Twelve months of twice-daily oral doses of nicotinamide, a form of vitamin B3, may reduce the incidence of new nonmelanoma skin cancers in patients at high risk for skin cancer, according to the results of a large, randomized, controlled, double-blind, Phase III trial.
“Nicotinamide is widely accessible as an inexpensive over-the-counter vitamin supplement and presents a new chemopreventive opportunity against nonmelanoma skin cancers that is readily translatable into clinical practice,” said senior author Diona Damian, MBBS, PhD, Professor of Dermatology at the University of Sydney in Australia.
“This is the first clear evidence that we can reduce skin cancers using a simple vitamin, together with sensible sun protection,” she stated. “However, people at high risk of skin cancer will still need regular check-ups with their doctor.”
Nicotinamide enhances DNA repair and prevents cutaneous immune suppression after ultraviolet radiation exposure. The vitamin supplement has been shown to reduce photocarcinogenesis in mice and human nonmelanoma skin cancers in Phase II clinical trials.
The Oral Nicotinamide to Reduce Actinic Cancer (ONTRAC) study was conducted in 2 tertiary treatment centers in Sydney, Australia, from 2012 to 2014. In the study, 386 patients, mean age 66 years, who had at least 2 nonmelanoma skin cancers in the previous 5 years (therefore considered to be at high risk) were randomly assigned to 500 mg nicotinamide twice daily or placebo for 12 months. The study population reflected the mix of patients typically seen in a skin cancer clinic. About two-thirds of the patients were men. The patients had a mean of 8 nonmelanoma skin cancers in the previous 5 years.
“The average nonmelanoma skin cancer rate was significantly lower for the nicotinamide group (1.77) than the placebo group (2.42),” said Dr Damian. The estimated relative reduction in nonmelanoma skin cancer was 23%, adjusting for center and history.
Nicotinamide had comparable efficacy in preventing the most common types of nonmelanoma skin cancers, basal cell carcinoma, and squamous cell carcinoma.
The numbers of actinic keratoses were reduced in the nicotinamide group by 11% at 3 months and by 20% at 9 months of treatment.
There were no clinically relevant differences in adverse event rates between the 2 groups.
The ONTRAC study builds on a decade of preclinical and early clinical studies that suggested that nicotinamide both enhances the repair of DNA in skin cells damaged by sunlight and protects the skin’s immune system against UV light, Dr Damian said.
Cells convert nicotinamide into nicotinamide adenine dinucleotide, which is essential for cellular energy production. The researchers suggest that nicotinamide helps replenish cellular energy after sunlight exposure, giving cells the energy boost they need to repair DNA damage and prevent immune suppression.
Further studies are planned to determine whether nicotinamide can help reduce skin cancers in persons who have suppressed immune systems, such as organ transplant recipients who need to take lifelong immune suppressive medications. Rates of skin cancer are up to 50 times higher in persons who have suppressed immune systems than in those who have normal immune systems.
The researchers presented their results at the American Society of Clinical Oncology annual meeting in Chicago.