The application of both radioprotective and radiosensitizing drugs in clinical radiotherapy is limited by the large drug doses required to obtain significant therapeutic gains. A potential means of circumventing these toxicity problems, while retaining significant therapeutic gains, would be to use small doses of both types of drugs. This possibility has been tested, using the specific drug combination WR-2721 and Ro-07-0582 with the following results: The two drugs are not additive in terms of lethal toxicity in the mouse; WR-2721 does not interfere with the ability of Ro-07-0582 to sensitize tumors in vivo; and Ro-07-0582 does not interfere with the ability of WR-2721 to protect mouse skin. While the therapeutic gains depend on the radiation dose and endpoints considered, the combination proved to be superior to either drug alone in all cases. The success of these preliminary investigations would appear to warrant further study.

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