De Nys Len, Barzegar-Fallah Anita, Lanckmans Katrien, Steurbaut Stephane, Beckwée David, de Haar-Holleman Amy, Provyn Steven, Gasthuys Elke, Vande Casteele Sofie, De Sutter Pieter-Jan, Vermeulen An, Van Bocxlaer Jan, Wuyts Stephanie C M, Adriaenssens Nele
Rehabilitation Research, Vrije Universiteit Brussel (VUB), Laarbeeklaan 121, 1090 Jette, Belgium.
Medical Oncology Department, Universitair Ziekenhuis Brussel (UZ Brussel), 1090 Jette, Belgium.
Cancers (Basel). 2024 Dec 27;17(1):50. doi: 10.3390/cancers17010050.
: Paclitaxel (PTX), a commonly used chemotherapy for breast cancer (BC), is associated with dose-limiting toxicities (DLTs) such as peripheral neuropathy and neutropenia. These toxicities frequently lead to dose reductions, treatment delays, or therapy discontinuation, negatively affecting patients' quality of life and clinical outcomes. Current dosing strategies based on body surface area (BSA) fail to account for individual variations in body composition (skeletal muscle mass (SMM) and adipose tissue (AT) mass) and physical activity (PA), which can influence drug metabolism and toxicity. This study aims to explore the relationships between PTX pharmacokinetics, body composition, and PA to predict DLTs. : This single-group observational cohort study will recruit 40 female BC patients undergoing PTX treatment. Data collection will include plasma PTX concentrations, body composition assessments (using dual X-ray absorptiometry and bioelectrical impedance analysis), PA measurements (via accelerometers), and questionnaires to assess BC-related health-related quality of life, chemotherapy-induced peripheral neuropathy, and neutropenia during the PTX schedule using validated questionnaires. Dose-limiting toxicities will be graded according to the Common Terminology Criteria for Adverse Events v5.0 (grade 3 or higher). This protocol is designed to develop a population-based PK-PD model that predicts the occurrence of chemotherapy-induced peripheral neuropathy and neutropenia in women with stage II or III BC undergoing PTX therapy, focusing on explanatory outcomes related to SMM, AT mass, and PA.
紫杉醇（PTX）是一种常用于治疗乳腺癌（BC）的化疗药物，会引发如周围神经病变和中性粒细胞减少等剂量限制性毒性（DLT）。这些毒性常常导致剂量减少、治疗延迟或治疗中断，对患者的生活质量和临床结局产生负面影响。当前基于体表面积（BSA）的给药策略未能考虑到身体组成（骨骼肌质量（SMM）和脂肪组织（AT）质量）以及身体活动（PA）的个体差异，而这些差异会影响药物代谢和毒性。本研究旨在探索PTX药代动力学、身体组成和PA之间的关系，以预测DLT。 ：这项单组观察性队列研究将招募40名接受PTX治疗的女性BC患者。数据收集将包括血浆PTX浓度、身体组成评估（使用双能X线吸收法和生物电阻抗分析）、PA测量（通过加速度计），以及使用经过验证的问卷来评估在PTX治疗期间与BC相关的健康相关生活质量、化疗引起的周围神经病变和中性粒细胞减少。剂量限制性毒性将根据《不良事件通用术语标准》第5.0版进行分级（3级或更高）。本方案旨在建立一个基于人群的PK-PD模型，以预测接受PTX治疗的II期或III期BC女性患者化疗引起的周围神经病变和中性粒细胞减少的发生情况，重点关注与SMM、AT质量和PA相关的解释性结果。
