Dr. Ron’s Research Review – February 6, 2019

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This week’s research review focuses on nicotinamide for Actinic keratosis

Participants were randomized to apply 1% nicotinamide or vehicle twice daily. Primary endpoints were AK count at 3 and 6 months compared with baseline. Of 41 patients screened, four developed skin cancers before commencement, five failed to attend and two were ineligible. The remaining 26 men and four women were randomized to receive nicotinamide (n = 13) or vehicle (n = 17). Two men (vehicle) discontinued at 3 months (one developed melanoma, one liver failure). A basal cell carcinoma (BCC) occurred in one nicotinamide-treated patient and three SCCs, three BCCs and a melanoma were identified in four vehicle-treated patients. At 3 months there was a 10.0 ± 12.0% reduction in AKs with vehicle (P = 0.3) compared with 21.8 ± 10.0% with nicotinamide (P = 0.04; Fig. 1). This difference was not maintained at 6 months (reduction from baseline 22.4 ± 9.6%, P = 0.06 with vehicle; 24.6 ± 15.4% with nicotin- amide, P = 0.1). No site-specific differences were seen. In men, there was a 1.0 ± 13.0% reduction in AKs with vehicle (n = 14, P = 0.8) and a reduction of 17.7 ± 9.5% with nicotinamide (n = 12, P < 0.05) at 3 months. This difference was less marked at 6 months (10.4 ± 9.2%, n = 12, P = 0.4; and 19.5 ± 15.1%, n = 12, P = 0.1 with vehicle and nicotinamide, respectively).  This study found a more rapid rate of AK resolution with nicotinamide compared with vehicle in a group of heavily sun-damaged individuals. (Moloney et al., 2010)
Healthy, immune-competent volunteers with >4 palpable AKs (face, scalp and upper limbs) were recruited. Participants were randomly assigned (1:1) to take nicotinamide 500 mg (Nature’s Own, Virginia, Queensland, Australia) or matched placebo twice daily (Study 1) or once daily (Study 2) for 4 months. At baseline, 2 and 4 months, palp- able AKs were identified visually and by touch by a blinded observer (DS), counted and documented on a body grid chart. At baseline and 2 months, full blood count, creatinine, and liver function were assessed. A total of 35 patients were enrolled in Study 1. One withdrew (nicotinamide) at 2 months because of invasive squamous cell carcinoma (SCC), but returned for his 4-month AK count. A total of 41 patients were enrolled in Study 2; two withdrew from treatment (placebo) soon after their baseline counts because of nursing-home placement, but agreed to follow up AK counts. Two nicotinamide participants withdrew from follow-up for personal reasons soon after enrolment. A 35% relative reduction in AK count at 4 months (95% confidence interval (CI): 18–48%; P 1⁄4 0.0006) was estimated from Study 1 (with similar results at 2 months). A 29% relative reduction in AK count at 4 months (95% CI: 11–44%; P 1⁄4 0.005) was estimated from Study 2 (with smaller but significant differences observed at 2 months). The results of these phase II studies suggest nicotinamide is effective in reducing AKs and shows promise for skin cancer chemoprevention. (Surjana et al., 2012)
Dr. Ron


Articles

 

Randomized, double-blinded, placebo controlled study to assess the effect of topical 1% nicotinamide on actinic keratoses.
(Moloney et al., 2010) Download
Participants were randomized to apply 1% nicotinamide or vehicle twice daily. Primary endpoints were AK count at 3 and 6 months compared with baseline. Of 41 patients screened, four developed skin cancers before commencement, five failed to attend and two were ineligible. The remaining 26 men and four women were randomized to receive nicotinamide (n = 13) or vehicle (n = 17). Two men (vehicle) discontinued at 3 months (one developed melanoma, one liver failure). A basal cell carcinoma (BCC) occurred in one nicotinamide-treated patient and three SCCs, three BCCs and a melanoma were identified in four vehicle-treated patients. At 3 months there was a 10.0 ± 12.0% reduction in AKs with vehicle (P = 0.3) compared with 21.8 ± 10.0% with nicotinamide (P = 0.04; Fig. 1). This difference was not maintained at 6 months (reduction from baseline 22.4 ± 9.6%, P = 0.06 with vehicle; 24.6 ± 15.4% with nicotin- amide, P = 0.1). No site-specific differences were seen. In men, there was a 1.0 ± 13.0% reduction in AKs with vehicle (n = 14, P = 0.8) and a reduction of 17.7 ± 9.5% with nicotinamide (n = 12, P < 0.05) at 3 months. This difference was less marked at 6 months (10.4 ± 9.2%, n = 12, P = 0.4; and 19.5 ± 15.1%, n = 12, P = 0.1 with vehicle and nicotinamide, respectively).  This study found a more rapid rate of AK resolution with nicotinamide compared with vehicle in a group of heavily sun-damaged individuals.

Oral nicotinamide reduces actinic keratoses in phase II double-blinded randomized controlled trials.
(Surjana et al., 2012) Download
Healthy, immune-competent volunteers with >4 palpable AKs (face, scalp and upper limbs) were recruited. Participants were randomly assigned (1:1) to take nicotinamide 500 mg (Nature’s Own, Virginia, Queensland, Australia) or matched placebo twice daily (Study 1) or once daily (Study 2) for 4 months. At baseline, 2 and 4 months, palp- able AKs were identified visually and by touch by a blinded observer (DS), counted and documented on a body grid chart. At baseline and 2 months, full blood count, creatinine, and liver function were assessed. A total of 35 patients were enrolled in Study 1. One withdrew (nicotinamide) at 2 months because of invasive squamous cell carcinoma (SCC), but returned for his 4-month AK count. A total of 41 patients were enrolled in Study 2; two withdrew from treatment (placebo) soon after their baseline counts because of nursing-home placement, but agreed to follow up AK counts. Two nicotinamide participants withdrew from follow-up for personal reasons soon after enrolment. A 35% relative reduction in AK count at 4 months (95% confidence interval (CI): 18–48%; P 1⁄4 0.0006) was estimated from Study 1 (with similar results at 2 months). A 29% relative reduction in AK count at 4 months (95% CI: 11–44%; P 1⁄4 0.005) was estimated from Study 2 (with smaller but significant differences observed at 2 months). The results of these phase II studies suggest nicotinamide is effective in reducing AKs and shows promise for skin cancer chemoprevention.

 

References

Moloney, F, et al. (2010), ‘Randomized, double-blinded, placebo controlled study to assess the effect of topical 1% nicotinamide on actinic keratoses.’, Br J Dermatol, 162 (5), 1138-39. PubMed: 20199551
Surjana, D, et al. (2012), ‘Oral nicotinamide reduces actinic keratoses in phase II double-blinded randomized controlled trials.’, J Invest Dermatol, 132 (5), 1497-500. PubMed: 22297641