靶向抗癌蛋白激酶抑制剂在常规临床应用中的治疗药物监测：批判性评价。

Therapeutic Drug Monitoring of Targeted Anticancer Protein Kinase Inhibitors in Routine Clinical Use: A Critical Review.

机构信息

Service of Clinical Pharmacology, Lausanne University Hospital and University of Lausanne.

Institute of Pharmaceutical Sciences of Western, University of Geneva, Geneva, Switzerland.

出版信息

Ther Drug Monit. 2020 Feb;42(1):33-44. doi: 10.1097/FTD.0000000000000699.

DOI:10.1097/FTD.0000000000000699

PMID:31479043

Abstract

BACKGROUND

Therapeutic response to oral targeted anticancer protein kinase inhibitors (PKIs) varies widely between patients, with insufficient efficacy of some of them and unacceptable adverse reactions of others. There are several possible causes for this heterogeneity, such as pharmacokinetic (PK) variability affecting blood concentrations, fluctuating medication adherence, and constitutional or acquired drug resistance of cancer cells. The appropriate management of oncology patients with PKI treatments thus requires concerted efforts to optimize the utilization of these drug agents, which have probably not yet revealed their full potential.

METHODS

An extensive literature review was performed on MEDLINE on the PK, pharmacodynamics, and therapeutic drug monitoring (TDM) of PKIs (up to April 2019).

RESULTS

This review provides the criteria for determining PKIs suitable candidates for TDM (eg, availability of analytical methods, observational PK studies, PK-pharmacodynamics relationship analysis, and randomized controlled studies). It reviews the major characteristics and limitations of PKIs, the expected benefits of TDM for cancer patients receiving them, and the prerequisites for the appropriate utilization of TDM. Finally, it discusses various important practical aspects and pitfalls of TDM for supporting better implementation in the field of cancer treatment.

CONCLUSIONS

Adaptation of PKIs dosage regimens at the individual patient level, through a rational TDM approach, could prevent oncology patients from being exposed to ineffective or unnecessarily toxic drug concentrations in the era of personalized medicine.

摘要

背景

口服靶向抗癌蛋白激酶抑制剂（PKIs）在患者之间的治疗反应差异很大，其中一些药物疗效不足，另一些药物不良反应不可接受。造成这种异质性的原因有很多，例如影响血药浓度的药代动力学（PK）变异性、药物依从性波动以及癌细胞的固有或获得性耐药性。因此，需要共同努力优化这些药物的利用，以充分发挥其潜力，从而对接受 PKI 治疗的肿瘤患者进行适当的管理。

方法

对截至 2019 年 4 月 MEDLINE 上关于 PKI 的 PK、药效学和治疗药物监测（TDM）的文献进行了广泛的综述。

结果

本综述提供了确定适合 TDM 的 PKI 患者的标准（例如，分析方法的可用性、观察性 PK 研究、PK-药效学关系分析和随机对照研究）。综述了 PKI 的主要特征和局限性、TDM 对接受 PKI 治疗的癌症患者的预期益处以及适当利用 TDM 的前提条件。最后，讨论了 TDM 在支持个性化医疗时代更好地实施癌症治疗方面的各种重要实际方面和陷阱。