Biologic agents as modifiers of chemotherapeutic effects

Recent papers dealing with the effect of biologic response modifiers on the therapeutic activity of anticancer drugs are reviewed. Preclinical findings indicate that both interferons and tumor necrosis factor-alpha are able to synergize with different cytotoxic drugs in increasing both tumor cytotoxicity or cytostasis in vitro and the therapeutic effect in animal models in vivo. The mechanism of such a synergy, however, has not been definitively worked out. Several clinical phase I and II trials have assessed the interactions of biologic response modifiers (mainly interferons and interleukin-2) with anticancer drugs, particularly in melanoma and renal cancer patients. Evidence of a therapeutic synergism is limited with most of the studies, indicating a lack of synergic or additive effects of the combination compared with single agents. Few phase III studies provided conflicting results. It is concluded that further studies on the combination of biologic response modifiers and chemotherapy both at preclinical and clinical levels are necessary to establish the possible synergistic or additive therapeutic effect of such a therapeutic approach.