Evaluating Difluoromethylornithine Safety and Efficacy for Non-Melanoma Skin Cancer Chemoprevention: A Systematic Review

Abstract

Introduction: Recent FDA approval of difluoromethylornithine (DFMO), an inhibitor of ornithine decarboxylase for the prevention of neuroblastoma in children, has renewed interest in this medication for the prevention of other cancers including keratinocyte carcinomas (KCs). It has been investigated for cancer chemoprevention, including neoplasms of the colon, breast, and prostate. Methods: We assessed the current body of literature that determines DFMO efficacy and safety in non-melanoma skin cancer prevention. A systematic search of PubMed Central, and Web of Sciences was performed. Results: In this analysis, 12 studies were included evaluating 1618 patients. Most patients were Caucasian 90% (1452/1618) with a mean age of 61 years, and 73% (1214/1618) had previously been diagnosed with KC. For oral DFMO, reduction in KC was significant in 24% (291/1214) of patients. Nonsignificant reduction was observed in 17% (207/1214) of patients. The remaining studies, representing 59% (716/1214) of patients explored DFMO’s pharmacological/biological effects without elucidating its direct impact on KC. Topical DFMO shows modest efficacy in reducing the number of actinic keratosis (AK), as indicated in 4 studies representing 38.12% (154/404) of patients. For patients taking the oral eflornithine, the most frequently reported adverse events included reversible ototoxicity (11% of patients) gastrointestinal disturbances (10.39%). For the topical DFMO transient local cutaneous eruptions were common impacting 28.76% (111/386) of patients. Conclusion: Current evidence highlights the lack of conclusive data supporting the efficacy of oral DFMO, making it difficult to recommend its use. Conversely, topical DFMO demonstrates more promising outcomes in preventing AKs, presenting a potentially useful alternative in select patients.