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.).
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
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
Cites
A systematic review of worldwide incidence of nonmelanoma skin cancer
Lomas, A., Leonardi‐Bee, J., & Bath-Hextall, F. J. (2012) · British Journal of Dermatology · doi:10.1111/j.1365-2133.2012.10830.x · Cited by 1,943
The epidemiology of UV induced skin cancer
Armstrong, B. K., & Kricker, A. (2001) · Journal of Photochemistry and Photobiology B: Biology · doi:10.1016/s1011-1344(01)00198-1 · Cited by 1,811
Self-citationCutaneous Squamous-Cell Carcinoma
Alam, M., & Ratner, D. (2001) · New England Journal of Medicine · doi:10.1056/nejm200103293441306 · Cited by 1,311
Green, A., Williams, G., Nèale, R., Hart, V., Leslie, D., Parsons, P., Marks, G. C., Gaffney, P., Battistutta, D., Frost, C., et al. (1999) · The Lancet · doi:10.1016/s0140-6736(98)12168-2 · Cited by 976
Prevalence and Costs of Skin Cancer Treatment in the U.S., 2002−2006 and 2007−2011
Guy, G. P., Machlin, S. R., Ekwueme, D. U., & Yabroff, K. R. (2014) · American Journal of Preventive Medicine · doi:10.1016/j.amepre.2014.08.036 · Cited by 871
Reduced melanoma after regular sunscreen use: randomized trial follow-up
Green, A. C., Williams, G. M., Logan, V., & Strutton, G. M. (2011) · Journal of Clinical Oncology · doi:10.1200/jco.2010.28.7078 · Cited by 799
Reduction of Solar Keratoses by Regular Sunscreen Use
Thompson, S., Jolley, D., & Marks, R. (1993) · New England Journal of Medicine · doi:10.1056/nejm199310143291602 · Cited by 782
Rubin, A. I., Chen, E. H., & Ratner, D. (2005) · New England Journal of Medicine · doi:10.1056/nejmra044151 · Cited by 772
Prevention of Skin Cancer in Xeroderma Pigmentosum with the Use of Oral Isotretinoin
Kraemer, K. H., DiGiovanna, J. J., Moshell, A. N., Tarone, R. E., & Peck, G. L. (1988) · New England Journal of Medicine · doi:10.1056/nejm198806233182501 · Cited by 574
Safety of high-dose nicotinamide: a review
Knip, M., Douek, I. F., Moore, W. P. T., Gillmor, H. A., McLean, A. E. M., Bingley, P. J., & Gale, E. A. M. (2000) · Diabetologia · doi:10.1007/s001250051536 · Cited by 423
Bavinck, J. N. B., Tieben, L. M., van der Woude, F. J., TEGZESS, A. M., Hermans, J., ter Schegget, J., & Vermeer, B. J. (1995) · Journal of Clinical Oncology · doi:10.1200/jco.1995.13.8.1933 · Cited by 395
Yarosh, D., Klein, J., O'Connor, A., Hawk, J., Rafal, E., & Wolf, P. (2001) · The Lancet · doi:10.1016/s0140-6736(00)04214-8 · Cited by 390
Tanno, O., Ota, Y., Kitamura, N., Katsube, T., & Inoue, S. (2000) · British Journal of Dermatology · doi:10.1111/j.1365-2133.2000.03705.x · Cited by 266
Bastiaens, M. T., Hoefnagel, J. J., Vermeer, B. J., Bavinck, J. N. B., BRUIJN, J. A., & Westendorp, R. G. J. (1998) · Journal of Investigative Dermatology · doi:10.1046/j.1523-1747.1998.00217.x · Cited by 256
Elmets, C. A., Viner, J. L., Pentland, A. P., Cantrell, W., Lin, H., Bailey, H. H., Kang, S., Linden, K. G., Heffernan, M. P., Duvic, M. A., et al. (2010) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/djq442 · Cited by 239
Liu, D., Pitta, M., Jiang, H., Lee, J.-H., Zhang, G., Chen, X., Kawamoto, E. M., & Mattson, M. P. (2013) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2012.11.020 · Cited by 238
Non‐melanoma skin cancer in Australia
Fransen, M., Karahalios, A., Sharma, N., English, D. R., Giles, G. G., & Sinclair, R. D. (2012) · The Medical Journal of Australia · doi:10.5694/mja12.10654 · Cited by 221
UV Radiation-Induced Immunosuppression Is Greater in Men and Prevented by Topical Nicotinamide
Damian, D. L., Patterson, C. R. S., Stapelberg, M., Park, J., Barnetson, R. S., & Halliday, G. M. (2007) · Journal of Investigative Dermatology · doi:10.1038/sj.jid.5701058 · Cited by 204
Self-citationMoon, T. E., Levine, N. S., Cartmel, B., Bangert, J. L., Rodney, S., Dong, Q., Peng, Y. M., & Alberts, D. S. (1997) · PubMed · Cited by 199
Acitretin for chemoprevention of non‐melanoma skin cancers in renal transplant recipients
George, R., Weightman, W., Russ, G. R., Bannister, K. M., & Mathew, T. H. (2002) · Australasian Journal of Dermatology · doi:10.1046/j.1440-0960.2002.00613.x · Cited by 186
McKenna, & Murphy (1999) · British Journal of Dermatology · doi:10.1046/j.1365-2133.1999.02765.x · Cited by 173
Oral nicotinamide reduces actinic keratoses in phase II double-blinded randomized controlled trials.
