Jacob Aasems, Sekkath Veedu Janeesh, Selene Insija, Raj Rishi, Kannan Lakshmi, Patel Reema
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.
Front Pharmacol. 2022 Sep 7;13:977734. doi: 10.3389/fphar.2022.977734. eCollection 2022.
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.
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。