Risk factors associated with high-dose methotrexate induced toxicities.

Wenshu Li, Jiayi Mo, Zhilin Yang, Zhigang Zhao, Shenghui Mei
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Abstract

Introduction: High-dose methotrexate (HDMTX) therapy poses challenges in various neoplasms due to individualized pharmacokinetics and associated adverse effects. Our purpose is to identify early risk factors associated with HDMTX-induced toxicities, paving the way for personalized treatment.

Areas covered: A systematic review of PubMed and Cochrane databases was conducted for articles from inception to July 2023. Eligible studies included reviews, clinical trials, and real-world analyses. Irrelevant studies were excluded, and manual searches and citation reviews were performed. Factors such as MTX exposure, drug interactions, demographics, serum albumin, urine pH, serum calcium, and genetic polymorphisms affecting MTX transport (e.g. SLCO1B1), intracellular folate metabolism (MTHFR), cell development (ARID5B), metabolic pathways (UGT1A1, PNPLA3), as well as epigenetics were identified.

Expert opinion: This comprehensive review aids researchers and clinicians in early identification of HDMTX toxicity risk factors. By understanding the multifaceted risk factors associated with hematologic malignancies, personalized treatment approaches can be tailored to optimize therapeutic outcomes.

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与大剂量甲氨蝶呤引起的毒性相关的风险因素。
简介:大剂量甲氨蝶呤(HDMTX)疗法因其个体化的药代动力学和相关不良反应,给各种肿瘤的治疗带来了挑战。我们的目的是确定与 HDMTX 引起的毒性相关的早期风险因素,为个性化治疗铺平道路:对 PubMed 和 Cochrane 数据库中从开始到 2023 年 7 月的文章进行了系统性回顾。符合条件的研究包括综述、临床试验和真实世界分析。排除了不相关的研究,并进行了人工检索和引文回顾。确定了 MTX 暴露、药物相互作用、人口统计学、血清白蛋白、尿 pH 值、血清钙、影响 MTX 转运(如 SLCO1B1)、细胞内叶酸代谢(MTHFR)、细胞发育(ARID5B)、代谢途径(UGT1A1、PNPLA3)以及表观遗传学的基因多态性等因素:本综述有助于研究人员和临床医生及早识别HDMTX毒性风险因素。通过了解与血液恶性肿瘤相关的多方面风险因素,可以定制个性化治疗方法,优化治疗效果。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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