拥抱“优化者”项目：我们能否利用进化理论优化肿瘤学的给药剂量？
Embracing Project Optimus: Can we Leverage Evolutionary Theory to Optimize Dosing in Oncology?
机构信息
Division of Pharmacotherapy and Experimental Therapeutics, Eshelman School of Pharmacy, The University of North Carolina at Chapel Hill, 301 Pharmacy Ln, Chapel Hill, NC, 27599, USA.
Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill, 301 Pharmacy Ln, Chapel Hill, NC, 27599, USA.
出版信息
Pharm Res. 2022 Dec;39(12):3259-3265. doi: 10.1007/s11095-022-03380-1. Epub 2022 Sep 2.
Abstract
Project Optimus is a US Food and Drug Administration (FDA) initiative to reform dose selection in oncology drug development. Here, we focus on tumor evolution, a broadly observed phenomenon that invariably leads to therapeutic failure and disease relapse, and its effect on the exposure-response (E-R) relationships of oncology drugs. We propose a greater emphasis on tumor evolution during clinical development to facilitate the selection of optimal doses for molecularly targeted therapies and immunotherapies in oncology.
摘要
Optimus 计划是美国食品和药物管理局（FDA）为改革肿瘤药物开发中的剂量选择而提出的一项倡议。在这里，我们重点关注肿瘤进化，这是一种广泛观察到的现象，它不可避免地导致治疗失败和疾病复发，并对肿瘤药物的暴露-反应（E-R）关系产生影响。我们建议在临床开发过程中更加重视肿瘤进化，以促进选择最佳剂量的分子靶向治疗和肿瘤免疫治疗。
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