Effect of sodium thiosulfate on cis-dichlorodiammineplatinum(II) toxicity and antitumor activity in L1210 leukemia

Abstract

Concurrent administration of sodium thiosulfate reduced the toxicity of cis-dichlorodiammineplatinum(II) (DDP) in a dose-related manner in mice. Sodium thiosulfate protected mice against an otherwise lethal dose of DDP (20 mg/kg), and reduced DDP-induced weight loss. Sodium thiosulfate (800 mg/kg) injected within 1 hour before or 1/2 hour after DDP blocked nephrotoxicity as measured by a rise in BUN, an increase in kidney weight, and medullary hemorrhage. In culture, sodium thiosulfate markedly reduced the toxicity of DDP to mouse colony-forming units. Concurrent injection of sodium thiosulfate partially reduced the antitumor activity of DDP. The therapeutic dose range of DDP was expanded, but the maximum increase in lifespan of mice bearing L1210 leukemia was reduced by 40%. Sodium thiosulfate offers the possibility of systemic protection against the cytotoxicity of regionally administered DDP in man.