Randomized Double-Blind Placebo-Controlled Trial of Acetyl-L-Carnitine for the Prevention of Taxane-Induced Neuropathy in Women Undergoing Adjuvant Breast Cancer Therapy
Randomized Double-Blind Placebo-Controlled Trial of Acetyl-L-Carnitine for the Prevention of Taxane-Induced Neuropathy in Women Undergoing Adjuvant Breast Cancer Therapy
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DOI：
10.1200/jco.2012.44.8738
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发表时间：
2013-07-10
影响因子：
45.3
通讯作者：
Albain, Kathy S.
中科院分区：
文献类型：
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作者：
Hershman, Dawn L.;Unger, Joseph M.;Albain, Kathy S.
目的化疗引起的周围神经病变（CIPN）是一种常见的疾病，导致治疗效果欠佳。乙酰-L-肉碱（ALC）是一种天然化合物，参与神经元保护。研究表明，ALC可能是有效的预防和治疗CIPN.Patients和MethodsA 24周的随机双盲试验比较ALC（3,000毫克，每天）与安慰剂在接受辅助紫杉烷为基础的化疗的妇女进行。主要目的是确定ALC是否预防CIPN，如通过癌症治疗功能评估（FACT）-紫杉烷量表的11项神经毒性（NTX）组分在12周时所测量的。次要目标包括24周终点的变化，功能状态（FACT-试验结果指数[TOI]），疲劳（慢性疾病治疗[FACIT]-疲劳功能评估），和NTX grade.ResultsA共409例患者可评价（208接受ALC; 201，安慰剂）。在多变量线性回归中，ALC组第12周评分比安慰剂组低0.9分（CIPN更多）（95% CI，-2.2至0.4; P= 0.17），而ALC组第24周评分低1.8分（95% CI，-3.2至0.4; P= 0.01）。接受ALC治疗的患者更有可能出现FACT-NTX评分下降> 5分（38% vs 28%; P= 0.05），而接受ALC治疗的患者FACT-TOI评分降低3.5分（P= 0.03）。ALC组中3至4级神经毒性更常见（8对1）。在FACIT-疲乏或其他毒性方面未观察到组间差异。血清肉毒碱水平增加ALC，但保持稳定与placebo.ConclusionThere没有证据表明，ALC影响CIPN在12周，但是，ALC显着增加CIPN 24周。据我们所知，这是第一项表明营养补充剂增加CIPN的研究。不应鼓励患者使用未经证实有效的补充剂。(C)2013年美国临床肿瘤学会
PurposeChemotherapy-induced peripheral neuropathy (CIPN) is common and leads to suboptimal treatment. Acetyl-L-carnitine (ALC) is a natural compound involved in neuronal protection. Studies have suggested ALC may be effective for the prevention and treatment of CIPN.Patients and MethodsA 24-week randomized double-blind trial comparing ALC (3,000 mg per day) with placebo in women undergoing adjuvant taxane-based chemotherapy was conducted. The primary objective was to determine if ALC prevents CIPN as measured by the 11-item neurotoxicity (NTX) component of the Functional Assessment of Cancer Therapy (FACT) -Taxane scale at 12 weeks. Secondary objectives included changes in 24-week end points, functional status (FACT-Trial Outcome Index [TOI]), fatigue (Functional Assessment of Chronic Illness Therapy [FACIT]-Fatigue), and NTX grade.ResultsA total of 409 patients were evaluable (208 received ALC; 201, placebo). In a multivariate linear regression, week-12 scores were 0.9 points lower (more CIPN) with ALC than placebo (95% CI, -2.2 to 0.4; P=.17), whereas week-24 scores were 1.8 points lower with ALC (95% CI, -3.2 to -0.4; P=.01). Patients receiving ALC were more likely to have a > 5-point decrease in FACT-NTX scores (38% v 28%; P=.05), and FACT-TOI scores were 3.5 points lower with ALC (P=.03). Grade 3 to 4 neurotoxicity was more frequent in the ALC arm (eight v one). No differences between arms were observed for FACIT-Fatigue or other toxicities. Serum carnitine level increased with ALC but remained stable with placebo.ConclusionThere was no evidence that ALC affected CIPN at 12 weeks; however, ALC significantly increased CIPN by 24 weeks. This is the first study to our knowledge showing that a nutritional supplement increased CIPN. Patients should be discouraged from using supplements without proven efficacy. (C) 2013 by American Society of Clinical Oncology