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1
Use of Uridine Triacetate to Reverse Severe Persistent Myelosuppression Following 5-fluorouracil Exposure in a Patient With a c.557A>G Heterozygous DPYD Variant.在一名携带c.557A>G杂合DPYD变异的患者中,使用尿苷三乙酸逆转5-氟尿嘧啶暴露后的严重持续性骨髓抑制。
Clin Colorectal Cancer. 2021 Sep;20(3):273-278. doi: 10.1016/j.clcc.2021.03.002. Epub 2021 Apr 6.
2
Hyperammonemic encephalopathy during XELOX regimen. Is it capecitabine or oxaliplatin responsible?XELOX 方案治疗期间发生高氨血症性脑病。是卡培他滨还是奥沙利铂引起的?
Anticancer Drugs. 2020 Nov;31(10):1103-1105. doi: 10.1097/CAD.0000000000000987.
3
North American Congress of Clinical Toxicology (NACCT) Abstracts 2019.2019年北美临床毒理学大会(NACCT)摘要
Clin Toxicol (Phila). 2019 Oct;57(10):870-1052. doi: 10.1080/15563650.2019.1636569. Epub 2019 Jul 24.
4
Uridine triacetate for severe 5-fluorouracil toxicity in a patient with thymidylate synthase gene variation: Potential pharmacogenomic implications.尿苷三乙酸用于治疗胸苷酸合成酶基因变异患者的严重5-氟尿嘧啶毒性:潜在的药物基因组学意义。
SAGE Open Med Case Rep. 2018 Jul 4;6:2050313X18786405. doi: 10.1177/2050313X18786405. eCollection 2018.
5
Successful use of uridine triacetate (Vistogard) three weeks after capecitabine in a patient with homozygous dihydropyrimidine dehydrogenase mutation: A case report and review of the literature.一名纯合二氢嘧啶脱氢酶突变患者在卡培他滨治疗三周后成功使用三醋酸尿苷(Vistogard):病例报告及文献综述
J Oncol Pharm Pract. 2019 Jan;25(1):234-238. doi: 10.1177/1078155217732141. Epub 2017 Sep 26.
6
Acute hyperammonemic encephalopathy after fluoropyrimidine-based chemotherapy: A case series and review of the literature.氟尿嘧啶类化疗后急性高氨血症性脑病:病例系列及文献综述
Medicine (Baltimore). 2017 Jun;96(22):e6874. doi: 10.1097/MD.0000000000006874.
7
The successful treatment of 5-fluorouracil (5-FU) overdose in a patient with malignancy and HIV/AIDS with uridine triacetate.使用三乙酸尿苷成功治疗一名患有恶性肿瘤及HIV/AIDS的患者的5-氟尿嘧啶(5-FU)过量中毒。
Am J Emerg Med. 2017 May;35(5):802.e7-802.e8. doi: 10.1016/j.ajem.2016.11.038. Epub 2016 Nov 15.
8
Emergency use of uridine triacetate for the prevention and treatment of life-threatening 5-fluorouracil and capecitabine toxicity.尿苷三乙酸酯在预防和治疗危及生命的5-氟尿嘧啶和卡培他滨毒性中的紧急使用。
Cancer. 2017 Jan 1;123(2):345-356. doi: 10.1002/cncr.30321. Epub 2016 Sep 13.
9
FDA Approval: Uridine Triacetate for the Treatment of Patients Following Fluorouracil or Capecitabine Overdose or Exhibiting Early-Onset Severe Toxicities Following Administration of These Drugs.FDA 批准:三乙酸尿苷用于氟尿嘧啶或卡培他滨用药过量的患者,或这些药物给药后出现早期严重毒性的患者。
Clin Cancer Res. 2016 Sep 15;22(18):4545-9. doi: 10.1158/1078-0432.CCR-16-0638. Epub 2016 Jul 11.
10
Irreversible cerebellar toxicity after infusional 5-flurouracil therapy.输注5-氟尿嘧啶治疗后不可逆的小脑毒性。
Indian J Cancer. 2015 Oct-Dec;52(4):627-8. doi: 10.4103/0019-509X.178423.

