Alpha-difluoromethylornithine (DFMO), an ornithine decarboxylase inhibitor used in intravenous form to treat African trypanosomiasis and in topical form to treat female hirsutism, was investigated as a chemopreventive agent in patients with prior NMSCs. After a 4-week placebo run-in period, 291 volunteers who took at least 80% of their placebos were randomly assigned to oral DFMO (500 mg/m2 /day) versus placebo for up to 5 years (average 4 years). At baseline, the placebo group had a higher mean number of prior NMSCs than the DFMO group (4.9 vs. 4.2; P = .1), and a longer history of NMSC (P = .002), possibly favoring the DFMO group. The primary endpoint of the study was the number of new NMSC events, and the rate was 0.44 new cancers per year in the DFMO group versus 0.61 in the placebo group (P = .07). In a subset analysis, there was a statistically significant difference in BCC events favoring the DFMO group (0.28 vs. 0.40 per year; P = .03) and no difference in SCC rates. DFMO is known to have ototoxicity, and the average hearing loss of audiograms was greater in the DFMO group, which was about 4 dB versus 2 dB (P = .003). In the DFMO group,10.8% discontinued the study drug because of a greater than 15 dB hearing loss, compared with a 4.5% discontinuation in the placebo group (P = .06). DFMO hearing loss is usually reversible. In summary, the efficacy of DFMO for skin cancer prevention is unclear, and it remains investigational for this indication.
Interventions With Inadequate Evidence as to Whether They Reduce Risk of Melanoma
Results from a collaborative European case-control study and one animal study suggest that sunscreens that protect against sunburn may not protect against UV radiation-associated cutaneous melanoma.[27,28] Nonmodifiable host factors, such as propensity to burn, a large number of benign melanocytic nevi, and atypical nevi may also increase the risk of developing cutaneous melanoma.
A post hoc analysis of the Nambour Skin Cancer Prevention Trial (discussed above) examined the incidence of melanoma at a median of 14.2 person-years of follow-up. In the trial, participants were randomly assigned to daily or discretionary sunscreen use from 1992 to 1996. Follow-up continued until 2006 via either active participation, in which subjects completed periodic questionnaires about new skin cancers and relevant sun behaviors, or passive participation, in which subjects' medical records were reviewed for skin cancer diagnoses; 52% of the trial participants were actively participating as of 2006. Eleven melanomas were diagnosed in the daily sunscreen arm versus 22 in the discretionary-use arm (hazard ratio [HR] = 0.5; 95% CI, 0.24-1.02), of which 3 versus 11 were invasive, respectively (HR = 0.27; 95% CI, 0.08-0.97). There was no difference in the rates of melanoma on prescribed sunscreen application sites between the two groups. This study has several important limitations: melanoma was not a planned outcome of the original trial; the CIs of the outcome estimates are very wide, indicating substantial uncertainty of the magnitude of the effect; and there is potential for the introduction of confounding with the widespread use of the passive participant option during the follow-up phase of the study.