Radiopotentiation in a Murine Tumor (MTG-B) by Continuous Infusion Platinum

Abstract

For more than a decade, studies have shown that the chemotherapeutic drug cisplatin can interact with ionizing radiation, resulting in what is often described as a potentiation of radiation-induced cell kill (for review see Dewit 1987, and Douple 1986, 1988). At least two distinguishable effects have been identified in cell culture experiments which might account for the supra-additive therapeutic effects reported in animal tumors when the two agents are combined. The first, radiosensitization of hypoxic cells, requires that the cisplatin be present at the time of irradiation. The second, post-irradiation potentiation, enhances cell kill when the cisplatin is added shortly after irradiation, and might include an inhibition of sublethal and potentially lethal damage repair processes. These effects are not limited to the combination of only cisplatin with radiation, since other platinum complexes have also produced these effects (Nias 1985; Douple 1988), including the second generation platinum complex carboplatin, also known as paraplatin (Douple 1985; Douple et al. 1985, 1987; O’Hara et al. 1986). The precise mechanisms responsible for the interactions remain elusive, but because of the potential for therapeutic gain represented by the two effects, numerous clinical trials with varying protocols have been instituted in an effort to exploit the interactions between the two modalities (Douple 1985, 1988).