Department of Clinical Pharmacy, University of Michigan College of Pharmacy, 428 Church St., Room 3054, Ann Arbor, MI, 48109-1065, USA.
University of Alabama at Birmingham School of Nursing, Birmingham, AL, USA.
Breast Cancer Res Treat. 2022 Aug;194(3):551-560. doi: 10.1007/s10549-022-06652-x. Epub 2022 Jun 28.
Chemotherapy-induced peripheral neuropathy (CIPN) is the major treatment-limiting toxicity of paclitaxel, which predominantly presents as sensory symptoms, with motor symptoms in some patients. Differentiating CIPN into subtypes has been recommended to direct CIPN research. The objective of this study was to investigate whether sensory and motor CIPN are distinct subtypes with different predictive biomarkers in patients with breast cancer receiving paclitaxel.
Data were from a prospective cohort of 60 patients with breast cancer receiving up to 12 weekly infusions of 80 mg/m paclitaxel (NCT02338115). European Organisation for Research and Treatment of Cancer Quality of Life questionnaire CIPN20 was used to evaluate CIPN. Clusters of the time course of sensory (CIPN), motor (CIPN), and the difference between sensory and motor (CIPN-CIPN) were identified using k-means clustering on principal component scores. Predictive metabolomic biomarkers of maximum CIPN and CIPN were investigated using linear regressions adjusted for baseline CIPN, paclitaxel pharmacokinetics, and body mass index.
More sensory than motor CIPN was found (CIPN change: mean = 10.8, ranged [-3.3, 52.1]; CIPN change: mean = 3.5, range: [-7.5, 35.0]). Three groups were identified with No CIPN, Mixed CIPN, and Sensory-dominant CIPN (maximum CIPN: mean = 12.7 vs. 40.9 vs. 74.3, p < 0.001; maximum CIPN: mean = 5.4 vs. 25.5 vs. 36.1, p < 0.001; average CIPN-CIPN: mean = 2.8 vs. 5.8 vs. 24.9, p < 0.001). Biomarkers of motor CIPN were similar to previously identified biomarkers of sensory CIPN, including lower serum histidine (p = 0.029).
Our findings suggest that sensory and motor CIPN co-occur and may not have differentiating metabolic biomarkers. These findings need to be validated in larger cohorts of patients treated with paclitaxel and other neurotoxic agents to determine the optimal approach to predict, prevent, and treat CIPN and improve patients' outcomes.
化疗引起的周围神经病（CIPN）是紫杉醇的主要治疗限制毒性，主要表现为感觉症状，部分患者出现运动症状。将 CIPN 分为亚型已被推荐用于指导 CIPN 研究。本研究的目的是探讨接受紫杉醇治疗的乳腺癌患者的 CIPN 是否存在感觉和运动亚型，这些亚型具有不同的预测生物标志物。
数据来自前瞻性队列 60 例接受多达 12 周每周 80mg/m 紫杉醇（NCT02338115）的乳腺癌患者。欧洲癌症研究与治疗组织生活质量问卷 CIPN20 用于评估 CIPN。使用主成分得分的 k-均值聚类来识别感觉（CIPN）、运动（CIPN）和感觉与运动之间差异（CIPN-CIPN）的时间过程聚类。使用线性回归分析调整基线 CIPN、紫杉醇药代动力学和体重指数后，研究最大 CIPN 和 CIPN 的预测代谢组学生物标志物。
发现感觉 CIPN 多于运动 CIPN（CIPN 变化：均值=10.8，范围[-3.3，52.1]；CIPN 变化：均值=3.5，范围：[-7.5，35.0]）。确定了三组无 CIPN、混合 CIPN 和感觉优势 CIPN（最大 CIPN：均值=12.7 vs. 40.9 vs. 74.3，p<0.001；最大 CIPN：均值=5.4 vs. 25.5 vs. 36.1，p<0.001；平均 CIPN-CIPN：均值=2.8 vs. 5.8 vs. 24.9，p<0.001）。运动 CIPN 的生物标志物与先前鉴定的感觉 CIPN 生物标志物相似，包括血清组氨酸水平降低（p=0.029）。
我们的研究结果表明，感觉和运动 CIPN 同时发生，可能没有区别代谢生物标志物。这些发现需要在接受紫杉醇和其他神经毒性药物治疗的更大患者队列中进行验证，以确定预测、预防和治疗 CIPN 以及改善患者结局的最佳方法。
