期刊
INVESTIGATIONAL NEW DRUGS
卷 18, 期 4, 页码 299-313出版社
SPRINGER
DOI: 10.1023/A:1006416410198
关键词
antimetabolites; pyrimidine analogs; thymidylate synthase
5-Fluorouracil (5-FU) and 5-fluoro-2'-deoxyuridine (FdUrd) are pyrimidine analogs that have been part of the therapeutic armamentarium for a variety of solid tumors for over forty years. 5-FU has customarily required intravenous administration due to poor and erratic oral bioavailability, while FdUrd has generally been employed for regional administration to the liver or the peritoneal cavity. A great deal of knowledge has been gained concerning the cellular pharmacology and mechanism of action of 5-FU since it was first synthesized in the late 1950's. A more thorough understanding of the factors influencing the metabolic activation of 5-FU and its cellular effects has generated considerable interest in combining it with both modulatory agents such as leucovorin and methotrexate that enhance its metabolism or cytotoxic effects. In addition, 5-FU has also been employed to enhance the therapeutic activity of other antineoplastic agents or modalities such as cisplatin and ionizing radiation with which it can synergize. Appreciation of the clinical pharmacology of 5-FU and FdUrd have led to a variety of schedules that are clinically useful. The preelinical and clinical pharmacology of 5-FU is reviewed to provide a basis for exploring the novel approaches to permit oral administration of 5-FU or its prodrugs that will be described in other articles in this issue.
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