Del Re M, Roncato R, Argentiero A, Berrino L, Botticelli A, Capuano A, Di Donato S, Fogli S, Marino D, Rodriquenz G, Speranza D, Perrone F, Silvestris N, Danesi R
Saint Camillus International University of Health and Medical Sciences, Departmental Faculty of Medicine, Rome, Italy.
Department of Medicine, University of Udine, Udine, Italy.
ESMO Open. 2025 Jun;10(6):105119. doi: 10.1016/j.esmoop.2025.105119. Epub 2025 Jun 10.
Drug-drug interactions (DDIs) are a critical challenge in managing cancer patients receiving polytherapy, often due to comorbid conditions. DDIs can arise through pharmacokinetic mechanisms, affecting drug absorption, distribution, metabolism, or excretion, or through pharmacodynamic interactions, altering drug target binding or leading to overlapping toxicities. These interactions can compromise treatment efficacy, exacerbate adverse events, and increase patient morbidity and mortality.
Effective DDI management requires a multidisciplinary approach that integrates oncologists and pharmacologists. Key factors influencing DDIs include the pharmacological properties of drugs, patient-specific clinical and genetic characteristics, and the timing of therapy exposure. Identifying and mitigating DDIs also relies on patients' adherence to treatment and their early reporting of adverse events.
This article proposes a structured framework for DDI assessment in oncology, emphasizing actionable strategies tailored to the complexities of cancer care. The framework incorporates the evaluation of pharmacokinetic and pharmacodynamic interactions, identification of high-risk drug combinations, and the use of therapeutic drug monitoring (TDM) and pharmacogenetics to individualize treatment. Specific recommendations for managing QTc-prolonging interactions, CYP3A4-mediated metabolism, and P-glycoprotein (P-gp)-related transport issues are highlighted.
By fostering collaboration among health care professionals and leveraging advanced tools, the proposed approach aims to optimize therapeutic outcomes while minimizing DDI risks. The manuscript underscores the importance of tailored strategies in oncology, advocating for the integration of pharmacological insights into clinical practice to enhance patient safety and treatment efficacy.
药物相互作用（DDIs）是管理接受多种疗法的癌症患者时面临的一项关键挑战，这通常是由于合并症所致。药物相互作用可通过药代动力学机制产生，影响药物的吸收、分布、代谢或排泄，或通过药效学相互作用，改变药物靶点结合或导致毒性重叠。这些相互作用会损害治疗效果，加重不良事件，并增加患者的发病率和死亡率。
有效的药物相互作用管理需要肿瘤学家和药理学家整合的多学科方法。影响药物相互作用的关键因素包括药物的药理学特性、患者特定的临床和遗传特征以及治疗暴露的时间。识别和减轻药物相互作用还依赖于患者对治疗的依从性及其对不良事件的早期报告。
本文提出了一个肿瘤学中药物相互作用评估的结构化框架，强调针对癌症护理复杂性量身定制的可操作策略。该框架纳入了药代动力学和药效学相互作用的评估、高风险药物组合的识别，以及使用治疗药物监测（TDM）和药物遗传学来实现个体化治疗。重点突出了管理QTc延长相互作用、CYP3A4介导的代谢和P-糖蛋白（P-gp）相关转运问题的具体建议。
通过促进医疗保健专业人员之间的合作并利用先进工具，所提出的方法旨在优化治疗结果，同时将药物相互作用风险降至最低。该手稿强调了肿瘤学中量身定制策略的重要性，倡导将药理学见解整合到临床实践中，以提高患者安全性和治疗效果。
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