Platinum-radiation interactions.

The important chemotherapeutic agent cisplatin is currently being combined with radiation therapy (RT) in clinical protocols intended to exploit the potential for this drug to potentiate radiation-induced tumor cell kill. This paper reviews the reports from preclinical studies leading to the design of combined modality protocols and describes the effects produced when platinum complexes are combined with RT. Two interactions that are receiving considerable attention since they might produce an improved therapeutic ratio are the radiosensitization of hypoxic cells and post-RT potentiation of cell kill. This latter effect might include the inhibition of recovery from RT-induced potentially lethal or sublethal damage. However, platinum-radiation interactions are complex and probably include several mechanisms that are unknown at this time. The potential for platinum complexes will be especially promising if results of ongoing phase III combined modality trials show them to be efficacious, since it is unlikely that current protocol designs are optimal. Furthermore, second-generation platinum analogs or other metal complexes designed as potentiators of RT may prove to be more interactive with RT.