Nicotinamide for Skin-Cancer Chemoprevention in Transplant Recipients

Allen, Nicholas; Martin, Andrew; Snaidr, Victoria A.; Eggins, Renee; Chong, Alvin H; Fernández‐Peñas, Pablo; Gin, Douglas L.; Sidhu, Shireen; Paddon, Vanessa L; Banney, Leith; Lim, Adrian; Upjohn, Edward; Schaider, Helmut; Ganhewa, Aparna D; Nguyen, Jennifer; McKenzie, Catriona; Prakash, Saurabh; McLean, Catriona; Lochhead, Alistair; Ibbetson, Jan; Dettrick, Andrew; Landgren, Anthony; Allnutt, Katherine J; Allison, Clare; Davenport, Rachael; Mumford, Blake P; Wong, Brittany; Stagg, Brendan; Tedman, Alexander; Gribbin, Hannah; Edwards, Harrison A.; Rosa, Nicholas De; Stewart, T. D.; Doolan, Brent J; Kok, Yonatan; Simpson, Kate; Low, Zhi M; Kovitwanichkanont, Tom; Scolyer, Richard A.; Dhillon, Haryana M.; Vardy, Janette L.; Chadban, Steven J.; Bowen, David G.; Chen, Andrew C.; Damian, Diona L.

doi:10.1056/nejmoa2203086

Cited by 46 publications

(23 citation statements)

References 31 publications

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“…The main results and features of the selected studies are presented in Table 1 . All the enclosed studies were double-blind, randomized trials carried out in Australia [ 31 , 32 , 33 , 34 ]. Two studies each were Phase II [ 31 , 34 ] and Phase III [ 32 , 33 ].…”

Section: Resultsmentioning

confidence: 99%

“…All the enclosed studies were double-blind, randomized trials carried out in Australia [ 31 , 32 , 33 , 34 ]. Two studies each were Phase II [ 31 , 34 ] and Phase III [ 32 , 33 ]. Three studies reported oral NAM posology of 500 mg twice daily; only in Surjana (2012) did randomized participants receive 500 mg of NAM once or twice daily (data presented in Table 1 are combined).…”

Section: Resultsmentioning

confidence: 99%

“…Three studies reported oral NAM posology of 500 mg twice daily; only in Surjana (2012) did randomized participants receive 500 mg of NAM once or twice daily (data presented in Table 1 are combined). Treatment duration varied from four [ 31 ] to twelve months [ 32 , 33 ]. Participants had at least two histologically confirmed NMSCs in the previous five years.…”

Section: Resultsmentioning

confidence: 99%

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The Role of Nicotinamide as Chemo-Preventive Agent in NMSCs: A Systematic Review and Meta-Analysis

Tosti,

Pepe,

Gnagnarella

et al. 2023

Nutrients

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Background: Nicotinamide is the active form of vitamin B3 (niacin) obtained through endogenous synthesis, mainly through tryptophan metabolism and dietary supplements, fish, meats, grains, and dairy products. It participates in cellular energy metabolism and modulates multiple cellular survival and death pathways. Nicotinamide has been widely studied as a safe chemopreventive agent that reduces actinic keratosis (AKs) and non-melanoma skin cancers (NMSC). Methods: We used the Medline, EMBASE, PubMed, and Cochrane databases to search the concepts “nicotinamide”, “chemoprevention”, and “skin cancer” up to August 2023. Three independent authors screened titles and abstracts for intervention and study design before searching full texts for eligibility criteria. The primary outcome was the impact of oral nicotinamide on the incidence of NMSC in high-risk patients. We also conducted a systematic search to identify relevant epidemiological studies published evaluating dietary niacin intake and the risk of NMSC. Results: Two hundred and twenty-five studies were reviewed, and four met the inclusion criteria. There was no association between NAM consumption and risk for squamous cell carcinoma (SCC) (rate ratio (RR) 0.81, 95% CI 0.48–1.37; I2 = 0%), basal cell carcinoma (BCC) (RR 0.88, 95% CI 0.50–1.55; I2 = 63%), and NMSC (RR 0.82, 95% CI 0.61–1.12; I2 = 63%). Adverse events were rare and acceptable, allowing optimal compliance of patients to the treatment. We found only one article evaluating the association between niacin dietary intake and NMSC risk, supporting a potential beneficial role of niacin intake concerning SCC but not BCC or melanoma. Conclusions: The present meta-analysis shows, by pooling immunocompetent and immunosuppressed patients, that there is insufficient evidence that oral nicotinamide therapy significantly reduces the number of keratinocyte cancers.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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The Role of Nicotinamide as Chemo-Preventive Agent in NMSCs: A Systematic Review and Meta-Analysis

