Selective inhibition of the nephrotoxicity of cis-dichlorodiammineplatinum(II) by WR-2721 without altering its antitumor properties.

Abstract

Injection of 200 mg/kg of body weight of WR-2721 30 minutes before graded doses of cis-dichlorodiammineplatinum(II) (cisplatin) increased the resistance of Fischer 344 rats to cisplatin-induced nephrotoxicity by a factor of 1.7, but did not alter the sensitivity of three different transplanted tumors to cisplatin-induced growth delay. As a consequence, it was possible to administer doses of cisplatin which would have been lethal in the absence of WR-2721 injection, resulting in a proportionally greater tumor response. WR-2721 can, therefore, increase the effectiveness of cisplatin therapy through selective protection against the toxic side effects of chemotherapy.