A Phase 3 Randomized Trial of Nicotinamide for Skin-Cancer Chemoprevention.
Level 2 - randomized trial
Phase 3 double-blind randomized controlled trial
PubMed 26488693 · doi:10.1056/NEJMoa1506197
What was done
In a phase 3, double-blind, multicenter randomized controlled trial, 386 participants with a history of at least two nonmelanoma skin cancers in the previous 5 years were randomly assigned (1:1) to receive oral nicotinamide (500 mg twice daily) or placebo for 12 months. Dermatologic evaluations were performed at 3-month intervals for 18 months (12 months on-intervention and 6 months post-intervention). The primary end point was the number of new nonmelanoma skin cancers (basal-cell carcinomas plus squamous-cell carcinomas) during the 12-month intervention period. Secondary end points included counts of each specific skin cancer subtype, actinic keratosis counts, post-intervention skin cancers, and safety.
What was found
At 12 months, the rate of new nonmelanoma skin cancers was 23% lower in the nicotinamide group than in the placebo group (95% CI, 4 to 38; P=0.02). New basal-cell carcinomas were 20% lower (95% CI, -6 to 39; P=0.12) and new squamous-cell carcinomas were 30% lower (95% CI, 0 to 51; P=0.05). Actinic keratoses were reduced in the nicotinamide group by 11% at 3 months (P=0.01), 14% at 6 months (P<0.001), 20% at 9 months (P<0.001), and 13% at 12 months (P=0.001). No noteworthy between-group differences occurred in the number or types of adverse events. No evidence of benefit persisted during the 6-month post-intervention period after nicotinamide was discontinued.
Why it matters
Oral nicotinamide is an effective, well-tolerated chemopreventive agent that reduces the incidence of new nonmelanoma skin cancers and actinic keratoses in high-risk individuals. Because protective effects disappear upon cessation, continuous treatment is required to maintain benefit.
Limits
The study evaluated only high-risk individuals with at least two prior nonmelanoma skin cancers, limiting generalizability to lower-risk populations. The reduction in basal-cell carcinoma alone did not reach statistical significance. The trial tested only a single dosing regimen and followed participants for only 6 months after treatment discontinuation.
Cited by
- supports A clinical study conducted in Australia showed that oral nicotinamide supplementation prevented non-melanoma skin cancer.