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

Hiroaki Tsujimoto, Sayaka Tsukioka, Katsuhisa Koizumi, Fumio Nakagawa, Junji Uchida, Yoshikazu Sugimoto, Toshinori Oka, Masakazu Fukushima, Toshiaki Watanabe

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2 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)413-418
Number of pages6
JournalGan to kagaku ryoho. Cancer & chemotherapy
Volume34
Issue number3
Publication statusPublished - 2007 Mar
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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