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氟嘧啶诱导的毒性与二氢嘧啶脱氢酶缺乏症:一例早期发生的致命性卡培他滨诱导毒性病例报告及文献综述。三醋酸尿苷:作为解毒剂的疗效与安全性。在美国以外地区是否可获取?

Fluoropyrimidine-induced toxicity and DPD deficiency.. A case report of early onset, lethal capecitabine-induced toxicity and mini review of the literature. Uridine triacetate: Efficacy and safety as an antidote. Is it accessible outside USA?

作者信息

Lampropoulou Dimitra Ioanna, Laschos Konstantinos, Amylidi Anna-Lea, Angelaki Ariadni, Soupos Nikolaos, Boumpoucheropoulos Sotirios, Papadopoulou Eirini, Nanou Evgenia, Zidianakis Vasilios, Nasioulas George, Fildissis George, Aravantinos Gerasimos

机构信息

Second Department of Medical Oncology, General Oncology Hospital of Kifissia "Agioi Anargiroi", Athens, Greece.

GeneKor Medical SA, Athens, Greece.

出版信息

J Oncol Pharm Pract. 2020 Apr;26(3):747-753. doi: 10.1177/1078155219865597. Epub 2019 Aug 5.

Abstract

Fluoropyrimidine-based regimens are among the most commonly used chemotherapy combinations for the treatment of solid tumors. Several genetic polymorphisms that are implicated with fluoropyrimidine anabolism and catabolism have been associated with the development of life-threatening toxicities. Uridine triacetate is an FDA-approved antidote for 5-fluorouracil or capecitabine overdose and early-onset, life-threatening toxicity within 96 h of last chemotherapy dose. To date, it is not accessible for Greek patients as per the current summary of product characteristic's time restrictions. We report and discuss the course and outcome of capecitabine toxicity in a 66-year-old female colorectal cancer patient with heterozygous dihydropyrimidine dehydrogenase deficiency. This paper highlights the difficulty in timely access of this lifesaving medication for Greek and possibly other European patients.

摘要

基于氟嘧啶的治疗方案是治疗实体瘤最常用的化疗组合之一。一些与氟嘧啶合成代谢和分解代谢相关的基因多态性与危及生命的毒性反应的发生有关。三乙酸尿苷是一种经美国食品药品监督管理局批准的解毒剂,用于治疗5-氟尿嘧啶或卡培他滨过量以及在上次化疗剂量后96小时内出现的早发性、危及生命的毒性反应。迄今为止,根据目前产品特性总结中的时间限制,希腊患者无法获得该药物。我们报告并讨论了一名66岁女性结直肠癌患者因二氢嘧啶脱氢酶杂合子缺乏导致卡培他滨毒性反应的过程及结果。本文强调了希腊及其他可能的欧洲患者及时获得这种救命药物的困难。

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