A Phase III Skin Cancer Chemoprevention Study of DFMO: Long-term Follow-up of Skin Cancer Events and Toxicity

Decreasing the incidence of nonmelanoma skin cancer (NMSC) is of great importance in regards to future healthcare services. Given the previously reported preventive effects of alpha-difluoromethylornithine (DFMO) in skin and colon cancer trials, we determined appropriate cause to update the clinical data on the subjects from the recently reported randomized, double-blind, placebo-controlled phase III skin cancer prevention study of DFMO. Our intention was to retrospectively assess the further incidence of skin cancer, other malignancies, and adverse events of patients accrued to our phase III skin cancer prevention study of DFMO. Clinical records of 209 University of Wisconsin (UW) Health subjects were reviewed, and 2,092.7 person years of on study (884.3 person years) and poststudy (1,208.4 person years) follow-up for these patients were assessed for new NMSC events and recurrence rates from the on study period, the poststudy period, and the two study periods combined. No evidence of increased significant diagnoses or serious adverse events was observed in the DFMO participants. The initially observed, marginally significant reduction (P = 0.069) in NMSC rates for DFMO subjects relative to placebo continued without evidence of rebound. Event rates after discontinuation from study for total NMSCs (DFMO 0.236 NMSC/person/year, placebo 0.297, P = 0.48) or the subtypes of basal cell carcinomas (BCC; DFMO 0.179 BCC/person/year, placebo 0.190, P = 0.77) and squamous cell carcinomas (SCC; DFMO 0.057 SCC/person/year, placebo 0.107, P = 0.43) are listed. Follow-up data revealed a persistent but insignificant reduction in new NMSCs occurring in DFMO subjects without evidence of latent or cumulative toxicity relative to placebo subjects. Cancer Prev Res; 5(12); 1368-74. (c) 2012 AACR.