Adriaenssens Nele, Wuyts Stephanie C M, Steurbaut Stephane, De Sutter Pieter-Jan, Vermeulen An, de Haar-Holleman Amy, Beckwée David, Provyn Steven, Vande Casteele Sofie, Zhou Jinyu, Lanckmans Katrien, Van Bocxlaer Jan, De Nys Len
Rehabilitation Research, Vrije Universiteit Brussel (VUB), Laarbeeklaan 121, 1090 Brussels, Belgium.
Medical Oncology Department, Universitair Ziekenhuis Brussel (UZ Brussel), Laarbeeklaan 101, 1090 Brussels, Belgium.
Cancers (Basel). 2025 Apr 9;17(8):1271. doi: 10.3390/cancers17081271.
BACKGROUND/OBJECTIVES: Paclitaxel is a type of small molecule chemotherapy widely used for breast cancer, but its clinical efficacy is often hindered by dose-limiting toxicities such as chemotherapy-induced peripheral neuropathy and neutropenia. Traditional dosing based on body surface area does not account for variations in body composition, which may influence paclitaxel metabolism, toxicity, and treatment outcomes. This review explores the interplay between body composition, physical activity, and paclitaxel pharmacokinetics, emphasizing the potential for personalized dosing strategies.
A comprehensive narrative review was conducted by analyzing the literature on body composition, small molecule chemotherapy-related toxicities, pharmacokinetics, and exercise oncology. Studies examining the role of skeletal muscle mass, adipose tissue, and physical activity in modulating paclitaxel metabolism and side effects were included.
Evidence suggests that patients with low skeletal muscle mass are at a higher risk of paclitaxel-induced toxicities due to altered drug distribution and clearance. Sarcopenic obesity, characterized by low muscle and high-fat levels, further exacerbates these risks. Exercise, particularly resistance and aerobic training, has been shown to improve muscle mass, mitigate toxicities, and enhance chemotherapy tolerance. However, the precise mechanisms by which exercise influences paclitaxel pharmacokinetics remain underexplored.
Personalized chemotherapy dosing, considering body composition and physical activity, may optimize paclitaxel treatment outcomes. Future research should focus on integrating exercise interventions into oncology care and refining dosing models that account for interindividual differences in drug metabolism. These advancements could improve treatment efficacy while minimizing toxicities in breast cancer patients.
背景/目的：紫杉醇是一种广泛用于治疗乳腺癌的小分子化疗药物，但其临床疗效常受到化疗诱导的周围神经病变和中性粒细胞减少等剂量限制性毒性的阻碍。基于体表面积的传统给药方式未考虑身体成分的差异，而这种差异可能会影响紫杉醇的代谢、毒性和治疗效果。本综述探讨了身体成分、体力活动与紫杉醇药代动力学之间的相互作用，强调了个性化给药策略的潜力。
通过分析有关身体成分、小分子化疗相关毒性、药代动力学和运动肿瘤学的文献，进行了一项全面的叙述性综述。纳入了研究骨骼肌质量、脂肪组织和体力活动在调节紫杉醇代谢和副作用中作用的研究。
有证据表明，骨骼肌质量低的患者因药物分布和清除改变，发生紫杉醇诱导毒性的风险更高。以低肌肉量和高脂肪水平为特征的肌少症肥胖会进一步加剧这些风险。运动，尤其是抗阻训练和有氧运动，已被证明可以增加肌肉量、减轻毒性并提高化疗耐受性。然而，运动影响紫杉醇药代动力学的具体机制仍有待深入研究。
考虑身体成分和体力活动的个性化化疗给药可能会优化紫杉醇的治疗效果。未来的研究应侧重于将运动干预纳入肿瘤护理，并完善考虑个体药物代谢差异的给药模型。这些进展可以提高治疗效果，同时将乳腺癌患者的毒性降至最低。
