Highlights from the Literature 2
Nicotinamide for Skin-Cancer Chemoprevention in Transplant Recipients
By Mariam Mafee, MD, FACMS
In 2015, the ONTRAC trial (Oral Nicotinamide to Reduce Actinic Cancer) demonstrated that nicotinamide 500mg BID could help prevent skin cancer in immunocompetent patients.1 This phase 3 trial in Australia found that there was a 23% lower rate of keratinocyte cancers in those taking nicotinamide compared to placebo. In March 2023, the same group published a follow-up study of nicotinamide use in solid organ transplant recipients (SOTR).
This was a phase 3 trial, where 158 SOTR were randomly assigned 1:1 to receive nicotinamide 500mg BID or placebo BID. Patients had to have at least 2 keratinocyte cancers within the past 5 years, and a transplant at least 12 months prior. Exclusion criteria included: impaired liver or kidney function, genetic skin cancer syndromes, large areas of confluent skin cancer, invasive melanoma or internal cancer within the past 5 years, field treatments for actinic keratoses within the past 4 weeks, and commencement of oral retinoids or mTOR inhibitors within the past 6 months.
Patients were to continue the regimen for 12 months, and adherence was monitored by tablet counts every 6 months. Skin cancer checks were performed at baseline and every 3 months for 12 months by blinded dermatologists. Blood samples were obtained at the same time points to evaluate blood counts, serum electrolyte levels, serum immunosuppressant levels, blood glucose, and renal and liver function.
The primary end point was the number of new keratinocyte cancers (BCC, SCC invasive, or SCC in situ) during the 12-month intervention period. Secondary end points included the numbers of SCC or BCC during the 12-month intervention period, the number of actinic keratoses at 6 months, safety, and quality of life. Of note, the trial was stopped early due to low recruitment numbers within the study timeframe.
The mean number of keratinocyte cancers per participant during the 12-month period was 2.6 in the nicotinamide group and 2.7 in the placebo group, with a rate ratio of 1.0. The mean actinic keratosis count was 13.1 in the nicotinamide group and 12.8 in the placebo group. There were no significant differences in SCC and BCC counts, actinic keratosis counts, or quality-of-life scores.
Adverse events and changes in laboratory variables were similar in the two groups. The most frequent adverse events were infections and infestations (predominantly respiratory, urinary tract, and skin infections). Three systemic cancers were diagnosed in the placebo group and one in the nicotinamide group, and one patient in the placebo group was diagnosed with chronic antibody-mediated rejection of the kidney transplant.
Treating cutaneous malignancies and skin cancer prevention is extremely challenging in the SOTR population. Although it was disappointing that nicotinamide did not decrease the risk of keratinocyte carcinomas or actinic keratoses, it was reassuring that there were minimal side effects in this patient population with a high risk for medication interaction and complications. It is important to note that this study was underpowered relative to the original enrollment goals, limiting the reliability of the conclusions.
References:
- Chen AC, Martin AJ, Choy B, et al. A phase 3 randomized trial of nicotinamide for skin cancer chemoprevention. N Engl J Med 2015;373:1618-26.