A Phase 3 Randomized Trial of Nicotinamide for Skin-Cancer Chemoprevention.

Phase 3 randomized placebo-controlled trial in adults at high risk for nonmelanoma skin cancer, defined by having had at least two histologically confirmed nonmelanoma skin cancers in the prior five years. The study was conducted in Sydney, Australia, at Royal Prince Alfred Hospital and Westmead Hospital, with enrollment from July 2, 2012 to June 14, 2014. In the nicotinamide arm, 193 participants were randomized and 191 were analyzed.

Oral nicotinamide 500 mg tablets twice daily for 12 months, compared with placebo. The active product was Insolar (Blackmores).

Oral nicotinamide was safe and reduced new nonmelanoma skin cancers and actinic keratoses during the 12-month treatment period, but the benefit was not maintained after treatment stopped. In the nicotinamide group, the mean number of new nonmelanoma skin cancers was 1.8 per person versus 2.4 with placebo, a 23% lower rate after adjustment for center and 5-year skin-cancer history (95% CI, 4 to 38; P = 0.02). Basal-cell carcinomas were 20% lower (95% CI, -6 to 39; P = 0.12), and squamous-cell carcinomas were 30% lower (95% CI, 0 to 51; P = 0.05). Actinic keratoses were also reduced at 3, 6, 9, and 12 months, with no clinically significant between-group differences in adverse events.

The main benefit was limited to the active treatment period and was not maintained after stopping nicotinamide. Follow-up was only 12 months, and the population was a selected high-risk group from two centers in Sydney, which may limit generalizability. There was also a baseline imbalance in asthma history between groups.