Phase I Study of the Combination of Disulfiram with Cisplatin

Abstract

In light of preclinical evidence that disulfiram and related compounds decrease the toxicity and increase the therapeutic index of cisplatin, 12 patients were treated with a combination of cisplatin and oral disulfiram to determine the maximum tolerated dose of disulfiram that could be combined with cisplatin 100 mg/m², and to determine the dose-limiting toxicity of disulfiram in this combination. Reversible confusion was the dose-limiting toxicity at a disulfiram dose of 3,000 mg/m² administered 1 h before the end of a 2-h cisplatin infusion. A randomized study of cisplatin with or without disulfiram 2,000 mg/m² p.o. is currently being conducted to determine the effect of disulfiram on cisplatin toxicity and pharmacology.