Cited by 648Nonmelanoma Skin Cancer StudiesSkin Protection and AgingHead and Neck Cancer Studies

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A Phase 3 Randomized Trial of Nicotinamide for Skin-Cancer Chemoprevention

Chen, Andrew C., Martin, Andrew J., Choy, Bonita, Fernández-Peñas, Pablo, Dalziell, Robyn A., McKenzie, Catriona A., Scolyer, Richard A., Dhillon, Haryana M., Vardy, Janette L., Kricker, Anne, St. George, Gayathri, Chinniah, Niranthari, Halliday, Gary M., Damian, Diona L.·2015·New England Journal of Medicine

DOI 10.1056/nejmoa1506197

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Abstract

BACKGROUND: Nonmelanoma skin cancers, such as basal-cell carcinoma and squamous-cell carcinoma, are common cancers that are caused principally by ultraviolet (UV) radiation. Nicotinamide (vitamin B3) has been shown to have protective effects against damage caused by UV radiation and to reduce the rate of new premalignant actinic keratoses. METHODS: In this phase 3, double-blind, randomized, controlled trial, we randomly assigned, in a 1:1 ratio, 386 participants who had had at least two nonmelanoma skin cancers in the previous 5 years to receive 500 mg of nicotinamide twice daily or placebo for 12 months. Participants were evaluated by dermatologists at 3-month intervals for 18 months. The primary end point was the number of new nonmelanoma skin cancers (i.e., basal-cell carcinomas plus squamous-cell carcinomas) during the 12-month intervention period. Secondary end points included the number of new squamous-cell carcinomas and basal-cell carcinomas and the number of actinic keratoses during the 12-month intervention period, the number of nonmelanoma skin cancers in the 6-month postintervention period, and the safety of nicotinamide. RESULTS: At 12 months, the rate of new nonmelanoma skin cancers was lower by 23% (95% confidence interval [CI], 4 to 38) in the nicotinamide group than in the placebo group (P=0.02). Similar differences were found between the nicotinamide group and the placebo group with respect to new basal-cell carcinomas (20% [95% CI, -6 to 39] lower rate with nicotinamide, P=0.12) and new squamous-cell carcinomas (30% [95% CI, 0 to 51] lower rate, P=0.05). The number of actinic keratoses was 11% lower in the nicotinamide group than in the placebo group at 3 months (P=0.01), 14% lower at 6 months (P<0.001), 20% lower at 9 months (P<0.001), and 13% lower at 12 months (P=0.001). No noteworthy between-group differences were found with respect to the number or types of adverse events during the 12-month intervention period, and there was no evidence of benefit after nicotinamide was discontinued. CONCLUSIONS: Oral nicotinamide was safe and effective in reducing the rates of new nonmelanoma skin cancers and actinic keratoses in high-risk patients. (Funded by the National Health and Medical Research Council; ONTRAC Australian New Zealand Clinical Trials Registry number, ACTRN12612000625875.).

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Authors: Chen, A. C., Martin, A. J., Choy, B., Fernández-Peñas, P., Dalziell, R. A., McKenzie, C. A., Scolyer, R. A., Dhillon, H. M., Vardy, J. L., Kricker, A., St. George, G., Chinniah, N., Halliday, G. M., & Damian, D. L.
Affiliations: The University of Sydney (AU)
ORCID: Chen, Andrew C.
Martin, Andrew J.
McKenzie, Catriona A.
Scolyer, Richard A.
Dhillon, Haryana M.
Vardy, Janette L.
Kricker, Anne
Halliday, Gary M.
Damian, Diona L.
Venue: New England Journal of Medicine
Publisher: Massachusetts Medical Society
Published: 2015-10-22
Volume: 373
Issue: 17
Pages: 1618-1626
ISSN: 0028-4793 (ISSN-L)
1533-4406
DOI: 10.1056/nejmoa1506197
OpenAlex: W1852538637
Cited by: 648
References: 38
Citations by year: 2026: 53 · 2025: 66 · 2024: 59 · 2023: 74 · 2022: 61 · 2021: 75 · 2020: 55 · 2019: 57 · 2018: 49 · 2017: 51 · 2016: 38 · 2015: 4
FWCI: 37.14
Type: journal article
Language: en
Open access: closed
Locations: New England Journal of Medicine (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Dermatology › Nonmelanoma Skin Cancer Studies
Health Sciences › Medicine › Dermatology › Skin Protection and Aging
Health Sciences › Medicine › Otorhinolaryngology › Head and Neck Cancer Studies
Keywords: nicotinamide, nicotinic acid, skin cancer chemoprevention, non-melanoma skin cancer, basal cell carcinoma, squamous cell carcinoma, actinic keratosis, ultraviolet radiation, UV-induced DNA damage, NADPH oxidase, NADPH oxidase inhibitors, adverse events, drug safety, recurrence prevention, long-term follow-up
MeSH terms: Adult, Aged, Aged, 80 and over, Basal Cell Carcinoma, Carcinoma, Basal Cell, Carcinoma, Squamous Cell, Double-Blind Method, Female, Humans, Male, Middle Aged, Niacinamide, Skin Neoplasms, Vitamin B Complex, Secondary Prevention, Keratosis, Actinic

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A Phase 3 Randomized Trial of Nicotinamide for Skin-Cancer Chemoprevention

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