The DOI matches its Crossref record; 37 of the 38 references it cites were found in a registry or an index.
A Phase 3 Randomized Trial of Nicotinamide for Skin-Cancer Chemoprevention
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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In the citing paper
“Clinical trials have demonstrated the efficacy of NAD + precursors in the chemoprevention of non-melanoma skin cancer 126 , in reversing insulin resistance in prediabetic women 127 , and in reducing neuroinflammation in patients with Parkinson 's disease 128 .”
From Hallmarks of aging: An expanding universe (2023) · cites this paper as [126]
In the citing paper
“| | Human | NAM in patients with 2 non- melanoma skin cancers in the preceding 5 years (Phase 3 trial) | Reduced rates of new nonmelanoma skin cancers and keratosis | 126 |”
From Hallmarks of aging: An expanding universe (2023) · cites this paper as [126]
In the citing paper
“the clinical data showing NAM is relatively safe (1,000–2,000 mg/day) and is readily absorbed from the gastrointestinal tract with peak serum concentrations in 1 h after oral ingestion”
From NAD+ in Brain Aging and Neurodegenerative Disorders (2019) · cites this paper as Chen et al., 2015
In the citing paper
“in some cases NAD+/NADH and its metabolites can inhibit cancer growth and metastasis”
From NAD+ in Brain Aging and Neurodegenerative Disorders (2019) · cites this paper as Chen et al., 2015
In the citing paper
“A phase-III randomized large clinical trial reported that oral NAM was safe and effective in reducing the rates of new nonmelanoma skin cancers and actinic keratosis in high-risk patients”
From NAD+ in Brain Aging and Neurodegenerative Disorders (2019) · cites this paper as Chen et al., 2015
Citations
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“28 On the other hand, a systematic review found that oral nicotinamide did not play a significant role in preventing nonmelanoma skin cancers; however, it included studies on both immunocompetent and immunocompromised patients.”
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Additional file 1 of Nicotinamide inhibits melanoma in vitro and in vivo
Scatozza, F., Moschella, F., D’Arcangelo, D., Rossi, S., Tabolacci, C., Giampietri, C., Proietti, E., Facchiano, F., & Facchiano, A. (2020) · Figshare · doi:10.6084/m9.figshare.13064299
Additional file 2 of Nicotinamide inhibits melanoma in vitro and in vivo
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“Chemoprevention: The ONTRAC Phase III RCT supports nicotinamide 500 mg BID to reduce new NMSC events during treatment in high-risk populations—an attractive, low-cost option for irradiated survivors, with the caveat that benefits wane after discontinuation [101,124–126].”
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Metadata
- 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
- 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
- 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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