Diona Damian, MBBS, PhD
For those with a history of non-melanoma skin cancer (NMSC), reducing their risk of recurrence can be as simple as taking the vitamin B3 pill nicotinamide, according to findings of a phase III trial conducted by researchers in Australia, where the disease affects more than half the population over their lifetime.
The study found that the risk of new NMSC in study participants who took a 500-mg nicotinamide tablet twice daily was reduced by 23% compared with placebo.
“This is an affordable chemoprevention strategy which can be instantly translated into clinical practice,” said senior study author and professor of Dermatology Diona Damian, MBBS, PhD, who presented the findings on behalf of her colleagues at the University of Sydney at a presscast held in advance of the 2015 ASCO Annual Meeting.
Basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are the most common skin cancers among fair-skinned populations. In the United States, an estimated 5 million people are treated for NMSC every year at a cost of $4.8 billion. The incidence is rising worldwide as the population ages, despite intensive campaigns stressing the importance of sun protection.
Ultraviolet (UV) radiation damages DNA in skin cells and triggers suppression of skin immunity, Damian explained, and given the impact of BCC and SCC, “We were looking for something that could counter these UV pathways to skin cancer.” She added that over 10 years of research, “we’ve shown that nicotinamide actively provides skin cells with an energy boost after UV exposure which results in enhanced rates of DNA repair and restoration of skin immunity.”
Building on previous phase II studies demonstrating that nicotinamide reduced precancerous actinic keratoses (AKs) in heavily sun-damaged Australian patients, the research team designed a phase III, double-blind, randomized controlled trial involving 386 patients who had at least two prior skin cancers in the past 5 years (mean = 8; range 2-52); approximately two-thirds of the participants were men, and the median age was 66 (range, 30-91 years). Many of the patients had ongoing medical issues, such as heart disease, arthritis, high blood pressure, and chronic lung disease.
“This was a ‘warts-and-all’ population, the sort of people that we treat every day in the clinic,” said Damian.
Participants were randomized 1:1 to receive twice-daily nicotinamide or placebo for 12 months; thorough skin checks were performed every 3 months by a dermatologist, and new skin cancers were confirmed on biopsy. The estimated relative rate reduction (RRR) in new NMSC was 0.23 (95% CI, 0.04-0.38; P = .02) in patients who received the vitamin); treatment effects were comparable for both BCC (RRR = 0.20; 95% CI, -0.06 to 0.39; P = .1) and SCC (RRR = 0.30; 95%, 0-0.51; P = .05).
“Interestingly, this reduction in skin cancers seemed to start at the first 3-month visit,” said Damian. “However, when people stopped taking the vitamin after 12 months, the benefit was no longer seen.”
Researchers also looked at the number of AKs, the study’s secondary endpoint, and nicotinamide also reduced these by approximately 15%, said Damian, even in a very sun-damaged group, who had an average 15 keratoses per person at baseline.
Damian stressed that it is only the B3 formulation of nicotinamide which can be recommended and not niacin (nicotinic acid) formulations which can be more toxic (eg, headaches, flushing, low blood pressure).
“Nicotinamide was very well tolerated. There was no difference in adverse events or blood parameters in the two arms,” she continued. She said nicotinamide also does not pose problems with drug interactions, which is particularly beneficial for older patients who are often prescribed multiple medications.
Damian said that based on these results, nicotinamide, “is ready to move straight into the clinic,” for those “who already have a skin cancer track record,” adding, however, “it is not something that we recommend at this stage for the general population.”
Further studies are planned to determine if the vitamin can help reduce skin cancers in individuals with suppressed immune systems, who have skin cancer rates 50 times higher than those with normal immune systems. “With this study, we have a remarkably simple and inexpensive way to help people avoid repeat diagnoses of some of the most common skin cancers.
"With just a daily vitamin pill, along with sun protection and regular skin cancer screenings, people at high risk for these types of skin cancers have a good preventive plan to follow,” said ASCO president Peter Paul Yu, MD, FACP, FASCO.
Martin AJ, Chen A, Choy B, et al. Oral nicotinamide to reduce actinic cancer: a phase III double-blind randomized controlled trial. J Clin Oncol. 2015;(suppl; abstr 9000).
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