Two-Year Trends of Taxane-Induced Neuropathy in Women Enrolled in a Randomized Trial of Acetyl-L-Carnitine (SWOG S0715)
Two-Year Trends of Taxane-Induced Neuropathy in Women Enrolled in a Randomized Trial of Acetyl-L-Carnitine (SWOG S0715)
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DOI：
10.1093/jnci/djx259
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发表时间：
2018-06-01
影响因子：
10.3
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.
背景：化疗引起的周围神经病变（CIPN）是紫杉烷类药物常见的致残性副作用。在一项随机试验中，乙酰- l- camitine （ALC）出乎意料地增加了CIPN。在这项试验中，我们调查了患者CIPN的长期模式。方法：S0715是一项随机、双盲、多中心试验，比较了接受紫杉烷辅助化疗的乳腺癌妇女的ALC （1000 mg，每天3次）和安慰剂，为期24周。在第12、24、36、52和104周，通过FACT-Taxane量表的11项神经毒性（NTX）成分来测量CIPN。我们使用纵向数据的线性混合模型检查了两年来的NTX分数。个别时间点采用线性回归进行检验。回归分析包括分层因素和基线评分作为协变量。所有统计检验均为双侧检验。结果：490名受试者符合评价条件。与安慰剂组相比，接受ALC治疗的患者NTX评分（CIPN较差）降低了-1.39分（95%可信区间[CI] = -2.48至-0.30），具有统计学意义（P = 0.01）。这些差异在第24周（-1.68,95% CI = -3.02至-0.33）、第36周（-1.37,95% CI = -2.69至-0.04）和第52周（-1.83,95% CI = -3.35至-0.32）时尤为明显。在104周时，ALC组的39.5%和安慰剂组的34.4%报告较基线下降了5个百分点（10%）。两组患者104周NTX评分与基线比较差异均有统计学意义（P < 0.001）。结论：两组患者的NTX评分均较基线有所降低，且持续保持较低水平。24周的ALC治疗导致两年内CIPN显著恶化。了解这种持续效应的机制可以为预防和治疗策略提供信息。在此之前，应该严格研究常用补充剂的潜在功效和危害。
Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a common and disabling side effect of taxanes. Acetyl-L-camitine (ALC) was unexpectedly found to increase CIPN in a randomized trial. We investigated the long-term patterns of CIPN among patients in this trial.Methods: S0715 was a randomized, double-blind, multicenter trial comparing ALC (1000 mg three times a day) with placebo for 24 weeks in women undergoing adjuvant taxane-based chemotherapy for breast cancer. CIPN was measured by the 11-item neurotoxicity (NTX) component of the FACT-Taxane scale at weeks 12, 24, 36, 52, and 104. We examined NTX scores over two years using linear mixed models for longitudinal data. Individual time points were examined using linear regression. Regression analyses included stratification factors and the baseline score as covariates. All statistical tests were two-sided.Results: Four-hundred nine subjects were eligible for evaluation. Patients receiving ALC had a statistically significantly (P = .01) greater reduction in NTX scores (worse CIPN) of -1.39 points (95% confidence interval [CI] = -2.48 to -0.30) than the placebo group. These differences were particularly evident at weeks 24 (-1.68, 95% CI = -3.02 to -0.33), 36 (-1.37, 95% CI = -2.69 to -0.04), and 52 (-1.83, 95% CI = -3.35 to -0.32). At 104 weeks, 39.5% on the ALC arm and 34.4% on the placebo arm reported a five-point (10%) decrease from baseline. For both treatment groups, 104-week NTX scores were statistically significantly different compared with baseline (P < .001).Conclusions: For both groups, NTX scores were reduced from baseline and remained persistently low. Twenty-four weeks of ALC therapy resulted in statistically significantly worse CIPN over two years. Understanding the mechanism of this persistent effect may inform prevention and treatment strategies. Until then, the potential efficacy and harms of commonly used supplements should be rigorously studied.