Chemoprevention of human actinic keratoses by topical 2-(difluoromethyl)-dl-ornithine.

Abstract

Alpha-2-(Difluoromethyl)-dl-ornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase, has been shown to suppress skin carcinogenesis in murine models after oral or topical administration. We designed a randomized, placebo-controlled study using a topical hydrophilic ointment formulation with or without 10% (w/w) DFMO. Forty-eight participants with moderate-severe actinic keratoses (AKs) on their forearms (i.e., at least 10 well-circumscribed lesions on the lateral surface) completed a 1-month run-in on placebo ointment. Before randomization, all lateral forearm AKs were circled, counted, photographed, and skin biopsies were obtained for DFMO and polyamine levels. Then participants were randomized to receive DFMO ointment on the right versus the left forearm and placebo hydrophilic ointment on the contralateral forearm twice daily for 6 months. DFMO was not detected in the blood of any subject, and there were no systemic toxicities. None of a subsample of 17 placebo forearms had measurable concentrations of DFMO, whereas 13 of the corresponding DFMO-treated forearms had high DFMO skin levels. As compared with placebo, the 6-month DFMO treatment caused a 23.5% reduction in the number of AKs (P = 0.001) as well as significant suppression of AK biopsy spermidine levels (26%; P = 0.04). Seven of the 48 (14.6%) participants experienced severe (2; 4.2%) or moderate (5; 10.4%) inflammatory reactions on their DFMO-treated arms which required dosing modification. Topical DFMO for 6 months can reduce the number of AK lesions and skin spermidine concentrations in high-risk participants and deserves additional study as a skin cancer chemopreventive agent.

• Authors: D S Alberts, R T Dorr, J G Einspahr, M Aickin, K Saboda, M J Xu, Y M Peng, R Goldman, J A Foote, J A Warneke, S Salasche, D J Roe, G T Bowden
• Journal: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology (Cancer Epidemiol Biomarkers Prev) Vol. 9 Issue 12 Pg. 1281-6 (Dec 2000) ISSN: 1055-9965 [Print] United States
• PMID: 11142412 (Publication Type: Clinical Trial, Journal Article, Randomized Controlled Trial, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antineoplastic Agents
• Enzyme Inhibitors
• Ointments
• Eflornithine

Topics

• Aged
• Antineoplastic Agents (therapeutic use)
• Eflornithine (therapeutic use)
• Enzyme Inhibitors (therapeutic use)
• Female
• Humans
• Keratosis (etiology, prevention & control)
• Male
• Ointments
• Photosensitivity Disorders (etiology, prevention & control)