000473:pathology*; D004032:Diet; D004195:Disease Models, Animal; D004338:Drug Combinations; D004341:Drug Evaluation; D005492:Folic Acid / Q000008:administration & dosage; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010094:Oxonic Acid / Q000008:administration & dosage*; D005641:Tegafur / Q000008:administration & dosage*
chemical_list: D004338:Drug Combinations; C079198:S 1 (combination); D005641:Tegafur; D010094:Oxonic Acid; D005492:Folic Acid; D002955:Leucovorin