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Nicotinamide, a form of vitamin B3 available without prescription, has been shown in various studies to mitigate some of the deleterious effects of ultraviolet (UV) radiation. The mechanism of action occurs through stopping UV-related ATP depletion and glycolytic blockade. Australian investigators performed a randomized, placebo-controlled trial of oral nicotinamide (500 mg twice daily) in high-risk skin cancer patients (those with at least 2 nonmelanoma skin cancers [NMSCs] in the previous 5 years).
The primary endpoint was the number of new NMSCs (squamous cell and basal cell carcinomas [SCCs and BCCs]), that developed during the treatment period (12 months). They also assessed the number of new actinic keratosis during the treatment period, the number of new NMSCs in the 6 months after treatment, and drug-related adverse effects. The rate of all new NMSCs was 23% lower in nicotinamide recipients than placebo recipients at 12 months, a statistically significant decrease. Individual rates of SCCs, BCCs, and actinic keratosis also decreased, but benefits subsided when treatment ended. Adverse effect rates were similar in nicotinamide and placebo recipients.
Chen AC et al. A phase 3 randomized trial of nicotinamide for skin-cancer chemoprevention. N Engl J Med 2015 Oct 22; 373:1618. (http://dx.doi.org/10.1056/NEJMoa1506197)
Comment
This is an encouraging study using the relatively safe and simple agent nicotinamide for skin cancer prevention. The authors have previously reported a beneficial effect of nicotinamide in reducing actinic keratosis (J Invest Dermatol 2012; 132:1497). It is interesting to note that NMSCs, especially SCCs, were reduced while on treatment but increased in the nicotinamide group after the trial ceased. The reason for the SCC rebound is unclear. Perhaps the cancers were suppressed but not eradicated and subsequently returned to their normal progression after treatment ended. These results are reminiscent of effects of other oral suppressive therapies, such as retinol, acitretin, and isotretinoin, which come with greater side effects than the 1000-mg nicotinamide per day given here.