Mechanisms of action and modulation of fluorouracil

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Abstract

Fluorouracil (5-FU) and 5-fluoro-2'-deoxyuridine (FdUrd) are commercially available fluorinated pyrimidine analogues. 5-FU has antitumor activity against adenocarcinomas arising in the breast, gastrointestinal tract, and ovary, and against squamous cell carcinomas arising in the head, neck, and esophagus, with single-agent response rates of 10% to 30%. FdUrd has mainly been used for hepatic arterial infusions for patients with isolated hepatic metastases, with response rates of 42% to 62% as first-line therapy for colorectal cancer patients and 30% in those failing prior systemic 5-FU-based therapy. An appreciation for the factors influencing the cellular pharmacology of 5-FU has generated interest in combining it with both modulatory agents that enhance its metabolism or cytotoxic effects and other antineoplastic agents or modalities, such as cisplatin, methotrexate, and ionizing radiation, with which it can produce synergistic cytotoxicity. The preclinical and clinical pharmacology of 5-FU is reviewed, and novel approaches to permit oral administration as a means of mimicking protracted infusional schedules are discussed. This is a U.S. government work. There are no restrictions on its use.

Original languageEnglish (US)
Pages (from-to)249-259
Number of pages11
JournalSeminars in Radiation Oncology
Volume7
Issue number4
DOIs
Publication statusPublished - Jan 1 1997

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ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

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