病例报告:三乙酸尿苷治疗5-氟尿嘧啶延迟性毒性:一例病例报告及文献综述

Case report: Uridine triacetate in the management of delayed onset 5-fluorouracil toxicity: A case report and review of literature.

作者信息

Jacob Aasems, Sekkath Veedu Janeesh, Selene Insija, Raj Rishi, Kannan Lakshmi, Patel Reema

机构信息

Department of Hematology and Oncology, Pikeville Medical Center, Pikeville, KY, United States.

Division of Medical Oncology, Department of Internal Medicine, University of Kentucky, Lexington, KY, United States.

出版信息

Front Pharmacol. 2022 Sep 7;13:977734. doi: 10.3389/fphar.2022.977734. eCollection 2022.

DOI:10.3389/fphar.2022.977734
PMID:36160401
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9490183/
Abstract

5-fluorouracil (5FU) and capecitabine are fluoropyrimidine anti-neoplastic drugs commonly used in the treatment of different types of cancer. Hereditary dihydropyrimdine deaminase (DPD), thymidylate synthase mutations and drug overdose may lead to life-threatening toxicities. Uridine triacetate (UTA) is an emergency treatment for overdoses and early onset, severe or life-threatening toxicities from fluoropyrimidines. It is approved for use in adults and children within 96 h of last fluoropyrimidine administration. We present the case of a 64-year-old male treated with 5-FU and oxaliplatin as adjuvant systemic therapy for stage IIIA rectal cancer who developed delayed central nervous system toxicity 18 days after initiating chemotherapy. He had rapidly worsening encephalopathy and ataxia. Laboratory workups, MRI brain and EEG were negative. He was started on UTA with concerns of 5-FU toxicity due to the life-threatening nature of his condition even beyond the recommended 96-h time cut-off. He had rapid improvement in clinical status and resolution of encephalopathy. DPD deficiency testing later resulted as heterozygous for IVS14+1G>A allele indicating enzyme deficiency. This report demonstrates the importance of identifying delayed side effects with fluoropyrimidine therapy and potential treatment for reversing these effects. We also did an extensive literature review and obtained reports from the uridine triacetate clinical trials on patients receiving UTA after the 96-h cut-off. Based on our experience and previous published reports, a patient developing life-threatening delayed 5-FU toxicity should also be considered for UTA on a case-by-case basis.

摘要

5-氟尿嘧啶(5FU)和卡培他滨是常用于治疗不同类型癌症的氟嘧啶类抗肿瘤药物。遗传性二氢嘧啶脱氨酶(DPD)、胸苷酸合成酶突变及药物过量可能导致危及生命的毒性反应。尿苷三乙酸(UTA)是针对氟嘧啶类药物过量以及早期发生的严重或危及生命毒性反应的一种急救治疗方法。它被批准用于在最后一次给予氟嘧啶类药物后96小时内的成人和儿童。我们报告了一例64岁男性患者,其接受5-FU和奥沙利铂作为ⅢA期直肠癌的辅助全身治疗,在开始化疗18天后出现延迟性中枢神经系统毒性反应。他的脑病和共济失调迅速加重。实验室检查、脑部MRI和脑电图均为阴性。鉴于其病情危及生命,即使超出了推荐的96小时时间界限,考虑到5-FU毒性,开始对他使用UTA治疗。他的临床状况迅速改善,脑病症状消退。后来的DPD缺乏检测结果显示IVS14 +1G>A等位基因杂合,表明存在酶缺乏。本报告证明了识别氟嘧啶类治疗延迟副作用以及逆转这些影响的潜在治疗方法的重要性。我们还进行了广泛的文献综述,并获取了来自尿苷三乙酸临床试验中96小时时间界限后接受UTA治疗患者的报告。基于我们的经验和先前发表的报告,对于出现危及生命的延迟性5-FU毒性反应的患者,也应逐案考虑使用UTA治疗。