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.