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成人化疗引起的周围神经病变:文献综述

Chemotherapy-induced peripheral neuropathy in adults: a comprehensive update of the literature.

作者信息

Argyriou Andreas A, Kyritsis Athanasios P, Makatsoris Thomas, Kalofonos Haralabos P

机构信息

Department of Neurology, "Saint Andrew's" General Hospital of Patras, Greece ; Department of Medicine-Division of Oncology, University of Patras Medical School, Rion-Patras, Greece.

Department of Neurology, University Hospital of Ioannina, Greece.

出版信息

Cancer Manag Res. 2014 Mar 19;6:135-47. doi: 10.2147/CMAR.S44261. eCollection 2014.

Abstract

Commonly used chemotherapeutic agents in oncology/hematology practice, causing toxic peripheral neuropathy, include taxanes, platinum compounds, vinca alkaloids, proteasome inhibitors, and antiangiogenic/immunomodulatory agents. This review paper intends to put together and discuss the spectrum of chemotherapy-induced peripheral neuropathy (CIPN) characteristics so as to highlight areas of future research to pursue on the topic. Current knowledge shows that the pathogenesis of CIPN still remains elusive, mostly because there are several sites of involvement in the peripheral nervous system. In any case, it is acknowledged that the dorsal root ganglia of the primary sensory neurons are the most common neural targets of CIPN. Both the incidence and severity of CIPN are clinically under- and misreported, and it has been demonstrated that scoring CIPN with common toxicity scales is associated with significant inter-observer variability. Only a proportion of chemotherapy-treated patients develop treatment-emergent and persistent CIPN, and to date it has been impossible to predict high-and low-risk subjects even within groups who receive the same drug regimen. This issue has recently been investigated in the context of pharmacogenetic analyses, but these studies have not implemented a proper methodological approach and their results are inconsistent and not really clinically relevant. As such, a stringent approach has to be implemented to validate that information. Another open issue is that, at present, there is insufficient evidence to support the use of any of the already tested chemoprotective agents to prevent or limit CIPN. The results of comprehensive interventions, including clinical, neurophysiological, and pharmacogenetic approaches, are expected to produce a consistent advantage for both doctors and patients and thus allow the registration and analysis of reliable data on the true characteristics of CIPN, eventually leading to potential preventive and therapeutic interventions.

摘要

肿瘤学/血液学实践中常用的可导致毒性周围神经病变的化疗药物包括紫杉烷类、铂类化合物、长春花生物碱、蛋白酶体抑制剂以及抗血管生成/免疫调节药物。本综述旨在汇总并讨论化疗诱导的周围神经病变(CIPN)的特征范围,以突出该主题未来的研究方向。目前的知识表明,CIPN的发病机制仍然难以捉摸,主要是因为周围神经系统有多个受累部位。无论如何,公认的是,初级感觉神经元的背根神经节是CIPN最常见的神经靶点。CIPN的发病率和严重程度在临床上报导不足且存在错误报告,并且已经证明,使用常见毒性量表对CIPN进行评分会存在显著的观察者间差异。只有一部分接受化疗的患者会出现治疗中出现的持续性CIPN,迄今为止,即使在接受相同药物方案的组内,也无法预测高风险和低风险受试者。最近在药物遗传学分析的背景下对这个问题进行了研究,但这些研究没有采用适当的方法,其结果不一致且与临床实际相关性不大。因此,必须采用严格的方法来验证这些信息。另一个未解决的问题是,目前没有足够的证据支持使用任何已测试的化学保护剂来预防或限制CIPN。包括临床、神经生理学和药物遗传学方法在内的综合干预结果,有望为医生和患者带来一致的益处,从而能够对CIPN的真实特征进行可靠数据的记录和分析,最终促成潜在的预防和治疗干预措施。

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