Matsuo Mitsuhiro, Ito Hisakatsu, Takemura Yoshinori, Hattori Mizuki, Kawakami Masaaki, Takahashi Norimasa, Yamazaki Mitsuaki
Department of Anesthesiology, Faculty of Medicine, University of Toyama, 2630 Sugitani, Toyama, 930-0194, Japan.
Department of Hospital Pharmacy, University of Toyama, Toyama, Japan.
J Anesth. 2017 Aug;31(4):631-635. doi: 10.1007/s00540-017-2362-y. Epub 2017 Apr 27.
Paclitaxel-induced peripheral neuropathy (PIPN) is one of the serious adverse events associated with paclitaxel-based cancer treatments. A recent case study showed that the antiplatelet agent clopidogrel inhibits paclitaxel metabolism via cytochrome P450 (CYP) 2C8, resulting in severe PIPN. The aim of this study was to determine the impact of clopidogrel as a risk factor for the development of PIPN, using a retrospective cohort study. Data from paclitaxel-treated patients with or without clopidogrel and low-dose aspirin treatment were retrieved from medical charts. A total of 161 adult patients were included in this study: 135 were controls, 9 were clopidogrel-treated and 17 were aspirin-treated. The clopidogrel group had a greater proportion of males and a higher rate of comorbidities, such as diabetes mellitus and dyslipidemia, than the control group. However, patient characteristics were similar between the clopidogrel and aspirin groups. Severe PIPN was diagnosed in 3 (2.2%) and 2 (22.2%) patients in the control and clopidogrel groups, respectively (odds ratio: 12.0; p = 0.031). No patients in the aspirin group presented with severe neuropathy. These pilot data suggest that concomitant treatment with clopidogrel leads to a greater risk of PIPN. The avoidance of concomitant clopidogrel use may be effective in reducing clopidogrel-associated PIPN.
紫杉醇引起的周围神经病变（PIPN）是基于紫杉醇的癌症治疗相关的严重不良事件之一。最近的一项病例研究表明，抗血小板药物氯吡格雷通过细胞色素P450（CYP）2C8抑制紫杉醇代谢，导致严重的PIPN。本研究的目的是通过一项回顾性队列研究确定氯吡格雷作为PIPN发生风险因素的影响。从病历中检索接受紫杉醇治疗且使用或未使用氯吡格雷及低剂量阿司匹林治疗的患者数据。本研究共纳入161例成年患者：135例为对照组，9例接受氯吡格雷治疗，17例接受阿司匹林治疗。氯吡格雷组男性比例更高，合并症（如糖尿病和血脂异常）发生率高于对照组。然而，氯吡格雷组和阿司匹林组的患者特征相似。对照组和氯吡格雷组分别有3例（2.2%）和2例（22.2%）患者被诊断为严重PIPN（比值比：12.0；p = 0.031）。阿司匹林组无患者出现严重神经病变。这些初步数据表明，氯吡格雷联合治疗会导致发生PIPN的风险更高。避免联合使用氯吡格雷可能有效降低与氯吡格雷相关的PIPN。
