Renal damage in mice after treatment with cisplatin and x-rays: comparison of fractionated and single-dose studies.

Functional kidney damage in mice was measured after bilateral irradiation with x-rays alone or in combination with cisplatin (c-DDP). A single drug dose (6 mg/kg) was injected 30 minutes before the first of four or eight x-ray doses, given as four fractions per day with a minimum interval of 5 hours between treatments. A 30-fraction schedule was also investigated, with 15 fractions given in the first week (3 fractions per day), followed by a 2-week rest period and another 15 fractions in the fourth week. The c-DDP (4 mg/kg) was administered 30 minutes before the first fraction of each week, giving a total drug dose of 8 mg/kg. Renal function was assessed monthly from 10 to 37 weeks after the start of treatment by the clearance of 51Cr-labeled EDTA. The combined treatment caused more kidney damage than either agent alone for all fractionation schedules. Enhancement of the radiation damage by c-DDP changed only slightly with fractionation; dose enhancement factors were 1.2 for 1 fraction to 1.3 for 30 fractions. Modeling studies showed that this was consistent with the additive toxic effects of the two agents. There was no change in the alpha/beta for renal damage after x-rays plus c-DDP, compared with x-rays alone (alpha/beta = 1.9 Gy), implying that there was no reduction in repair and no modification of the x-ray response by c-DDP.