Department of Pharmacy, Radboud University Medical Center, Radboud Institute for Health Sciences, Nijmegen, The Netherlands.
Department of Urology, Radboud University Medical Center, Nijmegen, The Netherlands.
Cancer Chemother Pharmacol. 2020 Apr;85(4):753-760. doi: 10.1007/s00280-020-04039-7. Epub 2020 Feb 19.
The aim of the study is to investigate the influence of patient characteristics, age and body mass index (BMI), on pharmacokinetics of enzalutamide, and to study the relationships between drug exposure and enzalutamide efficacy and toxicity, in mCRPC patients.
Data were collected in a longitudinal cohort study (ANDROPS) and a prospective observational study (ILUMINATE), both in mCRPC patients treated with enzalutamide. To investigate the influence of age and BMI on exposure, enzalutamide and N-desmethylenzalutamide levels were compared by ANOVA. To investigate the relation of exposure versus time to progression (TTP), the sum plasma levels were divided into quartiles and compared by Kaplan-Meier analysis. To assess the relation of exposure with fatigue, plasma levels in patients experiencing fatigue vs. no fatigue were compared by and independent t test.
Data of 68 mCRPC patients were included for analysis. Plasma levels were not different for age or BMI. No difference in TTP between both studies was observed (383 days (95% CI 287-859), and 567 days (95% CI 351-NR), p = 0.36). Kaplan-Meier analysis of quartiles of sum levels showed no difference for TTP. Fatigue was reported by 22 patients, no difference in sum plasma levels was observed between patients with and without fatigue.
We observed that age and BMI did not influence systemic exposure in patients treated with enzalutamide. No relation of exposure with efficacy or fatigue was observed. Further research using enzalutamide at a lower dose is needed to understand the relation of enzalutamide exposure and fatigue.
本研究旨在探讨患者特征、年龄和体重指数（BMI）对恩扎卢胺药代动力学的影响，并研究药物暴露与恩扎卢胺疗效和毒性之间的关系，以评估转移性去势抵抗性前列腺癌（mCRPC）患者。
数据来自一项纵向队列研究（ANDROPS）和一项前瞻性观察性研究（ILUMINATE），均纳入接受恩扎卢胺治疗的 mCRPC 患者。为了研究年龄和 BMI 对暴露的影响，采用方差分析比较恩扎卢胺和 N-去甲基恩扎卢胺的水平。为了研究暴露与无进展生存期（TTP）的关系，将总和血浆水平分为四分位数，并通过 Kaplan-Meier 分析进行比较。为了评估暴露与疲劳的关系，通过独立 t 检验比较出现疲劳和无疲劳的患者的血浆水平。
纳入 68 例 mCRPC 患者进行分析。年龄或 BMI 对血浆水平没有影响。两项研究之间的 TTP 无差异（383 天（95%CI 287-859）和 567 天（95%CI 351-NR），p=0.36）。总和水平四分位数的 Kaplan-Meier 分析显示 TTP 无差异。22 例患者报告出现疲劳，有疲劳和无疲劳患者的总和血浆水平无差异。
我们观察到，年龄和 BMI 对接受恩扎卢胺治疗的患者的系统暴露没有影响。未观察到暴露与疗效或疲劳之间存在关系。需要进一步研究恩扎卢胺的低剂量，以了解恩扎卢胺暴露与疲劳之间的关系。
