TOXICITY EVALUATION OF DIFLUOROMETHYLORNITHINE - DOSES FOR CHEMOPREVENTION TRIALS

This intergroup trial was developed to determine the toxicity of relat ively low doses of difluoromethylornithine (DFMO) administered to huma ns for 1 year, The goal was to find an appropriate DFMO dose for use i n human chemoprevention trials, Patients with resected superficial bla dder cancers were studied, Following stratification, they were randomi zed to daily DFMO doses of 0.125, 0.25, 0.5, or 1.0 g/day for a planne d period of 1 year. Patients were followed closely for evidence of dru g toxicity, Seventy-six patients were evenly randomized (19 per group) to receive each dose of DFMO. Forty-nine patients received DFMO for m ore than 200 days while 35 received the drug for greater than or equal to 350 days, No substantial drug-related toxicity was observed at any dose. DFMO doses of less than or equal to 1 g/day for periods up to 1 year appear to be without significant toxicity in most patients, This dose range may be appropriate for use in future human cancer chemopre vention trials.