In an Australian phase III trial (ONTRANS) reported in The New England Journal of Medicine, Allen et al found that 1 year of treatment with nicotinamide (vitamin B3) vs placebo did not reduce the risk of keratinocyte cancers or actinic keratoses in immunosuppressed solid organ transplant recipients.
As stated by the investigators, “Immunosuppressed organ transplant recipients have an increased incidence of, and mortality from, skin cancer. Nicotinamide enhances the repair of ultraviolet (UV) radiation–induced DNA damage, reduces the cutaneous immunosuppressive effects of UV radiation, and reduces the incidence of keratinocytes cancers (including squamous cell and basal cell carcinomas) and actinic keratoses among high-risk immunocompetent patients. Whether oral nicotinamide is useful for skin cancer chemoprevention in organ transplant recipients is unclear.”
Study Details
In the double-blind multicenter trial, 158 organ transplant recipients with two or more keratinocyte cancers in the past 5 years were randomly assigned between May 2017 and August 2019 to receive nicotinamide at 500 mg (n = 179) or placebo (n = 179) twice daily for 12 months. Enrollment was stopped early due to slow recruitment. Patients were examined by dermatologists every 3 months. The primary endpoint was number of new keratinocyte cancers during the 12-month intervention period.
Key Findings
At 12 months, there were 207 new keratinocyte cancers in the nicotinamide group and 210 in the placebo group (rate ratio [RR] = 1.0, 95% confidence interval [CI] = 0.8–1.3, P = .96). The mean number of new keratinocyte cancers per patient was 2.6 vs 2.7.
At 12 months, there were 69 vs 59 new basal cell carcinomas (RR = 1.4, 95% CI = 0.8–2.3) and 138 vs 151 squamous cell carcinomas (RR = 0.9, 95% CI = 0.6–1.2).
A baseline count and at least one postbaseline count of actinic keratoses were available for 153 patients. The mean count of actinic keratoses over the trial, as estimated from a repeated measures model, was 13.1 in the nicotinamide group vs 12.8 in the placebo group (difference = 0.4, 95% CI = −3.0 to 3.7).
Adverse events and changes in blood and urine laboratory variables were similar in the two groups.
The investigators concluded, “In this 12-month, placebo-controlled trial, oral nicotinamide therapy did not lead to lower numbers of keratinocyte cancers or actinic keratoses in immunosuppressed solid organ transplant recipients.”
Diona L. Damian, PhD, of the Department of Dermatology, University of Sydney at Royal Prince Alfred Hospital, is the corresponding author for The New England Journal of Medicine article.
Disclosure: The study was funded by the National Health and Medical Research Council. For full disclosures of the study authors, visit nejm.org.
