Nicotinamide for Skin-Cancer Chemoprevention in Transplant Recipients.

Abstract

BACKGROUND:

Immunosuppressed organ-transplant recipients have an increased incidence of, and mortality from, skin cancer. Nicotinamide (vitamin B3) enhances the repair of ultraviolet (UV) radiation-induced DNA damage, reduces the cutaneous immunosuppressive effects of UV radiation, and reduces the incidence of keratinocyte 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.

METHODS:

In this phase 3 trial, we randomly assigned, in a 1:1 ratio, organ-transplant recipients who had had at least two keratinocyte cancers in the past 5 years to receive 500 mg of nicotinamide or placebo twice daily for 12 months. Participants were examined for skin lesions by dermatologists at 3-month intervals for 12 months. The primary end point was the number of new keratinocyte cancers during the 12-month intervention period. Secondary end points included the numbers of squamous-cell and basal-cell carcinomas during the 12-month intervention period, the number of actinic keratoses until 6 months after randomization, safety, and quality of life.

RESULTS:

A total of 158 participants were enrolled, with 79 assigned to the nicotinamide group and 79 to the placebo group. The trial was stopped early owing to poor recruitment. At 12 months, there were 207 new keratinocyte cancers in the nicotinamide group and 210 in the placebo group (rate ratio, 1.0; 95% confidence interval, 0.8 to 1.3; P = 0.96). No significant between-group differences in squamous-cell and basal-cell carcinoma counts, actinic keratosis counts, or quality-of-life scores were observed. Adverse events and changes in blood or urine laboratory variables were similar in the two groups.

CONCLUSIONS:

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. (Funded by the National Health and Medical Research Council; ONTRANS Australian New Zealand Clinical Trials Registry number, ACTRN12617000599370.).

• Authors: Nicholas C Allen, Andrew J Martin, Victoria A Snaidr, Renee Eggins, Alvin H Chong, Pablo Fernandéz-Peñas, Douglas Gin, Shireen Sidhu, Vanessa L Paddon, Leith A Banney, Adrian Lim, Edward Upjohn, Helmut Schaider, Aparna D Ganhewa, Jennifer Nguyen, Catriona A McKenzie, Saurabh Prakash, Catriona McLean, Alistair Lochhead, Jan Ibbetson, Andrew Dettrick, Anthony Landgren, Katherine J Allnutt, Clare Allison, Rachael B Davenport, Blake P Mumford, Brittany Wong, Brendan Stagg, Alexander Tedman, Hannah Gribbin, Harrison A Edwards, Nicholas De Rosa, Thomas Stewart, Brent J Doolan, Yonatan Kok, Kate Simpson, Zhi M Low, Tom Kovitwanichkanont, Richard A Scolyer, Haryana M Dhillon, Janette L Vardy, Steven J Chadban, David G Bowen, Andrew C Chen, Diona L Damian
• Journal: The New England journal of medicine (N Engl J Med) Vol. 388 Issue 9 Pg. 804-812 (Mar 02 2023) ISSN: 1533-4406 [Electronic] United States
• PMID: 36856616 (Publication Type: Clinical Trial, Phase III, Journal Article, Randomized Controlled Trial)
• Copyright: Copyright © 2023 Massachusetts Medical Society.

Chemical References

• Niacinamide
• Antineoplastic Agents

Topics

• Humans
• Australia
• Carcinoma, Basal Cell (etiology, prevention & control)
• Carcinoma, Squamous Cell (etiology, prevention & control)
• Chemoprevention
• Keratosis, Actinic (etiology, prevention & control)
• Niacinamide (administration & dosage, therapeutic use)
• Quality of Life
• Skin Neoplasms (etiology, prevention & control)
• Transplant Recipients
• Immunocompromised Host
• Organ Transplantation (adverse effects)
• Antineoplastic Agents (administration & dosage, therapeutic use)
• Ultraviolet Rays (adverse effects)