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Toxicity evaluation of difluoromethylornithine: doses for chemoprevention trials
C L Loprinzi1, E M Messing, J R O'Fallon
1Mayo Clinic and Mayo Foundation, Rochester, Minnesota 55905, USA.
Abstract:
This intergroup trial was developed to determine the toxicity of relatively low doses of difluoromethylornithine (DFMO) administered to humans for 1 year. The goal was to find an appropriate DFMO dose for use in human chemoprevention trials. Patients with resected superficial bladder cancers were studied. Following stratification, they were randomized to daily DFMO doses of 0.125, 0.25, 0.5, or 1.0 g/day for a planned period of 1 year. Patients were followed closely for evidence of drug toxicity. Seventy-six patients were evenly randomized (19 per group) to receive each dose of DFMO. Forty-nine patients received DFMO for more than 200 days while 35 received the drug for > or = 350 days. No substantial drug-related toxicity was observed at any dose. DFMO doses of > or = 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 chemoprevention trials.
Insights
Difluoromethylornithine (DFMO) showed no significant toxicity in a 1-year human trial. This finding supports using DFMO at doses of 1 g/day or higher for future cancer chemoprevention studies.
Area of Science:
- Oncology
- Pharmacology
- Clinical Trials
Background:
- Superficial bladder cancer recurrence is a concern.
- Chemoprevention strategies aim to prevent cancer development or recurrence.
- Identifying safe and effective chemopreventive agents is crucial.
Purpose of the Study:
- To determine the toxicity of low-dose difluoromethylornithine (DFMO) in humans over one year.
- To establish an appropriate DFMO dosage for future human cancer chemoprevention trials.
Main Methods:
- An intergroup trial involving 76 patients with resected superficial bladder cancer.
- Randomization to four daily DFMO doses: 0.125, 0.25, 0.5, or 1.0 g/day.
- One-year administration with close monitoring for drug toxicity.
Main Results:
- No substantial drug-related toxicity was observed across all tested DFMO doses.
- Most patients tolerated DFMO doses of 1 g/day or higher for up to one year.
- Thirty-five patients received DFMO for 350 days or more, with no significant adverse events.
Conclusions:
- Difluoromethylornithine (DFMO) appears safe at doses up to 1 g/day for one year in patients with superficial bladder cancer.
- The tested dose range of DFMO is potentially suitable for future human cancer chemoprevention trials.
- Further research can explore the efficacy of DFMO in preventing cancer recurrence.