Antimetabolites.

Research efforts over the past year further elucidate the determinants of sensitivity and mechanisms of resistance to the antimetabolites fluorouracil, methotrexate, and cytarabine. Progress has been made in clarifying the complex regulation of target enzyme expression for these antimetabolites. Advances in analytical methodology should facilitate quantitation of thymidylate synthase content in tumor tissue prior to and following fluorouracil-based therapy. Information concerning the basis for certain drug interactions may guide rational dose rates and schedules for clinical trials. A better understanding of the clinical pharmacology of these agents has suggested strategies to minimize their toxicity while maintaining therapeutic activity.