相关实验视频

Updated: May 13, 2025

Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts

Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts

Published on: July 25, 2020

在真实世界癌症患者中,以模型为基础优化帕佐帕尼布的剂量

Zhiyuan Tan^1,2, Swantje Völler¹, Anyue Yin²

¹Division of Systems Pharmacology and Pharmacy, Leiden Academic Center for Drug Research, Leiden University, Leiden, The Netherlands.

Clinical pharmacokinetics

|April 22, 2025

概括

将巴佐帕尼布初始剂量降至每天600毫克,可能显著降低转移性细胞癌 (mRCC) 和软组织肉瘤 (STS) 患者的肝毒性风险. 这种剂量调整,结合精确剂量,旨在改善pazopanib疗效与安全之间的平衡.

科学领域:

药理动力学和药理动力学
在瘤学瘤学.
药品安全药品安全

背景情况:

帕佐帕尼布已被批准用于转移性细胞癌 (mRCC) 和软组织肉瘤 (STS) 在禁食条件下每天服用800毫克 (QD).
由于毒性导致的剂量减少发生在~60%的患者中,严重的肝毒性发生在>10%的患者中,需要暂停治疗.
对于mRCC的确定的疗效目标是最低度 (Cmin,ss) ≥20.5 mg/L,但肝毒性没有特定的值.

研究的目的:

开发人群药理动力学 (POPPK) 和暴露-反应模型,用于pazopanib.
建立暴露肝脏毒性值以优化剂量.
为现实患者优化巴佐帕尼布的初始剂量,以平衡疗效和毒性.

主要方法:

开发了一个POPPK模型,使用460个度测量来自135名用帕佐帕尼布治疗的患者 (中位初始剂量为800毫克QD).
使用时间到事件建模评估了暴露肝脏毒性.
使用瘤生长建模评估了暴露-瘤大小动态.

主要成果:

超过34mg/L的Cmin,ss值与3.35倍的2级或以上肝毒性风险增加有关 (P<0.01).
模拟表明,初始剂量为600mgQD显著降低了肝毒性风险 (P < 0.001),同时在76%的患者中保持Cmin,ss ≥20.5 mg/L.
瘤生长和衰变率在mRCC和STS之间有所不同,但不依赖于帕佐帕尼布暴露,这表明目前水平的最大瘤抑制.

结论:

禁食时600毫克的帕佐帕尼布初始剂量可以改善疗效-毒性平衡.
基于模型的精确剂量,以保持Cmin,ss在20至34毫克/升之间,可以减轻治疗中断.
优化pazopanib剂量可能会改善mRCC和STS患者的治疗结果.

更多相关视频

Profiling Sensitivity to Targeted Therapies in EGFR-Mutant NSCLC Patient-Derived Organoids

Profiling Sensitivity to Targeted Therapies in EGFR-Mutant NSCLC Patient-Derived Organoids

Published on: November 22, 2021

Establishment of Zebrafish Patient-Derived Xenografts from Pancreatic Cancer for Chemosensitivity Testing

Establishment of Zebrafish Patient-Derived Xenografts from Pancreatic Cancer for Chemosensitivity Testing

Published on: May 12, 2023

相关概念视频

Combination Therapies and Personalized Medicine

Combination Therapies and Personalized Medicine

Combining two or more treatment methods increases the life span of cancer patients while reducing damage to vital organs or tissue from the overuse of a single treatment. Combination therapy also targets different cancer-inducing pathways, thus reducing the chances of developing resistance to treatment.
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...

Analysis of Population Pharmacokinetic Data

Analysis of Population Pharmacokinetic Data

Analysis of population pharmacokinetic data involves studying the behavior of drugs within diverse populations to understand their pharmacokinetic parameters. Traditional pharmacokinetic methods typically involve collecting samples from a few individuals and estimating these parameters. While these methods are commonly used, they have limitations in capturing the variability in drug response among individuals or heterogeneous populations. Population pharmacokinetics is employed to address these...

Model Approaches for Pharmacokinetic Data: Distributed Parameter Models

Model Approaches for Pharmacokinetic Data: Distributed Parameter Models

Pharmacokinetic models are mathematical constructs that represent and predict the time course of drug concentrations in the body, providing meaningful pharmacokinetic parameters. These models are categorized into compartment, physiological, and distributed parameter models.
The distributed parameter models are specifically designed to account for variations and differences in some drug classes. This model is particularly useful for assessing regional concentrations of anticancer or...