Combined treatment of radiation and cisdiamminedichloroplatinum (II): a review of experimental and clinical data

Abstract

Cis-diamminedichloroplatinum (II) (c-DDP), a highly effective cytostatic drug, is increasingly used in combination with irradiation both in the laboratory and in patients. This review aims at a critical reassessment of the potential role of this drug as a "radiosensitizer." The opinion about c-DDP being an effective hypoxic cell radiosensitizer in bacteria was substantiated in some studies on mammalian cells in culture but not in others. More powerful mechanisms of radiation enhancement, which are not yet fully explored, may be depletion of endogenous thiols, inhibition of cellular repair processes, and proliferation inhibition. The effects of c-DDP in combination with irradiation in experimental tumors seem to vary between different investigators and between different tumor systems. Occasionally, supra-additive effects have been observed in some animal tumors. This stresses the need for testing this combination treatment in various tumor types, preferentially of human origin. In normal tissues, the effects are, to a large extent, explained by independent cell killing by each agent. A substantial number of clinical pilot studies have shown that the combination treatment is feasible, but the results of ongoing phase III trials will be needed to assess the potential therapeutic benefit of this combined treatment modality.