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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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

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Leucovorin
Therapeutic Uses
Folic Acid
Colorectal Neoplasms
Rodentia
Diet
Therapeutics
Neoplasms
titanium silicide
Heterografts
Animal Models

ASJC Scopus subject areas

  • Cancer Research
  • Pharmacology

Cite this

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

In: Gan to kagaku ryoho. Cancer & chemotherapy, Vol. 34, No. 3, 03.2007, p. 413-418.

Research output: Contribution to journalArticle

Tsujimoto, Hiroaki ; Tsukioka, Sayaka ; Koizumi, Katsuhisa ; Nakagawa, Fumio ; Uchida, Junji ; Sugimoto, Yoshikazu ; Oka, Toshinori ; Fukushima, Masakazu ; Watanabe, Toshiaki. / 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. In: Gan to kagaku ryoho. Cancer & chemotherapy. 2007 ; Vol. 34, No. 3. pp. 413-418.
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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.",
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