The fluoropyrimidines: biochemical mechanisms and design of clinical trials.

Our understanding of the biochemical events of fluoropyrimidine-induced cytotoxicity remains incomplete. However, we have a good perception of the activation and degradation pathways of these agents. Additionally, from studies performed in vitro we are gaining a new appreciation of the interactions between methotrexate and the fluoropyrimidines. These studies suggest that the common clinical practice of simultaneously administering methotrexate and 5-fluorouracil may be disadvantageous. Several simple scheduling modifications of combination therapies with these two drugs could lead to improved clinical efficacy and deserve further investigation.