Neurocognitive Function and Quality of Life Outcomes in the ONTRAC Study for Skin Cancer Chemoprevention by Nicotinamide

Martin, Andrew; Dhillon, Haryana M.; Vardy, Janette; Dalziell, Robyn; Choy, Bonita; Fernández‐Peñas, Pablo; Dixon, Ann; Renton, Corrinne; George, Gayathri St; Chinniah, Niranthari; Halliday, Gary M.; Damian, Diona L.

doi:10.3390/geriatrics4010031

Cited by 5 publications

(12 citation statements)

References 19 publications

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“…In addition, NAM reduced the incidence of AK and NMSC at significant levels; both BCC and SCC were reduced compared to the placebo group [55]. As part of the ONTRAC trial, oral NAM-treated patients showed no significant effect on their neurocognitive function or life outcome [95].…”

Section: Skinmentioning

confidence: 94%

The Role of Nicotinamide in Cancer Chemoprevention and Therapy

2020

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Nicotinamide (NAM) is a water-soluble form of Vitamin B3 (niacin) and a precursor of nicotinamide-adenine dinucleotide (NAD+) which regulates cellular energy metabolism. Except for its role in the production of adenosine triphosphate (ATP), NAD+ acts as a substrate for several enzymes including sirtuin 1 (SIRT1) and poly ADP-ribose polymerase 1 (PARP1). Notably, NAM is an inhibitor of both SIRT1 and PARP1. Accumulating evidence suggests that NAM plays a role in cancer prevention and therapy. Phase III clinical trials have confirmed its clinical efficacy for non-melanoma skin cancer chemoprevention or as an adjunct to radiotherapy against head and neck, laryngeal, and urinary bladder cancers. Evidence for other cancers has mostly been collected through preclinical research and, in its majority, is not yet evidence-based. NAM has potential as a safe, well-tolerated, and cost-effective agent to be used in cancer chemoprevention and therapy. However, more preclinical studies and clinical trials are needed to fully unravel its value.

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Section: Skinmentioning

confidence: 94%

The Role of Nicotinamide in Cancer Chemoprevention and Therapy

2020

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“…However, there is no evidence of benefit after NAM is discontinued [88]. Any significant effects of oral NAM on cognitive function nor on quality of life have been found [90].…”

Section: Nad+ Status and Skin Cancermentioning

confidence: 99%

Role of Nicotinamide in Genomic Stability and Skin Cancer Chemoprevention

Fania

Mazzanti

Campione

et al. 2019

IJMS

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Nicotinamide (NAM) is an amide form of vitamin B3 and the precursor of nicotinamide adenine dinucleotide (NAD+), an essential co-enzyme of redox reactions for adenosine triphosphate (ATP) production and for other metabolic processes. As NAD+ status is critical in maintaining cellular energy, vitamin B3 deficiency mainly affects tissues that need high cellular energy causing pellagra and skin sun sensitivity. In animal models, NAD+ deficiency leads to UV sensitivity of the skin, impairs DNA damage response, and increases genomic instability and cancer incidence. Furthermore, NAD+ depletion is associated with human skin aging and cancer. NAM prevents the UV-induced ATP depletion boosting cellular energy and enhances DNA repair activity in vitro and in vivo. Moreover, NAM reduces skin cancer incidence and prevents the immune-suppressive effects of UV in mice. Thus, NAM is involved in the maintenance of genomic stability and may have beneficial effects against skin aging changes and tumor development. Clinical studies showed that topical use of NAM reduces cutaneous aging. Furthermore, oral NAM administration reduces the level of UV-mediated immunosuppression and lowers the rate of non-melanoma skin cancers in high-risk patients. Therefore, NAM replenishment strategy may be a promising approach for skin cancer chemoprevention.

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“…Oral administration of NAM significantly reduced the incidence of actinic keratoses (AK) in high-risk individuals compared to placebo [27] . Furthermore, NAM has notably expressed clinical value in a 2015 phase III randomized trial of NAM by Chen et al, commonly referred to in the literature as the ONTRAC trial [28] . This trial was conducted in a cohort of 386 subjects labeled as high-risk patients due to the inclusion criterion of having at least 2 NMSCs in the previous five years [28] .…”

Section: Nicotinamide Trialsmentioning

confidence: 99%

“…Furthermore, NAM has notably expressed clinical value in a 2015 phase III randomized trial of NAM by Chen et al, commonly referred to in the literature as the ONTRAC trial [28] . This trial was conducted in a cohort of 386 subjects labeled as high-risk patients due to the inclusion criterion of having at least 2 NMSCs in the previous five years [28] . Those given 500 mg of nicotinamide twice daily for twelve months had the rate of new NMSCs decline by 23% compared to the placebo group [28] .…”

Section: Nicotinamide Trialsmentioning

confidence: 99%

“…This trial was conducted in a cohort of 386 subjects labeled as high-risk patients due to the inclusion criterion of having at least 2 NMSCs in the previous five years [28] . Those given 500 mg of nicotinamide twice daily for twelve months had the rate of new NMSCs decline by 23% compared to the placebo group [28] . Specifically, the new BCC rate decreased by 20%, the new SCC rate decreased by 30%, and actinic keratoses decreased by 11% [28] .…”

Section: Nicotinamide Trialsmentioning

confidence: 99%

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An update on clinical trials for chemoprevention of human skin cancer

2023

J Cancer Metastasis Treat

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The pathophysiology of skin cancer is complex, with multiple factors contributing to its development. The proactive treatment of skin cancer has been investigated in the form of chemoprevention of cutaneous malignancies in clinical trials. Chemoprevention is the use of natural or pharmacologic agents that prevent or reverse skin cancer development. Multiple trials have arisen over the past decades to explore the efficacy of specific agents to halt the progression of UV radiation damage. This comprehensive review article aims to assess clinical trials performed with chemopreventive agents for melanoma and nonmelanoma skin cancers. The following compounds were most often used in these trials: nicotinamide, retinoids, polyphenolic antioxidants, COX-2 selective inhibitors, nonsteroidal anti-inflammatory drugs, difluoromethylornithine, and 5-fluorouracil. Many agents show promise in their ability to prevent nonmelanoma skin cancer formation, with few melanoma trials demonstrating efficacy. The chemoprevention efforts aimed at skin cancer are complex; current and future trials will be instrumental in identifying therapeutic agents that pose efficacy in halting cancer development and assessing whether long-term administration is tolerable.

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Neurocognitive Function and Quality of Life Outcomes in the ONTRAC Study for Skin Cancer Chemoprevention by Nicotinamide

Cited by 5 publications

References 19 publications

The Role of Nicotinamide in Cancer Chemoprevention and Therapy

The Role of Nicotinamide in Cancer Chemoprevention and Therapy

Role of Nicotinamide in Genomic Stability and Skin Cancer Chemoprevention

An update on clinical trials for chemoprevention of human skin cancer

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