BIOLOGIC AGENTS AS BIOCHEMICAL MODULATORS - PHARMACOLOGICAL BASIS FORTHE INTERACTION OF CYTOTOXIC CHEMOTHERAPEUTIC DRUGS AND INTERFERON

Biochemical modulation of cytotoxic cancer chemotherapeutic agents is one means of enhancing the activity and selectivity of antitumor drugs . Traditionally this approach has utilized detailed information regard ing a particular enzymatic reaction or biochemical pathway to develop potential modulating agents. In contrast, the reported clinical therap eutic activity of IFN in combination with cytotoxic agents has prompte d a reexamination of the biochemical actions of the cytokine. Interfer on elicits a number of cellular actions that might contribute to its p harmacologic activity, including both direct antitumor effects and hos t-mediated actions. The best understood are those related to the cytot oxicity of the fluoropyrimidine antimetabolites and include enzymatic reactions involved in fluoropyrimidine metabolic activation, catabolis m, and interaction with its target enzyme. However, even in this insta nce, a mechanistic association of a specific pharmacologic action with therapeutic activity remains to be determined. These studies demonstr ate that cytokines and other biologic agents may exert specific bioche mical modulations that augment (or potentially attenuate) the activity of the cytotoxic chemotherapeutic agents.