目的:化疗诱导的周围神经病变(CIPN)是限制nab-紫杉醇(Nab-P)治疗胰腺癌患者的主要毒性。这项研究的目的是使用患者报告的结果测量和微创体积吸收微量采样(VAMS)技术来确定影响CIPN的因素。
方法:从44名胰腺癌参与者收集的81个VAMS样品中测量了紫杉醇的最大浓度(Cmax)。CIPN发展与人口统计之间的关联,临床和药代动力学因素使用单变量和多变量逻辑回归确定.使用Spearman等级相关性评估CIPN严重程度与因素之间的关联。使用多变量线性回归评估Cmax和治疗周期数对严重程度的影响。
结果:CIPN的发展与累积剂量显着相关(比值比1.005,95%置信区间[CI]1.003-1.007),治疗周期(3.47,2.25-5.85),碱性磷酸盐(0.992,0.985-0.998)和年龄(1.092,1.020-1.179),受试者工作特征曲线下面积为0.89(95%CI0.83-0.95)。CIPN的严重程度随着累积剂量的增加而显著恶化(系数0.58,95%CI0.44-0.69),治疗周期(0.57,0.44-0.68)和年龄(0.18,0.00-0.35)。CIPN的严重程度可从治疗周期(P=.0002)和Cmax(P=.01)预测。
结论:Nab-P的累积剂量越高,治疗周期和年龄,患者经历CIPN的频率和严重程度越高。在使用Cmax预测CIPN的严重程度时,微创VAMS是静脉采血的可行替代方法。
OBJECTIVE: Chemotherapy-induced peripheral neuropathy (CIPN) is a major toxicity limiting the use of nab-paclitaxel (Nab-P) in treating patients with pancreatic cancer. The aim of this study was to identify the factors affecting CIPN using patient-reported outcome measures and the minimally invasive volumetric absorptive microsampling (VAMS) technique.
METHODS: The maximum concentrations of paclitaxel (Cmax) were measured from 81 VAMS samples collected from 44 participants with pancreatic cancer. The association between CIPN development and demographic, clinical and pharmacokinetic factors was determined using univariable and multivariable logistic regression. The association between CIPN severity and the factors was evaluated using Spearman\'s rank correlation. The impact of Cmax and the number of treatment cycles on the severity was assessed using multivariable linear regression.
RESULTS: The development of CIPN was significantly associated with cumulative dose (odds ratio 1.005, 95% confidence interval [CI] 1.003-1.007), treatment cycles (3.47, 2.25-5.85), alkaline phosphate (0.992, 0.985-0.998) and age (1.092, 1.020-1.179), with an area under the receiver operating characteristic curve of 0.89 (95% CI 0.83-0.95). The severity of CIPN significantly worsened with increasing cumulative dose (coefficient 0.58, 95% CI 0.44-0.69), treatment cycles (0.57, 0.44-0.68) and age (0.18, 0.00-0.35). The severity of CIPN was predictable from treatment cycles (P = .0002) and Cmax (P = .01).
CONCLUSIONS: The higher the cumulative dose of Nab-P, treatment cycles and age, the more frequently and severely do the patients experience CIPN. In predicting the severity of CIPN using Cmax, minimally invasive VAMS is a feasible alternative to venous blood sampling.