Fort-Casamartina Eduard, Pernas Sonia, Otero Sara, Mate Paula, Gonzalo Núria, Narváez Sonia, Rigo-Bonnin Raúl, Padró-Miquel Ariadna, Teulé Àlex, Garcia Del Muro Xavier, Peiró Inma, Arribas Lorena, Esteve Anna, Gonzalez Andrea, Rey Montse, Clopés Ana, Fontanals Sandra, Muñoz Carme
Pharmacy Department, Institut Català Oncologia (ICO), Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), L'Hospitalet Llobregat, 08908 Barcelona, Spain.
Medical Oncology Department, Institut Català Oncologia (ICO), Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), L'Hospitalet Llobregat, 08908 Barcelona, Spain.
J Clin Med. 2024 Dec 30;14(1):145. doi: 10.3390/jcm14010145.
Everolimus, an oral inhibitor of the mammalian target of rapamycin (mTOR), is actually used to prevent organ transplant rejection and treat metastatic breast, renal, and neuroendocrine cancers. Despite significant pharmacokinetic variability among patients, routine therapeutic drug monitoring (TDM) is not commonly used in oncology. The aim of this multicenter, prospective observational cohort study is to assess the prevalence of everolimus minimum concentration at a steady state (Cminss) falling outside the therapeutic range (10-26.3 ng/mL) during a routine TDM programme. Sixty patients with metastatic breast, neuroendocrine, or renal cancers, either starting or continuing everolimus treatment according to hospital protocols, are to be included between 1st of January 2024 and 31st of December 2025 (patients undergoing clinical trials are excluded). We hypothesize that 30-50% of our patients and their blood samples will not achieve the target optimal plasma concentrations. Blood samples are collected every 4-6 weeks to monitor drug levels. The secondary goal is to explore correlation between out-of-range everolimus levels and factors such as demographic and anthropometric data, treatment specifics, lab results, genetic polymorphisms, and the presence of toxicity. This study could offer valuable insights into optimizing dosing strategies and may contribute to future research on personalizing everolimus and other anticancer treatments. This personalized approach seeks to tailor therapy not only to the tumour's molecular profile but also to the individual characteristics of each patient, improving both drug selection and dosing precision.
依维莫司是一种口服的哺乳动物雷帕霉素靶蛋白（mTOR）抑制剂，实际用于预防器官移植排斥反应以及治疗转移性乳腺癌、肾癌和神经内分泌癌。尽管患者之间存在显著的药代动力学变异性，但肿瘤学中并不常用常规治疗药物监测（TDM）。这项多中心、前瞻性观察性队列研究的目的是评估在常规TDM计划期间，依维莫司稳态最低浓度（Cminss）落在治疗范围（10 - 26.3 ng/mL）之外的发生率。2024年1月1日至2025年12月31日期间，将纳入60例根据医院方案开始或继续接受依维莫司治疗的转移性乳腺癌、神经内分泌癌或肾癌患者（正在进行临床试验的患者被排除）。我们假设30% - 50%的患者及其血样无法达到目标最佳血浆浓度。每4 - 6周采集血样以监测药物水平。次要目标是探讨依维莫司水平超出范围与人口统计学和人体测量数据、治疗细节、实验室结果、基因多态性以及毒性存在等因素之间的相关性。这项研究可为优化给药策略提供有价值的见解，并可能有助于未来关于依维莫司及其他抗癌治疗个性化的研究。这种个性化方法不仅旨在根据肿瘤的分子特征，还根据每位患者的个体特征来调整治疗方案，提高药物选择和给药精度。
