Neurophysiological study of peripheral neuropathy after high-dose paclitaxel: Lack of neuroprotective effect of amifostine
Neurophysiological study of peripheral neuropathy after high-dose paclitaxel: Lack of neuroprotective effect of amifostine
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DOI：
10.1158/1078-0432.ccr-0772-03
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发表时间：
2004-01-15
影响因子：
11.5
通讯作者：
Somlo, G
中科院分区：
文献类型：
--
作者：
Openshaw, H;Beamon, K;Somlo, G
目的：探讨阿米福汀在预防或减轻大剂量紫杉醇所致神经病变中的作用。方法：乳腺癌患者接受大剂量紫杉醇(725 mg/m(2)/24 h)联合阿霉素(165 mg/m(2)/96 h)和环磷酰胺(100 mg/kg/2 h；ACT)两种自体外周血干细胞移植方案的研究，其中一种方案在开始应用紫杉醇前10分钟以上，另一种方案不加氨磷汀(740 mg/m(2))。治疗前及治疗后20~40天分别进行神经学检查、周围神经病变综合评分、腓、腓肠神经传导检查及定量感觉测试。结果：两组紫杉醇最大血药浓度、全身清除率及曲线下面积均无显著差异。在使用或不使用氨磷汀的受试者中，麻醉药物的需求和造血细胞计数的恢复也是相似的。经ACT治疗后，腓神经复合肌肉动作电位波幅和腓肠神经感觉动作电位波幅降低，振动和冷检测阈值升高。阿米福汀治疗后和治疗前的临床综合周围神经病变评分相似，治疗后和治疗前与治疗前比的对数显示阿米福汀对腓神经复合肌肉动作电位、腓肠神经感觉动作电位、振动检测阈值和冷检测阈值无显著影响。所有受试者在应用ACT后均有肢端感觉障碍和踝深肌腱反射消失。结论：单用大剂量紫杉醇可引起可预见的临床和神经生理学改变，因此接受大剂量紫杉醇治疗的患者是检验神经保护剂有效性的理想对象。氨磷汀不能预防或减轻大剂量紫杉醇的神经毒性。
Purpose: To determine if there is a beneficial effect of amifostine in preventing or reducing the neuropathy induced by high-dose paclitaxel.Methods: Breast cancer patients receiving high-dose infusional paclitaxel (725 mg/m(2)/24 h) in combination with doxorubicin (165 mg/m(2)/96 h) and cyclophosphamide (100 mg/kg/2 h; ACT) were studied on two autologous peripheral blood stem cell transplant protocols, one with and one without amifostine (740 mg/m(2) administered over 10 min before and 12 h after initiation of the paclitaxel infusion). Patients were evaluated before ACT and 20-40 days later with neurological examination, a composite peripheral neuropathy score, peroneal and sural nerve conduction studies, and quantitative sensory testing.Results: There was no significant difference in paclitaxel maximum concentration, systemic clearance, or area under the curve determinations. Narcotic requirement as well as recovery of hematopoietic counts were also similar in subjects with or without amifostine. After ACT was administered, there was a decrease in peroneal nerve compound muscle action potential amplitude and sural nerve sensory action potential amplitude, as well as an increase in vibratory and cold detection thresholds. Clinical composite peripheral neuropathy scores were similar despite amifostine treatment; and logarithm to the base 2 ratios post/pre ACT showed no significant effect of amifostine on peroneal nerve compound muscle action potential, sural nerve sensory action potential, vibratory detection thresholds, or cold detec-tion thresholds. All subjects had acroparesthesias and lost their ankle deep-tendon reflexes after administration of ACT.Conclusions: Single high-dose paclitaxel produces predictable clinical and neurophysiological changes so that patients receiving high-dose therapy are ideal subjects to test the effectiveness of neuroprotective agents. Amifostine was ineffective in preventing or reducing the neurotoxicity of high-dose paclitaxel.