A Phase 3 Randomized Trial of Nicotinamide for Skin-Cancer Chemoprevention
A Phase 3 Randomized Trial of Nicotinamide for Skin-Cancer Chemoprevention
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DOI：
10.1056/nejmoa1506197
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发表时间：
2015-10-22
影响因子：
158.5
通讯作者：
Damian, Diona L.
中科院分区：
文献类型：
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作者：
Chen, Andrew C.;Martin, Andrew J.;Damian, Diona L.
背景：非黑色素瘤皮肤癌，如基底细胞癌和鳞状细胞癌，是主要由紫外线（UV）辐射引起的常见癌症。烟酰胺（维生素B-3）已被证明对紫外线辐射造成的损害具有保护作用，并可降低新的恶性前光化性角化病的发病率。方法：在这项三期、双盲、随机对照试验中，我们以1:1的比例随机分配386名在过去5年内至少患有2例非黑色素瘤皮肤癌的参与者，每天两次接受500 mg烟酰胺或安慰剂治疗12个月。皮肤科医生每隔3个月对参与者进行评估，持续18个月。主要终点是在12个月的干预期内新发非黑色素瘤皮肤癌（即基底细胞癌加鳞状细胞癌）的数量。次要终点包括12个月干预期间新发鳞状细胞癌和基底细胞癌的数量以及光化性角化病的数量，干预后6个月非黑色素瘤皮肤癌的数量，以及烟酰胺的安全性。结果12个月后，烟酰胺组的非黑色素瘤皮肤癌新发率比安慰剂组低23%(95%可信区间[CI]， 4 ~ 38) （P = 0.02）。烟酰胺组和安慰剂组在新发基底细胞癌（烟酰胺组降低20% [95% CI， -6 ~ 39], P = 0.12）和新发鳞状细胞癌（烟酰胺组降低30% [95% CI， 0 ~ 51], P = 0.05）方面也存在类似差异。烟酰胺组在3个月时光化性角化病的数量比安慰剂组低11% (P = 0.01)， 6个月时低14% （P = 0.01）
BACKGROUNDNonmelanoma skin cancers, such as basal-cell carcinoma and squamous-cell carcinoma, are common cancers that are caused principally by ultraviolet (UV) radiation. Nicotinamide (vitamin B-3) has been shown to have protective effects against damage caused by UV radiation and to reduce the rate of new premalignant actinic keratoses.METHODSIn 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.RESULTSAt 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