烟酰胺用于预防移植受者的皮肤癌。

Nicotinamide for Skin-Cancer Chemoprevention in Transplant Recipients.

机构信息

From the Department of Dermatology, University of Sydney at Royal Prince Alfred Hospital (N.C.A., V.A.S., A.D.G., A.C.C., D.L.D.), the NHMRC (National Health and Medical Research Council) Clinical Trials Centre, University of Sydney (A.J.M., R.E.), and the Department of Renal Medicine (S.J.C.) and the A.W. Morrow Gastroenterology and Liver Centre (D.G.B.), Royal Prince Alfred Hospital, Camperdown, NSW, the Skin Health Institute, Carlton, VIC (A.H.C., K.J.A., R.B.D., B.P.M., T.K.), the Department of Dermatology, University of Sydney at Westmead Hospital, Westmead, NSW (P.F.-P.), the Department of Dermatology, the Alfred Hospital (D.G., A.D.G., J.N.), the Department of Anatomical Pathology, Alfred Health (C.M.), and the Department of Anatomical Pathology, Royal Melbourne Hospital (A. Landgren), Melbourne, VIC, the Department of Dermatology, Royal Adelaide Hospital (S.S., C.A., B.W., B.S.), and South Australia Pathology (J.I.), Adelaide, SA, the Department of Dermatology, University of New South Wales at St. Vincent's Hospital (V.L.P., N.D.R., T.S.), NSW Health Pathology (C.A.M., R.A.S.), the Department of Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital (C.A.M., R.A.S.), Faculty of Medicine and Health (R.A.S., J.L.V., D.G.B.), Melanoma Institute Australia (R.A.S., D.L.D.), Charles Perkins Centre (R.A.S., S.J.C.), and the Centre for Medical Psychology and Evidence-Based Decision-Making (H.M.D., J.L.V.), University of Sydney, and the Liver Immunology Program, the Centenary Institute, University of Sydney and Royal Prince Alfred Hospital (D.G.B.), Sydney, the Departments of Dermatology (L.A.B., H.S., A.D., A.T., H.G., H.A.E.) and Pathology (A.D.), Sunshine Coast University Hospital, Griffith University Medical School (L.A.B.), and the School of Health and Behavioural Sciences, University of the Sunshine Coast (A.D.), Birtinya, QLD, the Department of Dermatology, University of Sydney at Royal North Shore Hospital, St. Leonards, NSW (A. Lim), the Department of Dermatology, Royal Melbourne Hospital, Parkville, VIC (E.U., B.J.D., Y.K., K.S., Z.M.L.), the Dermatology Research Centre, Diamantina Institute, the University of Queensland (H.S., H.A.E.), and the Department of Dermatology, Princess Alexandra Hospital (H.A.E.), Woolloongabba, QLD, Melbourne Pathology, Sonic Healthcare, Collingwood, VIC (S.P.), Southern.IML Pathology, Sonic Healthcare, Coniston, NSW (A. Lochhead), Wollongong Hospital, Wollongong, NSW (A. Lochhead), the School of Medicine, University of Queensland, Herston (A.T.), and the Department of Medicine, Concord Clinical School, University of Sydney, and Concord Cancer Centre, Concord Repatriation General Hospital, Concord, NSW (J.L.V.) - all in Australia.

出版信息

N Engl J Med. 2023 Mar 2;388(9):804-812. doi: 10.1056/NEJMoa2203086.

DOI:10.1056/NEJMoa2203086

PMID:36856616

Abstract

BACKGROUND

Immunosuppressed organ-transplant recipients have an increased incidence of, and mortality from, skin cancer. Nicotinamide (vitamin B) enhances the repair of ultraviolet (UV) radiation-induced DNA damage, reduces the cutaneous immunosuppressive effects of UV radiation, and reduces the incidence of keratinocyte cancers (including squamous-cell and basal-cell carcinomas) and actinic keratoses among high-risk immunocompetent patients. Whether oral nicotinamide is useful for skin-cancer chemoprevention in organ-transplant recipients is unclear.

METHODS

In this phase 3 trial, we randomly assigned, in a 1:1 ratio, organ-transplant recipients who had had at least two keratinocyte cancers in the past 5 years to receive 500 mg of nicotinamide or placebo twice daily for 12 months. Participants were examined for skin lesions by dermatologists at 3-month intervals for 12 months. The primary end point was the number of new keratinocyte cancers during the 12-month intervention period. Secondary end points included the numbers of squamous-cell and basal-cell carcinomas during the 12-month intervention period, the number of actinic keratoses until 6 months after randomization, safety, and quality of life.

RESULTS

A total of 158 participants were enrolled, with 79 assigned to the nicotinamide group and 79 to the placebo group. The trial was stopped early owing to poor recruitment. At 12 months, there were 207 new keratinocyte cancers in the nicotinamide group and 210 in the placebo group (rate ratio, 1.0; 95% confidence interval, 0.8 to 1.3; P = 0.96). No significant between-group differences in squamous-cell and basal-cell carcinoma counts, actinic keratosis counts, or quality-of-life scores were observed. Adverse events and changes in blood or urine laboratory variables were similar in the two groups.

CONCLUSIONS

In this 12-month, placebo-controlled trial, oral nicotinamide therapy did not lead to lower numbers of keratinocyte cancers or actinic keratoses in immunosuppressed solid-organ transplant recipients. (Funded by the National Health and Medical Research Council; ONTRANS Australian New Zealand Clinical Trials Registry number, ACTRN12617000599370.).

摘要

背景

接受免疫抑制治疗的器官移植受者皮肤癌的发病率和死亡率增加。烟酰胺（维生素 B）可增强紫外线（UV）辐射诱导的 DNA 损伤修复，降低 UV 辐射对皮肤的免疫抑制作用，并降低高危免疫功能正常患者的角质形成细胞癌（包括鳞状细胞癌和基底细胞癌）和光化性角化病的发生率。口服烟酰胺是否对器官移植受者的皮肤癌化学预防有用尚不清楚。

方法

在这项 3 期临床试验中，我们以 1:1 的比例随机分配过去 5 年内至少发生过 2 次角质形成细胞癌的器官移植受者，每天服用 500mg 烟酰胺或安慰剂，持续 12 个月。在 12 个月的干预期间，每 3 个月由皮肤科医生检查一次皮肤病变。主要终点是 12 个月干预期间新发角质形成细胞癌的数量。次要终点包括 12 个月干预期间鳞状细胞癌和基底细胞癌的数量、随机分组后 6 个月前光化性角化病的数量、安全性和生活质量。

结果

共纳入 158 名参与者，其中 79 名分配至烟酰胺组，79 名分配至安慰剂组。由于招募情况不佳，试验提前终止。12 个月时，烟酰胺组有 207 例新发角质形成细胞癌，安慰剂组有 210 例（发生率比，1.0；95%置信区间，0.8 至 1.3；P=0.96）。两组间鳞状细胞癌和基底细胞癌计数、光化性角化病计数或生活质量评分无显著差异。两组的不良事件和血液或尿液实验室变量的变化相似。