Oral nicotinamide significantly reduced the formation of new nonmelanoma skin cancers (NMSCs) compared with placebo in patients with severely sun-damaged skin and was well tolerated, according to results of a new phase III trial (Abstract 9000).
Andrew J. Martin, PhD, of the NHMRC Clinical Trials Centre, University of Sydney, Australia, presented results of the ONTRAC study during the Melanoma/Skin Cancers Oral Abstract Session on Saturday, May 30.
Dr. Andrew James Martin
Nicotinamide is the amide form of vitamin B3. It has no vasodilatory side effects, unlike nicotinic acid. In previous studies, nicotinamide has been shown to enhance DNA repair after UV exposure and reduce UV immunosuppression. In phase II trials conducted by Dr. Martin’s group, it was shown to decrease the formation of actinic keratoses. Nicotinamide is available as a supplement for less than $10 per month.
The double-blind, phase III ONTRAC trial randomly assigned 386 patients to receive either 500 mg of oral nicotinamide twice daily (193 patients) or matched placebo (193 patients) for 12 months. All patients had at least two NMSCs in the past 5 years. The mean age of the study cohort was 66, and the majority of patients (63%) were men. The average number of NMSCs in the past 5 years was just over eight. At baseline, the patients who received the placebo had 46.2 actinic keratoses, and the nicotinamide group had 47.7.
Over the 12 months of the study, patients who received the placebo developed an average of 2.4 new NMSCs, compared with 1.8 in the nicotinamide group. After adjustment for center and NMSC history, this yielded a relative rate reduction (RRR) of 0.23 (95% CI [0.04, 0.38]; p = 0.02).
Specifically for basal cell carcinomas, there was an average of 1.7 new cases for patients who received placebo and 1.3 for patients who received nicotinamide, for an RRR of 0.20 (95% CI [-0.06, 0.39]; p = 0.1). For squamous cell carcinomas, the placebo rate was 0.7 compared with 0.5 in the nicotinamide group, for an RRR of 0.30 (95% CI [0.00, 0.51]; p = 0.05).
The study drug also reduced the incidence of actinic keratoses at various time points. At 3 months, there was a relative reduction of 11% (95% CI [3%, 18%]; p = 0.01), at 6 months, it was 14% (95% CI [7%, 21%]; p = 0.0005), at 9 months it was 20% (95% CI [13%, 27%]; p < 0.0001), and at 12 months it was 13% (95% CI [5%, 20%]; p = 0.001).
For all of the NMSC and keratoses reductions, Martin said there was no effect beyond the 12-month treatment period, suggesting a rebound effect after the drug is stopped. There were no differences between the groups with regard to adverse events.
Discussant Daniel G. Coit, MD, of Memorial Sloan Kettering Cancer Center, said there are still unanswered questions regarding optimal dosing and the effects of longer-term treatment.
He also pointed out that there were, on average, 4.3 million new diagnoses of NMSCs each year from 2007-2011, at an annual cost of $4.75 billion. “If what we’ve heard today is true, and we can reduce that by 25%, we’re going to save a lot of money,” Dr. Coit said. “This is a staggering public health problem.”
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