Surjana, D., Halliday, G., Martin, A., Moloney, F., & Damian, D. (2012) · Journal of Investigative Dermatology · doi:10.1038/jid.2011.459 · Cited by 142
Self-citationSurjana, D., Halliday, G. M., & Damian, D. L. (2013) · Carcinogenesis · doi:10.1093/carcin/bgt017 · Cited by 138
Self-citationOral nicotinamide protects against ultraviolet radiation-induced immunosuppression in humans
Yiasemides, E., Sivapirabu, G., Halliday, G. M., Park, J., & Damian, D. L. (2008) · Carcinogenesis · doi:10.1093/carcin/bgn248 · Cited by 134
Self-citationNicotinamide Prevents Ultraviolet Radiation‐induced Cellular Energy Loss
Park, J., Halliday, G. M., Surjana, D., & Damian, D. L. (2010) · Photochemistry and Photobiology · doi:10.1111/j.1751-1097.2010.00746.x · Cited by 125
Self-citationIsmail, F., Mitchell, L., Casabonne, D., Gulati, A., Newton, R., Proby, C. M., & Harwood, C. A. (2006) · British Journal of Dermatology · doi:10.1111/j.1365-2133.2006.07454.x · Cited by 114
Chen, A. C., & Damian, D. L. (2014) · Australasian Journal of Dermatology · doi:10.1111/ajd.12163 · Cited by 98
Self-citationKuchel, J. M., Barnetson, R. S., & Halliday, G. M. (2005) · Photochemical & Photobiological Sciences · doi:10.1039/b504068j · Cited by 79
Self-citationTreatment of Cutaneous Neoplasia with Etretinate in Renal Transplant Recipients
Shuttleworth, D., Marks, R., Griffin, P., & Salaman, J. R. (1988) · QJM · doi:10.1093/oxfordjournals.qjmed.a068237 · Cited by 72
Nicotinamide enhances repair of ultraviolet radiation‐induced DNA damage in primary melanocytes
Thompson, B. C., Surjana, D., Halliday, G. M., & Damian, D. L. (2014) · Experimental Dermatology · doi:10.1111/exd.12430 · Cited by 65
Self-citationDNA repair, immunosuppression, and skin cancer.
Gupta, A. K., & Lynch, L. E. (2004) · PubMed · Cited by 65
Statin use is not associated with reduced risk of skin cancer: a meta-analysis
Li, X., Wu, X., & Chen, Q. (2013) · British Journal of Cancer · doi:10.1038/bjc.2013.762 · Cited by 47
Systemic retinoids for chemoprevention of non-melanoma skin cancer in high-risk patients.
Marquez, C. B., Bair, S., Smithberger, E., Cherpelis, B. S., & Glass, L. F. (2010) · PubMed · Cited by 46
Niacin or niacinamide? Nicotinic acid or nicotinamide? What is the difference?
Ranchoff, R. E., & Tomecki, K. J. (1986) · Journal of the American Academy of Dermatology · doi:10.1016/s0190-9622(86)80149-9 · Cited by 26
Pietkiewicz, P., Gornowicz‐Porowska, J., Bowszyc‐Dmochowska, M., Jagielska, J., Helak-Łapaj, C., Kaczmarek, E., & Dmochowski, M. (2014) · Clinical and Experimental Dermatology · doi:10.1111/ced.12355 · Cited by 18
Liu, D., PITTA, M. G. R., Jiang, H., Lee, J. H., Zhang, G., Chen, X., Kawamoto, E. M., & Mattson, M. P. (2013) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2013.03.017 · Cited by 17
McKenzie, P., & Weldon, P. R. (2015) · doi:10.5040/9781472593450.ch-002 · Cited by 8
Flagged first, then by citations
1 of the 38 references couldn’t be matched to a known paper.
Research works printed but not linked: 4
- Yarosh DB, 2004, Cutis, 74, 10
- Moon TE, 1997, Cancer Epidemiol Biomarkers Prev, 6, 949
- Marquez C, 2010, J Drugs Dermatol, 9, 753
- Shuttleworth D, 1988, Q J Med, 68, 717
Cited by
Sorted by citations
Hallmarks of aging: An expanding universe
López-Otín, C., Blasco, M. A., Partridge, L., Serrano, M., & Kroemer, G. (2023) · Cell · doi:10.1016/j.cell.2022.11.001 · Cited by 6,549
NAD+ in Brain Aging and Neurodegenerative Disorders
Lautrup, S., Sinclair, D. A., Mattson, M. P., & Fang, E. F. (2019) · Cell Metabolism · doi:10.1016/j.cmet.2019.09.001 · Cited by 790
“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 (Chen et al., 2015).”
Madeo, F., Carmona-Gutierrez, D., Hofer, S. J., & Kroemer, G. (2019) · Cell Metabolism · doi:10.1016/j.cmet.2019.01.018 · Cited by 630
Burstein, H. J., Krilov, L., Aragon‐Ching, J. B., Baxter, N. N., Chiorean, E. G., Chow, W. A., Groot, J. F. D., Devine, S. M., DuBois, S. G., El‐Deiry, W. S., et al. (2017) · Journal of Clinical Oncology · doi:10.1200/jco.2016.71.5292 · Cited by 603
Guidelines of care for the management of cutaneous squamous cell carcinoma
Alam, M., Armstrong, A. W., Baum, C. L., Bordeaux, J. S., Brown, M. D., BUSAM, K. J., Eisen, D. B., Iyengar, V., LOBER, C. W., Margolis, D. J., et al. (2018) · Journal of the American Academy of Dermatology · doi:10.1016/j.jaad.2017.10.007 · Cited by 600
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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
