一项烟酰胺用于皮肤癌化学预防的 3 期随机试验。

A Phase 3 Randomized Trial of Nicotinamide for Skin-Cancer Chemoprevention.

机构信息

From the Department of Dermatology and Bosch Institute (A.C.C., R.A.D., G.M.H., D.L.D.) and the Department of Tissue Pathology and Diagnostic Oncology (C.A.M., R.A.S.), University of Sydney at Royal Prince Alfred Hospital, National Health and Medical Research Council Clinical Trials Center (A.J.M.), Central Clinical School (A.C.C., R.A.S., G.M.H., D.L.D.) and Concord Clinical School (J.L.V.), Sydney Medical School, Center for Medical Psychology and Evidence-Based Decision-Making (H.M.D., J.L.V.), and Sydney School of Public Health (A.K.), University of Sydney, Melanoma Institute Australia, North Sydney (R.A.S., D.L.D.), the Department of Dermatology, University of Sydney at Westmead Hospital (B.C., P.F.-P., G.S.G., N.C.), and Concord Repatriation General Hospital (J.L.V.) - all in Sydney.

出版信息

N Engl J Med. 2015 Oct 22;373(17):1618-26. doi: 10.1056/NEJMoa1506197.

DOI:10.1056/NEJMoa1506197

PMID:26488693

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.).

摘要

背景

非黑色素瘤皮肤癌，如基底细胞癌和鳞状细胞癌，是常见的癌症，主要由紫外线（UV）辐射引起。烟酰胺（维生素 B3）已被证明具有预防紫外线辐射引起的损伤的作用，并降低新的光化性角化病的发生率。

方法

在这项 3 期、双盲、随机、对照试验中，我们以 1:1 的比例将 386 名在过去 5 年内至少有 2 次非黑色素瘤皮肤癌的参与者随机分配，每天接受 500 毫克烟酰胺 2 次或安慰剂，持续 12 个月。参与者在 18 个月内每 3 个月由皮肤科医生评估一次。主要终点是在 12 个月的干预期间新发生的非黑色素瘤皮肤癌（即基底细胞癌加鳞状细胞癌）的数量。次要终点包括新发生的鳞状细胞癌和基底细胞癌的数量、12 个月干预期间光化性角化病的数量、6 个月干预后非黑色素瘤皮肤癌的数量以及烟酰胺的安全性。

结果

在 12 个月时，烟酰胺组新发生非黑色素瘤皮肤癌的比率比安慰剂组低 23%（95%置信区间[CI]，4 至 38）（P=0.02）。烟酰胺组和安慰剂组在新发生的基底细胞癌（烟酰胺组低 20%[95%CI，-6 至 39]，P=0.12）和新发生的鳞状细胞癌（烟酰胺组低 30%[95%CI，0 至 51]，P=0.05）方面也发现了类似的差异。烟酰胺组在 3 个月时的光化性角化病数量比安慰剂组低 11%（P=0.01），在 6 个月时低 14%（P<0.001），在 9 个月时低 20%（P<0.001），在 12 个月时低 13%（P=0.001）。在 12 个月的干预期间，两组之间在不良事件的数量或类型方面没有发现显著差异，而且在停止使用烟酰胺后也没有证据表明有获益。