Tosti,

Pepe,

Gnagnarella

et al. 2023

Nutrients

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“…This study could not conclude statistically significant results due to a small sample size (n = 22), although they reported reductions in AKs in the nicotinamide group compared to the placebo group [33]. More recently, given nicotinamide's potential activity against immunosuppression, the Oral Nicotinamide to Reduce Actinic Cancer after Transplant (ONTRANS) trial was conducted on solid-organ transplant recipients with a history of multiple NMSC who received nicotinamide for 12 months [34]. The incidence of NMSC was nearly identical in nicotinamide and placebo groups.…”

Section: Examples Of Chemoprevention Trials 91 Nicotinamidementioning

confidence: 93%

Recent Advances in Clinical Research for Skin Cancer Chemoprevention

Tow,

Hanoun,

Andresen

et al. 2023

Cancers

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Neoplasm arising from the keratinocytes or melanocytes in the skin is the most prevalent type of cancer in the United States and worldwide. Since ultraviolet (UV) radiation may be a causing factor for several types of skin cancer, effective strategies to manage skin cancer include preventive measures such as minimizing exposure to UV and applying sunscreens. However, the effect of sunscreen in reducing skin cancer incidence remains uncertain. An alternative approach to prevent skin cancer is chemoprevention, which is defined as using either natural products or synthetic compounds to inhibit, delay, or reverse the development of cancer. Preclinical studies have demonstrated the effectiveness of multiple pharmacological agents and dietary supplements. However, whether preclinical findings can be translated into clinical application is unknown. This review evaluates the state of recent clinical trials investigating chemopreventive agents focusing on skin cancer to compare the target populations, interventions, endpoints, and outcomes of these trials. The ClinicalTrials and PubMed databases were searched for their available literature using the key words “skin cancer” and “chemoprevention”. The objective of this review is to provide updated information on the effectiveness and side effects of promising chemopreventive agents in human subjects and to identify research gaps.

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“…In a meta-analysis conducted by Mainville et al [ 55 ] in 2022, they concluded that the low cost and over-the-counter accessibility of NAM support its relevance in the tertiary prevention of skin cancers in the immunocompetent population. However, these positive results have not been demonstrated in solid organ transplant recipients; in a 12-month placebo-controlled trial with a total of 158 enrolled participants, oral nicotinamide therapy did not significantly decrease the number of keratinocyte cancers or AK [ 56 ].…”

Section: Other Therapies Used Off-label For Actinic Keratosis and Can...mentioning

confidence: 99%

Topical Immunotherapy for Actinic Keratosis and Field Cancerization

Bernal Masferrer,

Gracia Cazaña,

Bernad Alonso

et al. 2024

Cancers

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This comprehensive review delves into various immunotherapeutic approaches for the management of actinic keratoses (AKs), precancerous skin lesions associated with UV exposure. Although there are treatments whose main mechanism of action is immune modulation, such as imiquimod or diclofenac, other treatments, apart from their main effect on dysplastic cells, exert some immunological action, which in the end contributes to their efficacy. While treatments like 5-fluorouracil, imiquimod, photodynamic therapy, and nicotinamide are promising in the management of AKs, especially in immunocompetent individuals, their efficacy is somewhat reduced in solid organ transplant recipients due to immunosuppression. The analysis extends to optimal combination, focusing on cryoimmunotherapy as the most relevant. New immunotherapies include resimiquimod, ingenol disoxate, N-phosphonacetyl-L-aspartate (PALA), or anti-PD1 that have shown promising results, although more studies are needed in order to standardize their use.

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Nicotinamide for Skin-Cancer Chemoprevention in Transplant Recipients

Cited by 46 publications

References 31 publications

The Role of Nicotinamide as Chemo-Preventive Agent in NMSCs: A Systematic Review and Meta-Analysis

The Role of Nicotinamide as Chemo-Preventive Agent in NMSCs: A Systematic Review and Meta-Analysis

Recent Advances in Clinical Research for Skin Cancer Chemoprevention

Topical Immunotherapy for Actinic Keratosis and Field Cancerization

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