[ASCO2015]口服维生素B3可降低非黑色素瘤皮肤癌风险

发布时间:2015-05-14 浏览次数:677次 来源: 作者:

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第51届美国临床肿瘤学会(ASCO)年会将于5月29日-6月2日在芝加哥召开。13日,ASCO发表了四项重要研究,分别为广泛使用维生素片可减少非黑色素瘤皮肤癌风险,早期化疗可延长晚期前列腺癌患者生命,以及可以提高罕见肾癌儿童和复发性多发性骨髓瘤成人预后的新治疗方案。医脉通整理如下:


口服维生素降低常见,非黑色素瘤皮肤癌风险(摘要号,9000)


澳大利亚ONTRAC试验表明,每天服用两片烟酰胺(维生素B3家族的一种),可将皮肤癌高风险人群患非黑色素瘤皮肤癌风险降低23%。


在大多数国家,烟酰胺是一种安全,廉价,并可用的非处方药。研究结果有可能减少皮肤癌(全球浅肤色的人群中最常见的一种癌症)的健康负担和经济成本。


“这是第一次有明确的证据表明,使用一种简单的维生素加上合理的防晒就可以减少皮肤癌。我们希望这些发现可以立即转化为临床实践,”悉尼大学皮肤病学教授,高级研究员Diona Damian教授说。“然而,高危皮肤癌人群仍然需要定期接受医生检查。”


非黑色素瘤皮肤癌发病的主要原因是阳光照射。尽管有很多宣传防晒的运动,但皮肤癌的发病率在全世界仍在继续增加。美国每年大约有五百万人接受非黑色素瘤皮肤癌治疗,在澳大利亚约为一百万人。一半以上的人口在其一生中有可能患非黑色素瘤皮肤癌。


在这项研究中,386名患者在过去五年中至少患有两个非黑色素瘤皮肤癌,因此被认为是高危人群,他们被随机分配为口服12个月烟酰胺组(每日服用),或安慰剂对照组。这项研究入组患者代表皮肤专科常见的皮肤癌患者——平均年龄是66岁,三分之二的患者是男性(皮肤癌在男性更常见)。很多患者有基础疾病,如心脏病,关节炎,高血压,慢性肺病。


与对照组相比,烟酰胺组患者新的皮肤癌发病率下降23%。烟酰胺组在三个月治疗后,恶变角质(厚的,增生鳞状皮肤,可能导致癌症发生)减少了11%,在九个月的治疗后减少了20%。同时,值得注意的是,烟碱酸是维生素B3一个不同形式,可导致的不良反应包括头痛,皮肤潮红,和低血压,而烟酰胺并没有上述不良反应,亦无任何严重的不良反应。


最常见的非黑色素瘤皮肤癌的病理类型为基底细胞皮肤癌(BCC)和鳞状细胞皮肤癌(SCC)。SCC可以发生淋巴结和内部器官转移。BCC很少发生转移,但会导致面部整型问题,因为它们经常出现在脸部。烟酰胺在预防BCC和SCC发病上有类似的功效。


阳光下紫外线辐射致癌通过两个关键路径——DNA损伤和抑制皮肤免疫力(皮肤的免疫系统可以帮助清除癌症发病之前的异常细胞)。本项研究建立在前十年的早期临床前和临床研究基础上,表明烟酰胺可提高经日照受损皮肤细胞的DNA修复功能,保护皮肤的免疫系统以对抗紫外线。


DNA修复是一个需要消耗大量能量的过程。紫外线辐射可阻碍皮肤细胞的能量在生成。在皮肤细胞内,烟碱可转化为烟酰胺腺嘌呤二核苷酸,其对细胞能量的生成是至关重要的。研究人员认为,烟酰胺可帮助补充阳光照射后细胞能量,给予细胞所需的能量,增加DNA损伤修复功能,以防止细胞免疫受抑制。


烟酰胺是否可以帮助降低免疫系统功能不全患者的皮肤癌发病率,仍需进一步研究,例如器官移植受者必须终身服用免疫抑制药物。免疫系统功能不全的患者和免疫功能正常的人群相比,皮肤癌发病率提高了50倍。


本研究由澳大利亚国家卫生和医学研究委员会(NHMRC)提供资金支持。


摘要原文:


Background: Nicotinamide (vitamin B3) enhances DNA repair and prevents cutaneous immune suppression after ultraviolet (UV) radiation exposure. It reduces photocarcinogenesis in mice, and human non-melanoma skin cancers (NMSC) in Phase 2 clinical trials. We report the outcomes of the Phase 3 Oral Nicotinamide to Reduce Actinic Cancer (ONTRAC) Study.


Methods: ONTRAC was a double-blind RCT conducted in two tertiary treatment centers in Sydney, Australia from 2012-2014. 386 immune competent participants with ≥ 2 histologically-confirmed NMSC in the past 5 years were randomized (1:1) to oral nicotinamide 500mg bd (NIC) or matched placebo (PBO) for 12 months. The primary endpoint was the number of new NMSCs to 12 months. Secondary endpoints included number of squamous cell carcinomas (SCCs), basal cell carcinomas (BCCs), and actinic keratoses (AKs) to 12 months. Skin reviews by dermatologists were performed 3 monthly. The sample size provided 90% power to detect a 33% difference in NMSC rates. Analysis was by intention-to-treat.


Results: The mean age of study population was 66 years, the mean number of NMSC in the past 5 years was 8, and 63% were men. Treatment discontinuation rates were 9% for PBO versus 10% for NIC. 99% of patients underwent at least one post-baseline skin assessment. The average NMSC rate was significantly lower for NIC (1.77) than PBO (2.42). The estimated relative rate reduction (RRR) was 0.23 (95% CI: 0.04 to 0.38, p = 0.02) adjusting for center and NMSC history, and 0.27 (95% CI: 0.05 to 0.44; p = 0.02) with no adjustment. Treatment effects of comparable magnitude were found for both BCCs (RRR = 0.20, 95% CI: -0.06 to 0.39, p = 0.1) and SCCs (RRR = 0.30, 95% CI: 0 to 0.51, p = 0.05). AK counts were reduced for NIC compared to PBO by 11% at 3 months (p = 0.01), 14% at 6 months (p < 0.001), 20% at 9 months (p < 0.0001) and 13% at 12 months (p < 0.005). There were no clinically relevant differences in adverse event rates between the two arms.


Conclusions: Nicotinamide reduces NMSC formation in high risk patients and is well tolerated. Furthermore, it is widely accessible as an inexpensive over-the-counter vitamin supplement and presents a new chemopreventive opportunity against NMSCs that is readily translatable into clinical practice. Clinical trial information: ACTRN12612000625875.


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医脉通编译自:New Cancer Treatment and Prevention Studies Signal Major Advances for Children and Adults,2015 ASCO Annual Meeting,May 13,2015,5:00 PM