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优化剂量:非小细胞肺癌精准医学的下一步。

Optimized Dosing: The Next Step in Precision Medicine in Non-Small-Cell Lung Cancer.

机构信息

Department of Pharmacy and Pharmacology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands.

Department of Thoracic Oncology, The Netherlands Cancer Institute-Antoni van Leeuwenhoek, Amsterdam, The Netherlands.

出版信息

Drugs. 2022 Jan;82(1):15-32. doi: 10.1007/s40265-021-01654-3. Epub 2021 Dec 11.

Abstract

In oncology, and especially in the treatment of non-small-cell lung cancer (NSCLC), dose optimization is often a neglected part of precision medicine. Many drugs are still being administered in "one dose fits all" regimens or based on parameters that are often only minor determinants for systemic exposure. These dosing approaches often introduce additional pharmacokinetic variability and do not add to treatment outcomes. Fortunately, pharmacological knowledge is increasing, providing valuable information regarding the potential of, for example, therapeutic drug monitoring. This article focuses on the evidence for the most promising and easily implemented optimized dosing approaches for the small-molecule inhibitors, chemotherapeutic agents, and monoclonal antibodies as treatment options currently approved for NSCLC. Despite limitations such as investigations having been conducted in oncological diseases other than NSCLC or the retrospective origin of many analyses, an alternative dosing regimen could be beneficial for treatment outcomes, prescriber convenience, or financial burden on healthcare systems. This review of the literature provides recommendations on the implementation of dose optimization and advice regarding promising strategies that deserve further research in NSCLC.

摘要

在肿瘤学领域,尤其是在非小细胞肺癌(NSCLC)的治疗中,剂量优化往往是精准医学中被忽视的一部分。许多药物仍按照“一刀切”的方案给药,或基于通常只是全身暴露次要决定因素的参数。这些给药方法常常引入额外的药代动力学变异性,对治疗结果没有帮助。幸运的是,药理学知识不断增加,为例如治疗药物监测的潜力提供了有价值的信息。本文重点介绍了目前批准用于 NSCLC 的小分子抑制剂、化疗药物和单克隆抗体等治疗选择的最有前途和易于实施的优化给药方法的证据。尽管存在一些局限性,例如研究是在非 NSCLC 肿瘤学疾病中进行的,或者许多分析的来源是回顾性的,但替代给药方案可能对治疗结果、处方便利性或医疗保健系统的经济负担有益。本文对文献的综述提供了关于剂量优化实施的建议,并就值得在 NSCLC 中进一步研究的有前途的策略提供了建议。

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