Biochemical and clinical pharmacology of 5-fluorouracil

The cellular and clinical pharmacology of fluoropyrimidines is characterized by marked interpatient variability in tumor response and patient tolerance. Understanding the metabolic pathways followed by 5-fluorouracil (5-FU) has led to new strategies to optimize therapy with these important agents. The "fluoropyrimidine phenotype" of tumor cells can be used to determine whether therapy with these agents is appropriate and, if so, whether one fluoropyrimidine may offer a particular advantage over another. Combining a dihydropyrimidine dehydrogenase inhibitor with 5-FU offers the potential to minimize pharmacokinetic variability and, in that way, to improve oral bioavailability, facilitate dosage adjustment to achieve desired concentrations, and increase the likelihood of tumor response while minimizing the risk of severe toxicity to individual patients.