DRUG-INTERACTION EFFECTS ON ANTITUMOR DRUGS .13. AMELIORATION OF CISPLATIN LETHALITY AND RENAL TOXICITY BY CHLORPROMAZINE IN MICE

We investigated the possibility that chlorpromazine (CPZ), an antiemet ic frequently used to control nausea and vomiting in cancer patients r eceiving chemotherapy, might modify the progression of the renal toxic ity and lethality of cisplatin (CDDP). In mice the preadministration o f CPZ (i.p.) 1 h prior to CDDP (i.p.) injection efficiently reduced no t only the lethal toxicity, but also the renal (indicated by increased blood urea nitrogen values) and intestinal toxicity (indicated by the incidence of diarrhea) which are usually observed in mice treated wit h CDDP alone. To further study the apparent protective activity of CPZ against CDDP nephrotoxicity we chose rats a species more commonly use d as a model for nephrotoxicity. In F344 rats, CPZ ameliorated CDDP-in duced increases in blood urea nitrogen (BUN), urine glucose, protein a nd lactate dehydrogenase (LDH). The preadministration of CPZ had no ob served effect on the antitumor activity of CDDP in mice inoculated i.p . with Sarcoma 180, EL4 lymphoma, or P-388 leukemia cells. The present study suggests that CPZ may be of therapeutic benefit when used with CDDP. This study also provides a rational basis for the selection of a ntiemetic therapy.