Abstract
5-Fluorouracil (5-FU) has been the mainstay of systemic therapy for colorectal cancer since its initial development 40 years ago. Efforts to improve the therapeutic index of 5-FU have included alteration of schedule and addition of biochemical modulators. An understanding of 5-FU mechanisms of action has resulted in major therapeutic advances in the past 10 years; however, a plateau has been reached in the efficacy of 5-FU, mandating a paradigm shift for those involved in colorectal cancer drug development. One direction vigorously pursued is the development of orally administered fluoropyrimidines that maintain or improve upon the effectiveness of intravenous 5-FU. In this paper the preclinical and clinical development of oral fluoropyrimidines and their modulators is reviewed, including UFT, capecitabine, ethynyluracil and S-1.
MeSH terms
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Administration, Oral
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Antineoplastic Agents / administration & dosage
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Antineoplastic Combined Chemotherapy Protocols / administration & dosage
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Capecitabine
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Colorectal Neoplasms / drug therapy*
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Colorectal Neoplasms / enzymology
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Deoxycytidine / administration & dosage
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Deoxycytidine / analogs & derivatives
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Dihydrouracil Dehydrogenase (NADP)
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Drug Combinations
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Enzyme Inhibitors / administration & dosage
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Fluorouracil / administration & dosage*
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Humans
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Oxidoreductases / metabolism
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Pyridines / administration & dosage
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Tegafur / administration & dosage
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Uracil / administration & dosage
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Uracil / analogs & derivatives
Substances
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Antineoplastic Agents
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Drug Combinations
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Enzyme Inhibitors
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Pyridines
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UFT(R) drug
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Deoxycytidine
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Tegafur
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eniluracil
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Uracil
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Capecitabine
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Oxidoreductases
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Dihydrouracil Dehydrogenase (NADP)
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Fluorouracil
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gimeracil