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The Oral Fluoropyrimidines in Cancer Chemotherapy

Division of Hematology and Oncology [E. B. L., R. L. S.], Department of Medicine, the Robert Wood Johnson Clinical Scholars Program [E. B. L.], and the Cancer Research Center [R. L. S.], University of Chicago, Chicago, Illinois 60637

A classic example of a rationally developed class of anticancer drugs, the fluoropyrimidines are now the focus of further rational approaches to cancer chemotherapy as they are transformed into oral formulations. Given alone, oral 5-fluorouracil (5-FU) has erratic absorption and nonlinear pharmacokinetics. However, when oral 5-FU is given as a prodrug and/or paired with a dihydropyrimidine dehydrogenase inhibitor, the resultant 5-FU has linear pharmacokinetics that may approximate the less myelosuppressive continuous i.v. infusion schedule of 5-FU administration without the use of infusion catheters and pumps. We review the preclinical and clinical experience of several of the oral fluoropyrimidines.

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