Verstappen Carla C P, Heimans Jan J, Hoekman Klaas, Postma Tjeerd J
Department of Neurology, VU University Medical Center, Amsterdam, The Netherlands.
Drugs. 2003;63(15):1549-63. doi: 10.2165/00003495-200363150-00003.
Neurotoxic side effects of chemotherapy occur frequently and are often a reason to limit the dose of chemotherapy. Since bone marrow toxicity, as the major limiting factor in most chemotherapeutic regimens, can be overcome with growth factors or bone marrow transplantation, the use of higher doses of chemotherapy is possible, which increases the risk of neurotoxicity. Chemotherapy may cause both peripheral neurotoxicity, consisting mainly of a peripheral neuropathy, and central neurotoxicity, ranging from minor cognitive deficits to encephalopathy with dementia or even coma. In this article we describe the neurological adverse effects of the most commonly used chemotherapeutic agents. The vinca-alkaloids, cisplatin and the taxanes are amongst the most important drugs inducing peripheral neurotoxicity. These drugs are widely used for various malignancies such as ovarian and breast cancer, and haematological cancers. Chemotherapy-induced neuropathy is clearly related to cumulative dose or dose-intensities. Patients who already have neuropathic symptoms due to diabetes mellitus, hereditary neuropathies or earlier treatment with neurotoxic chemotherapy are thought to be more vulnerable for the development of chemotherapy-induced peripheral neuropathy. Methotrexate, cytarabine (cytosine arabinoside) and ifosfamide are primarily known for their central neurotoxic side effects. Central neurotoxicity ranges from acute toxicity such as aseptic meningitis, to delayed toxicities comprising cognitive deficits, hemiparesis, aphasia and progressive dementia. Risk factors are high doses, frequent administration and radiotherapy preceding methotrexate chemotherapy, which appears to be more neurotoxic than methotrexate as single modality. Data on management and neuroprotective agents are discussed. Management mainly consists of cumulative dose-reduction or lower dose-intensities, especially in patients who are at higher risk to develop neurotoxic side effects. None of the neuroprotective agents described in this article can be recommended for standard use in daily practise at this moment, and further studies are needed to confirm some of the beneficial effects described.
化疗的神经毒性副作用经常发生，且常常是限制化疗剂量的一个原因。由于骨髓毒性作为大多数化疗方案中的主要限制因素，可通过生长因子或骨髓移植来克服，因此使用更高剂量的化疗成为可能，这增加了神经毒性的风险。化疗可导致外周神经毒性（主要表现为外周神经病变）和中枢神经毒性（范围从轻微的认知缺陷到伴有痴呆甚至昏迷的脑病）。在本文中，我们描述了最常用化疗药物的神经学不良反应。长春花生物碱、顺铂和紫杉烷是诱导外周神经毒性的最重要药物。这些药物广泛用于治疗各种恶性肿瘤，如卵巢癌、乳腺癌和血液系统癌症。化疗引起的神经病变显然与累积剂量或剂量强度有关。由于糖尿病、遗传性神经病变或先前接受过神经毒性化疗而已经出现神经病变症状的患者，被认为更容易发生化疗引起的外周神经病变。甲氨蝶呤、阿糖胞苷（胞嘧啶阿拉伯糖苷）和异环磷酰胺主要因其中枢神经毒性副作用而为人所知。中枢神经毒性范围从急性毒性如无菌性脑膜炎，到包括认知缺陷、偏瘫、失语和进行性痴呆在内的迟发性毒性。风险因素包括高剂量、频繁给药以及甲氨蝶呤化疗前的放疗，放疗作为单一治疗方式似乎比甲氨蝶呤更具神经毒性。本文还讨论了管理措施和神经保护剂。管理主要包括减少累积剂量或降低剂量强度，特别是对于发生神经毒性副作用风险较高的患者。目前本文中描述的神经保护剂均不推荐在日常实践中常规使用，需要进一步研究来证实所描述的一些有益效果。
