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5-FU Metabolism in Cancer and Orally-Administrable 5-FU Drugs
Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, Japan
Department of Pathology, Tohoku University Hospital, Sendai, Japan
Computational Biology Research Center, National Institute of Advanced Industrial Science and Technology, Tokyo, Japan
* Author to whom correspondence should be addressed.
Received: 23 August 2010; in revised form: 14 September 2010 / Accepted: 15 September 2010 / Published: 17 September 2010
Abstract: 5-Fluorouracil (5-FU) is a key anticancer drug that for its broad antitumor activity, as well as for its synergism with other anticancer drugs, has been used to treat various types of malignancies. In chemotherapeutic regimens, 5-FU has been combined with oxaliplatin, irinotecan and other drugs as a continuous intravenous infusion. Recent clinical chemotherapy studies have shown that several of the regimens with oral 5-FU drugs are not inferior compared to those involving continuous 5-FU infusion chemotherapy, and it is probable that in some regimens continuous 5-FU infusion can be replaced by oral 5-FU drugs. Historically, both the pharmaceutical industry and academia in Japan have been involved in the development of oral 5-FU drugs, and this review will focus on the current knowledge of 5-FU anabolism and catabolism, and the available information about the various orally-administrable 5-FU drugs, including UFT, S-1 and capecitabine. Clinical studies comparing the efficacy and adverse events of S-1 and capecitabine have been reported, and the accumulated results should be utilized to optimize the treatment of cancer patients. On the other hand, it is essential to elucidate the pharmacokinetic mechanism of each of the newly-developed drugs, to correctly select the drugs for each patient in the clinical setting, and to further develop optimized drug derivatives.
Keywords: 5-FU metabolism; cell death; colon cancer; oral 5-FU drugs
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Miura, K.; Kinouchi, M.; Ishida, K.; Fujibuchi, W.; Naitoh, T.; Ogawa, H.; Ando, T.; Yazaki, N.; Watanabe, K.; Haneda, S.; Shibata, C.; Sasaki, I. 5-FU Metabolism in Cancer and Orally-Administrable 5-FU Drugs. Cancers 2010, 2, 1717-1730.
Miura K, Kinouchi M, Ishida K, Fujibuchi W, Naitoh T, Ogawa H, Ando T, Yazaki N, Watanabe K, Haneda S, Shibata C, Sasaki I. 5-FU Metabolism in Cancer and Orally-Administrable 5-FU Drugs. Cancers. 2010; 2(3):1717-1730.
Miura, Koh; Kinouchi, Makoto; Ishida, Kazuyuki; Fujibuchi, Wataru; Naitoh, Takeshi; Ogawa, Hitoshi; Ando, Toshinori; Yazaki, Nobuki; Watanabe, Kazuhiro; Haneda, Sho; Shibata, Chikashi; Sasaki, Iwao. 2010. "5-FU Metabolism in Cancer and Orally-Administrable 5-FU Drugs." Cancers 2, no. 3: 1717-1730.