Issues & Insights:
Non-Melanoma Skin Cancer Prevention: A Place for Nicotinamide?

Issue 26 Winter/Spring 2016

Each year approximately 4.3 million adults in the United States are treated for non-melanoma skin cancer (NMSC), more than twice the number treated for all other types of cancer combined.

Among Americans aged 65 years or older, roughly 7 percent of men and 5 percent of women receive treatment annually for NMSCs, of which about 80 percent are basal cell carcinomas and 20 percent are squamouscell carcinomas.

Fortunately, NMSC is only rarely fatal, and early diagnosis with outpatient treatment usually produces a good cosmetic and medical outcome. However, NMSC care comes at a cost that already approaches 5 billion dollars annually and is increasing by approximately 15% per year.1

mole on woman's back is examined

The risk of developing NMSC is extremely high in some rare, inherited conditions (eg, basal cell nevus syndrome, xeroderma pigmentosum), and the risk is also increased to a lesser extent by exposure to arsenic, ionizing radiation, and immunosuppressive therapy.

The vast majority of cases, however, are attributable to chronic UV light exposure among individuals with relatively low levels of skin pigment, especially those with blond or red hair and skin that tends to burn rather than tan after being in the sun.

The U.S. Surgeon General’s “Call to Action to Prevent Skin Cancer” issued in 2014 thus emphasized sun protection and avoiding indoor tanning devices as ways to address the rising impact of NMSC (as well as melanoma).2

NMSC typically arises in older adults following decades of sunlight exposure, and many patients with a new NMSC have already had one or more skin cancers treated in the past. Therefore, while targeting UV light exposure is a rational long-term prevention strategy for the entire population, investigators have been seeking other approaches to reduce NMSC over the shorter term among higher-risk patients.

Potential preventive interventions involving retinol (vitamin A), retinoids (synthetic derivatives of retinol), betacarotene, and selenium, have all been evaluated in clinical trials, but the results have been disappointing or inconclusive. Moreover, the toxicity of some of these agents would make them unsuitable for many patients.

With this as background, the recent preliminary report of the ONTRAC trial, a study that evaluated nicotinamide for preventing NMSC, could be especially important.

Nicotinamide is sometimes referred to as “niacinamide”, and like niacin it is a form of vitamin B3. Unlike niacin, however, nicotinamide does not cause vascular symptoms, such as flushing, when taken at relatively high oral doses. It is also readily available at low cost without prescription.

Previous clinical studies suggested that nicotinamide could prevent actinic keratoses – precursors of squamous cell carcinoma – and in laboratory studies nicotinamide was shown to promote repair of DNA damage in skin cells. Nicotinamide, applied to the skin or taken by mouth, has also been found to have anti-inflammatory effects in patients with acne and other skin conditions.

A team from Australia presented the ONTRAC trial in abbreviated form at the May 2015 meeting of the American Society for Clinical Oncology. It was conducted at two referral centers in Sydney and involved almost 400 adult patients, averaging 66 years of age, who had been treated within the past 5 years for 2 or more NMSCs.

close up, hand holds bottle of pills

The investigators assigned participants at random to take 500 mg of nicotinamide or a placebo pill twice daily for one year. Only 1 in 10 participants discontinued their pills before the end of the trial period, and virtually all had at least one follow-up skin evaluation following randomization.

Over the 12 months of the study, participants treated with nicotinamide were diagnosed with an average of 1.8 new NMSCs each – 27 percent fewer than the average of 2.4 each for those who were given placebo, a difference that the investigators reported as statistically significant. The reduction in NMSC risk applied to both basal cell and squamous cell carcinomas, the researchers noted.

The results of this trial raise the intriguing possibility that NMSC can be prevented effectively and rapidly through a simple, inexpensive strategy of taking nicotinamide pills at a dose that seems to cause no symptoms or harmful side-effects.

However, patients who have had NMSC should consider several factors before deciding whether to start taking nicotinamide on their own.

Firstly, the reduction in NMSC risk may not be large enough to justify a major change in their lifestyle or dermatological care; they would still need to avoid sunlight exposure and have regular follow-up skin examinations.

Secondly, the results of the trial are based on only 12 months of follow-up, so we don’t yet know whether the reported benefit will persist over time, diminish, or increase.

Lastly, although the Australian investigators used a randomized, double-blind approach that reduces the possibility of erroneous results, clinical trials of skin cancer prevention pose daunting challenges in their conduct and statistical analysis that will need to be explored more extensively in subsequent reports from this and other trials.

In summary, new findings for nicotinamide offer promise of a practical way to reduce the huge clinical and economic burden due to skin cancer. However, more detailed information and longer follow-up results from this trial, as well as data from subsequent investigations, are needed before nicotinamide can be confidently recommended for preventing NMSC.

References:

  1. Guy JP Jr, Machlin SR,Ekwueme DU, Yabroff KR. Prevalence and Costs of Skin Cancer Treatment in the U.S., 2002_2006 and 2007_2011. Am J Prev Med 2015;48(2):183–187)
  2. U.S. Department of Health and Human Services. The Surgeon General’s Call to Action to Prevent Skin Cancer. Washington, DC: U.S. Dept of Health and Human Services, Office of the Surgeon General; 2014. http://www.surgeongeneral.gov.