Effects of fractionated schedules of irradiation combined with cis-diamminedichloroplatinum II on the SCCVII/St tumor and normal tissues of the C3H/KM mouse.

The interaction of cis-diamminedichloroplatinum II (c-DDP) and a course of 5 daily irradiations was investigated in the SCCVII/St tumor and normal tissues (duodenal crypt cells and lung) of the C3H mouse. Two schedules with daily doses of 2.4 mg/kg c-DDP given immediately before 4 Gy X ray on 5 consecutive days and a single 12 mg/kg c-DDP dose followed 24 hr later by the first of 5 daily 4 Gy X ray doses produced the most consistent and significant supra-additive effects on the SCCVII tumor. This supra-additive effect was also achieved with lower and much less toxic drug doses. These schedules produced high enhancement ratios (dose effect factors DEF) for mouse duodenal crypt cells, but the degree of enhancement was less than that for the SCCVII tumor. Schedules with a 72-hr interval between drug and radiation treatments, which produced low enhancement ratios for the SCCVII tumor and duodenal crypt cells, gave high enhancement ratios for the lung. It is concluded that c-DDP has the potential of enhancing the radiation effect on normal tissues, and the degree of enhancement depends upon the interval between X ray and c-DDP. The enhancement ratios for the SCCVII tumors are greater than for normal tissues, and this results in high therapeutic gain factors (TGF). Comparing the effects on tumor with those on normal tissues, it may be seen that there is clinical usefulness in simultaneous combination treatments and perhaps moreso in the administration of a single drug dose 24 hr before the first of 5 daily X ray fractions.