A new opportunity for skin cancer prevention may be as near and as simple as taking a vitamin available over-the-counter, according to a large Australian randomized Phase III placebo-controlled trial reported at the American Society of Clinical Oncology Annual Meeting (Abstract 9000).
Oral nicotinamide (vitamin B3) reduced the number of non-melanoma skin cancers and actinic keratoses by 23 percent over a year in high-risk patients with a history of basal cell or squamous cell carcinoma, according to researchers at the University of Sydney.
The data were presented in an ASCO teleconference for reporters in advance of the Annual Meeting.
Diona Damian, MBBS, PhD, Professor of Dermatology at the University of Sydney Medical School, senior author on the study, noted that skin cancer is the most common cancer in fair-skinned populations worldwide, and that the incidence in Australia is four times that of all other cancers combined.
Nicotinamide—which Damian emphasized is not the same as nicotinic acid, a different form of vitamin B3—is safe and affordable, and available over the counter in most countries.
She explained that UV radiation in sunlight causes cancer by damaging DNA in cells, but DNA skin damage from UV radiation also triggers profound suppression of skin immunity. Even low doses of UV radiation profoundly suppress the skin's immune system, she said.
“We were looking for something to counter both of these UV pathways to skin cancer, and we have shown over the past 10 years that nicotinamide—vitamin B3—provides skin cells with an energy boost, resulting in enhanced DNA repair and restoring skin immunity.
“We've also conducted Phase II studies in heavily sun-damaged Australian patients and found that nicotinamide significantly reduced premalignant actinic keratoses in some patients.”
The ONTRAC (Oral Nicotinamide to Reduce Actinic Cancer) study—first author is Andrew James Martin, PhD, Senior Research Fellow at Sydney Medical School—included 386 patients who had at least two skin cancers in the past five years. Median age was 66 years (range of 30 to 91).
The mean number of lesions per patient in the previous five years was eight, with a range of two to 52.
“These were skin cancer super frequent fliers,” Damian said.
Patients were randomized to receive nicotinamide at 500 mg twice daily or placebo for 12 months. Skin reviews were performed by dermatologists every three months, and new cancers were confirmed by biopsy.
The primary endpoint was new non-melanoma skin cancers at 12 months, and the secondary endpoint was premalignant actinic keratoses.
The average skin cancer count at 12 months was 1.77 for nicotinamide versus 2.42 for placebo, a 23 percent reduction, Damian reported, and the effects were comparable for basal cell and squamous cell cancers.
Nicotinamide also reduced the number of actinic keratoses compared with placebo by 11 percent at thee months and by 20 percent at nine months.
Benefits were seen as early as in three months, she said, but there was no effect beyond the treatment period, meaning patients had to continue taking the tablets for them to be effective.
Nicotinamide was well tolerated, Damian said, and there was no difference in adverse events or blood parameters between placebo and nicotinamide. Treatment discontinuation rates were similar: nine percent for patients on placebo and 10 percent for those on nicotinamide.
“It is very important to note that we must distinguish nicotinamide from niacin—nicotinic acid,” Damian said, noting that nicotinamide does not cause headaches, flushing, or low blood pressure as nicotinic acid does.
She said nicotinamide is safe, inexpensive—“less than $10 per month”—and widely available.
“It's almost obscenely inexpensive, and it's already widely commercially available, so this one's ready to go straight into the clinic,” she said.
Instantly in the Clinic
Nicotinamide at this moment is recommended for high-risk patients who have a skin cancer track record, she said.
“We still need the overall skin cancer prevention strategies such as sun screen and regular skin surveillance, especially for high-risk patients, but we now have an additional opportunity for affordable skin cancer chemoprevention that we can instantly translate into clinical practice.”
Damian said future studies are planned to determine if nicotinamide can help reduce skin cancers in patients who are immunosuppressed, who have skin cancer rates 50 times higher than patients with normal immune systems.
“We clamor for preventing rather than treating diseases, and this is a major advance for us,” said ASCO 2014-2015 President Peter Paul Yu, MD, Director of Cancer Research at Palo Alto Medical Foundation.