Unit of Neuro-Oncology, Hospital Universitari de Bellvitge-ICO Duran i Reynals, , Barcelona, Spain.
J Neurol Neurosurg Psychiatry. 2014 Apr;85(4):392-8. doi: 10.1136/jnnp-2013-305334. Epub 2013 Jun 29.
Peripheral neuropathy ranks among the most common dose-limiting and disabling side-effect of oxaliplatin (OXA)-based chemotherapy. The aim of this prospective, multicentre study was to define early clinical and neurophysiological markers that may help to identify patients at risk of developing severe, treatment emergent, cumulative OXA-induced peripheral neuropathy (OXAIPN).
200 colorectal cancer patients, scheduled to receive OXA-based chemotherapy, were prospectively followed. Detailed neurological assessment employing the clinical Total Neuropathy Score (TNSc), oncological rating scales (National Common Institute-Common Toxicity Criteria V.3) and nerve conduction studies (NCS) were performed at baseline, mid-treatment and at the end of chemotherapy. Symptoms of OXA-induced acute neurotoxicity were systematically recorded.
According to TNSc, 36 (18%) patients developed grade 3 OXAIPN. These patients were predominantly men (p=0.005), presented a significant decrease in all NCS (p<0.001), reported more acute neuropathic symptoms (p<0.001) and received higher OXA cumulative dose (p=0.003). Multivariate analysis showed that three variables obtained at intermediate follow-up, namely, the number of acute symptoms (OR 1.9; CI 95% 1.2 to 3.2; p=0.012) and the >30% decrease in sensory nerve action potential amplitude from the baseline value in radial (OR 41.4; CI 95% 4.98 to 343.1; p=0.001) and dorsal sural nerves (OR 24.96; CI 95% 2.6 to 239.4; p=0.005) were independently associated with the risk of developing severe OXAIPN.
High-grade OXA neurotoxicity can be predicted by clinical and neurophysiological information obtained at mid-treatment. Neurological assessment of acute neuropathy symptoms and radial and dorsal sural nerves NCS should be carefully monitored to predict and hopefully prevent the induction of severe OXAIPN.
周围神经病变是奥沙利铂（OXA）为基础的化疗中最常见的剂量限制和致残的副作用之一。本前瞻性多中心研究的目的是确定早期临床和神经生理学标志物，以帮助识别发生严重、治疗性、累积性奥沙利铂诱导的周围神经病（OXAIPN）风险的患者。
200 例计划接受 OXA 为基础化疗的结直肠癌患者前瞻性随访。在基线、治疗中期和化疗结束时进行详细的神经学评估，采用临床总神经病变评分（TNSc）、肿瘤学评分量表（国家癌症研究所-常见毒性标准 V.3）和神经传导研究（NCS）。系统记录奥沙利铂诱导的急性神经毒性的症状。
根据 TNSc，36 例（18%）患者发生 3 级 OXAIPN。这些患者主要为男性（p=0.005），所有 NCS 均显著下降（p<0.001），报告更多的急性神经病变症状（p<0.001），且接受的 OXA 累积剂量更高（p=0.003）。多变量分析显示，中期随访时获得的三个变量，即急性症状的数量（OR 1.9；95%CI 1.2 至 3.2；p=0.012）和桡神经（OR 41.4；95%CI 4.98 至 343.1；p=0.001）和腓肠神经（OR 24.96；95%CI 2.6 至 239.4；p=0.005）的感觉神经动作电位幅度从基线值下降>30%，与发生严重 OXAIPN 的风险独立相关。
可通过治疗中期获得的临床和神经生理学信息预测高等级 OXA 神经毒性。应仔细监测急性神经病变症状和桡神经和腓肠神经 NCS 的神经学评估，以预测并希望预防严重的 OXAIPN 的发生。
