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治疗药物监测在抗癌药物安全性管理中的作用:以 3 种细胞毒药物为重点。

The role of therapeutic drug monitoring in the management of safety of anticancer agents: a focus on 3 cytotoxics.

机构信息

Pharmacy, Hôpital Hautepierre , Strasbourg , France.

出版信息

Expert Opin Drug Saf. 2019 Nov;18(11):1009-1015. doi: 10.1080/14740338.2019.1662395. Epub 2019 Sep 6.

Abstract

: Therapeutic drug monitoring in oncology is used to prevent major toxicities of selected anticancer agents due to overexposure by individualizing the dose based on a pharmacokinetic target. : Numerous studies relating a relation between pharmacokinetic variability and toxicity have been reported since the eighties but very few have been implemented in clinical practice due to a lack of validation and harmonization, logistical constraints and reluctance from oncologists. Following recent recommendations, this paper highlights the current-validated applications of pharmacokinetic monitoring in oncology focusing on the safety of anticancer therapies. : Paradoxically given the oldness of the agents, guidelines of dose adjustment have been recently available for intravenous busulfan, 5-fluorouracil, and high-dose methotrexate. Interestingly, besides the enhancement of tolerability, it applies to potential curative clinical situations. In an era of personalized oncology that integrates complex molecular factors in the treatment of cancer, education is needed for oncologists to show the benefits of this valuable (even old) resource for the safety of patients. Therapeutic drug monitoring for busulfan, 5-fluorouracil and methotrexate will still hold in the future unless more active agents are available in the concerned indications.

摘要

肿瘤治疗药物监测用于通过基于药代动力学目标的个体化剂量来预防选定的抗癌药物因过度暴露而导致的主要毒性。自 80 年代以来,已经有许多研究报道了药物代谢动力学变异性与毒性之间的关系,但由于缺乏验证和协调、后勤限制以及肿瘤学家的不情愿,很少有研究在临床实践中得到实施。根据最近的建议,本文重点介绍了药代动力学监测在肿瘤学中的当前验证应用,侧重于抗癌治疗的安全性。具有讽刺意味的是,尽管这些药物的历史悠久,但最近才为静脉注射白消安、5-氟尿嘧啶和高剂量甲氨蝶呤制定了剂量调整指南。有趣的是,除了提高耐受性外,它还适用于潜在的治愈性临床情况。在个性化肿瘤学的时代,将复杂的分子因素整合到癌症的治疗中,肿瘤学家需要接受教育,以展示这种有价值的(甚至是古老的)资源对患者安全的益处。在相关适应症中,除非有更有效的药物,否则治疗药物监测仍将适用于白消安、5-氟尿嘧啶和甲氨蝶呤。

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