Two daily doses of nicotinamide, a form of vitamin B3, significantly reduced the occurrence of nonmelanoma skin cancers by 23% in individuals considered at high risk for these lesions in an Australian study. Results of the phase III ONTRAC trial, which will be presented at the 2015 ASCO Annual Meeting,¹ were revealed at a press briefing ahead of the conference.

“This is the first clear evidence that we can reduce skin cancers using a simple vitamin, together with sensible sun protection,” said senior author Diona Damian, MBBS, PhD, Professor of Dermatology at the Dermatology University of Sydney, Australia. The study’s first author was Andrew James Martin, MD, of the NHMRC Clinical Trials Centre at the University of Sydney.

“It’s safe, obscenely inexpensive—less than $10 a month—and it is ready to go straight to the clinic,” Dr. Damian commented in the press briefing. She suggested nicotinamide be offered to individuals who have already had skin cancer.

Major Advance

Peter Paul Yu, MD, FACP, FASCO, President of ASCO and Director of Cancer Research at the Palo Alto Medical Foundation in California, commented at the press briefing, “This is a very exciting prevention trial. We all clamor for preventing, rather than treating, disease, and this is a major advance for us.”

The incidence of skin cancer is increasing worldwide, despite intensive sun protection campaigns. In the United States, 5 million people are treated for nonmelanoma skin cancer each year. The most common types of nonmelanoma skin cancer are basal cell carcinoma and squamous cell carcinoma. In ONTRAC, nicotinamide was equally effective in preventing both these common cancers.

Nicotinamide is believed to work by reducing “photocarcinogenesis.” Ultraviolet radiation in sunlight causes skin cancer through two key pathways: by damaging DNA and by suppressing the immunity that normally eradicates abnormal cells. Nicotinamide both enhances the repair of DNA in damaged skin cells and protects the skin’s immune system against ultraviolet light, presumably by replenishing cellular energy after sunlight, she explained.

ONTRAC Details

The phase III Oral Nicotinamide to Reduce Actinic Cancer (ONTRAC) trial involved 386 Australian adults (mean age, 66 years; 63% male) who had been treated for two or more nonmelanoma skin cancers in the past 5 years (mean number, 8), thus rendering them a high-risk population.

They were randomly assigned to oral nicotinamide (500 mg twice daily) or placebo for 12 months. The primary endpoint was the number of new nonmelanoma skin cancers at 12 months. Secondary endpoints included the number of squamous cell carcinomas, basal cell carcinomas, and actinic keratoses. Dermatologists examined the patients’ skin every 3 months.

The average number of skin cancers per year of the study was significantly lower for the nicotinamide group (1.77) than the placebo group (2.42). The estimated relative rate reduction was 0.23 (P = .02), adjusted for treatment center and patient skin cancer history, and 0.27 (P = .02) with no adjustment, the study found.

“Nicotinamide reduced the incidence of new nonmelanoma skin cancers by 23%,” Dr. Damian reported. “And [the effect] seemed to start as early as the first 3-month visit. When patients stopped after 12 months, benefit was no longer seen.”

This observation was based on two skin examinations performed during the 6 months post-treatment. “All the skin cancer numbers returned to normal; the nicotinamide and placebo numbers were not different. The benefit wears off fairly quickly when you stop taking it. This rebound is similar to what we see with retinoids, which are often prescribed for patients with very large numbers of skin cancers,” she indicated.

The magnitude of benefit in preventing lesions was comparable for basal cell carcinomas and squamous cell carcinomas. Actinic keratosis counts were also reduced in the nicotinamide arm, by 11% at 3 months (P = .01), 14% at 6 months (P < .001), 20% at 9 months (P < .0001), and 13% at 12 months (P < .005).

There were no clinically relevant differences in adverse events between the arms, and treatment discontinuation rates were similar: 10% for nicotinamide and 9% for placebo. Dr. Damian emphasized that nicotinamide should not be confused with nicotinic acid (niacin), another form of vitamin B that produces flushing and other side effects.

The authors plan to study nicotinamide in immunosuppressed persons, whose skin cancer rates are up to 50 times higher than immunocompetent persons. ■

Disclosure: Drs. Damian, Martin, and Yu reported no potential conflicts of interest. For full author disclosures, visit asco.abstracts.org.

Reference

1. Martin AJ, et al: 2015 ASCO Annual Meeting. Abstract 9000. To be presented May 30, 2015.