Optimum schedule of selenium administration to reduce lethal and renal toxicities of cis-diamminedichloroplatinum in mice.

The optimum conditions of selenium administration to reduce the side effects of a single dose of cis-diamminedichloroplatinum (cis-DDP) in mice were examined. The best effects against lethal toxicity of cis-DDP was obtained when sodium selenite was administered subcutaneously (s.c.) to mice simultaneously with s.c. injected cis-DDP at a molar ratio of 1 to 3.5 (sodium selenite to cis-DDP) on the first day and the same amount of selenite was given daily for four subsequent days. This coadministration of selenite completely depressed not only lethal toxicity of cis-DDP but also its renal toxicity (indicated by increased blood urea nitrogen values) and intestinal toxicity (indicated by the incidence of diarrhea) which were usually observed in the mice treated with cis-DDP alone. Furthermore, coadministration of selenite did not compromise the antitumor activity of cis-DDP against several transplantable tumors in mice. Therefore, the administration schedule of selenite with cis-DDP described above may be useful for cancer chemotherapy.