Argyriou A A, Zolota V, Kyriakopoulou O, Kalofonos H P
Department of Neurology, Saint Andrew's General Hospital of Patras, and Department of Pathology, University of Patras Medical School, Rion-Patras, Greece.
J BUON. 2010 Jul-Sep;15(3):435-46.
Peripheral neuropathy ranks among the most common non-haematological adverse effects of a number of effective chemotherapeutic agents, including platinum compounds, taxanes and vinca alkaloids. Newer agents, such as bortezomib, thalidomide and lenalidomide, frequently exert similar neurotoxic effects on peripheral nerves. Chemotherapy-induced peripheral neuropathy (CIPN) may result from a variety of mechanisms and may be related to causal factors, such as single dose per course, cumulative dose and risk factors including treatment schedule, prior or concomitant administration of other neurotoxic agents, age and pre-existing peripheral neuropathy of other causes. The symptoms usually begin during chemotherapy and they may even worsen after cessation of treatment. In most of the cases, patients experience positive (pain, paresthesias) or negative (numbness) sensory symptoms in distal extremities in a stocking-and-glove distribution with less prominent motor and autonomic involvement. To date, several neuroprotective agents including thiols, neurotrophic factors, anticonvulsants and antioxidants have been tested in preclinical models and clinical open label or randomized controlled trials for their ability to prevent or treat symptoms of CIPN. Although several of these agents hold promise as possible neuroprotective factors, clinical data are still controversial and none have as yet robustly been proven effective against CIPN. This review critically looks at the pathogenesis, incidence, risk factors, diagnosis, characteristics and management of peripheral neuropathy associated with commonly used chemotherapeutic agents. We also highlight areas of future research to pursue.
周围神经病变是多种有效化疗药物最常见的非血液学不良反应之一,这些药物包括铂类化合物、紫杉烷类和长春花生物碱。新型药物,如硼替佐米、沙利度胺和来那度胺,也常常对周围神经产生类似的神经毒性作用。化疗引起的周围神经病变(CIPN)可能由多种机制导致,并且可能与一些致病因素有关,如每疗程的单次剂量、累积剂量以及包括治疗方案、先前或同时使用其他神经毒性药物、年龄和其他原因引起的既往周围神经病变等风险因素。症状通常在化疗期间开始,甚至在治疗停止后可能会加重。在大多数情况下,患者在四肢远端出现呈袜套样和手套样分布的阳性(疼痛、感觉异常)或阴性(麻木)感觉症状,运动和自主神经受累相对较轻。迄今为止,包括硫醇、神经营养因子、抗惊厥药和抗氧化剂在内的几种神经保护剂已在临床前模型以及临床开放标签或随机对照试验中进行了测试,以评估它们预防或治疗CIPN症状的能力。尽管其中一些药物有望成为可能的神经保护因子,但临床数据仍存在争议,且尚无一种药物被确凿证明对CIPN有效。本综述批判性地探讨了与常用化疗药物相关的周围神经病变的发病机制、发病率、风险因素、诊断、特征和管理。我们还强调了未来需要开展研究的领域。
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