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[抗癌药物的药代动力学与治疗药物监测]

[Pharmacokinetics and therapeutic drug monitoring of anticancer agents].

作者信息

Marquet Pierre, Rousseau Annick

机构信息

Inserm U850, CHU Dupuytren, 2, avenue Martin-Luther-King, 87042 Limoges Cedex.

出版信息

Bull Cancer. 2008 Oct;95(10):903-9. doi: 10.1684/bdc.2008.0725.

Abstract

Treatment individualisation, an old concept renovated by the progress of analytical techniques and the advent of pharmacogenetics, aims at optimizing the usage of existing drugs by adjusting the nature and dose of anticancer agents to each patient, based on genetic, physiological and pathological criteria, on tumour nature, on associated drugs or previous treatment lines, on treatment efficacy and toxicity or on patient's exposure to the active drug form. This article exposes the pre-requisites and clinical trials necessary to demonstrate the usefulness of therapeutic drug monitoring (TDM) for drugs in general and anticancer agents in particular. It also presents the different TDM approaches used in oncology and reviews the current situation of anticancer drugs' TDM. When TDM cannot be expected to optimize efficacy, it may at least contribute to secure high dose regimens in intensification protocols. TDM in oncology is a discipline in progress. Proofs of efficacy are both scarce are difficult to obtain. However, taking this limitation into account and using the benefits of technical progress could lead to better cognitive research on the predictive response factors for a larger number of anticancer agents in the future. When the usefulness of TDM has been clinically demonstrated or strongly suggested, it is essential that as many patients as possible benefit from it. This "technological transfer" is a continuous process that requires periodical reviews of research results for TDM specialists and clinicians.

摘要

治疗个体化是一个因分析技术进步和药物遗传学出现而革新的古老概念,旨在根据遗传、生理和病理标准、肿瘤性质、联合用药或既往治疗方案、治疗疗效和毒性或患者对活性药物形式的暴露情况,为每位患者调整抗癌药物的种类和剂量,从而优化现有药物的使用。本文阐述了证明治疗药物监测(TDM)对一般药物尤其是抗癌药物有用性所需的先决条件和临床试验。它还介绍了肿瘤学中使用的不同TDM方法,并综述了抗癌药物TDM的现状。当无法期望TDM优化疗效时,它至少有助于在强化方案中确保高剂量治疗方案的安全性。肿瘤学中的TDM是一门不断发展的学科。疗效证据既稀缺又难以获得。然而,考虑到这一局限性并利用技术进步的优势,未来可能会对更多抗癌药物的预测反应因素进行更好的认知研究。当TDM的有用性在临床上得到证实或强烈提示时,至关重要的是让尽可能多的患者从中受益。这种“技术转移”是一个持续的过程,需要TDM专家和临床医生定期审查研究结果。

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