为预测成年血液系统恶性肿瘤患者在使用大剂量甲氨蝶呤后的甲氨蝶呤延迟排泄量而开发的新型提名图。

IF 2.7 4区 医学 Q3 ONCOLOGY Cancer Chemotherapy and Pharmacology Pub Date : 2024-09-01 Epub Date: 2024-06-21 DOI:10.1007/s00280-024-04687-z
Daisuke Ikeda, Tatsuya Isezaki, Kentaro Narita, Satoshi Yuyama, Mitsuaki Oura, Atsushi Uehara, Rikako Tabata, Masami Takeuchi, Kosei Matsue
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引用次数: 0

摘要

目的:大剂量甲氨蝶呤(HDMTX)是治疗血液系统恶性肿瘤不可或缺的药物,但由于MTX暴露时间过长,存在严重毒性的风险。然而,有关MTX排泄延迟的知识主要来自儿科和青少年队列,所报告的预测因素均为粗略的二分法值。本研究旨在确定血液恶性肿瘤成人患者MTX排泄延迟的风险因素,并根据连续的临床和实验室变量制定更适用的预测提名图。方法:对194名患者的517个HDMTX周期进行了回顾性分析。MTX延迟排泄的定义是:开始使用HDMTX后48小时内MTX浓度≥1.0 µmol/L或72小时内MTX浓度≥0.1 µmol/L。多变量逻辑回归分析用于构建提名图,并通过引导法进行了内部验证:24.0%的周期观察到MTX排泄延迟。结果:在 24.0% 的周期中观察到 MTX 排泄延迟,发现了六个重要的预测因素:复发/难治性疾病(Odds ratio [OR] 2.03)、较少的 HDMTX 周期(OR 0.771)、治疗意图(OR 2.13)、较低的白蛋白(OR 0.563)和肌酐清除率水平(OR 0.993)以及γ-谷氨酰转肽酶水平升高(OR 1.004,均为 P):本研究全面描述了成年患者在接受 HDMTX 治疗后 MTX 清除失败的特征,可为个体化风险预测铺平道路。
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Development of a novel nomogram for predicting delayed methotrexate excretion following high-dose methotrexate in adult patients with hematologic malignancies.

Purpose: High-dose methotrexate (HDMTX) is integral in treating hematologic malignancies but carries risks of severe toxicities due to prolonged MTX exposure. However, knowledge of delayed MTX excretion is primarily derived from pediatric and adolescent cohorts, with the reported predictors being presented as rough dichotomous values. This study aimed to identify risk factors for delayed MTX excretion exclusively in adult patients with hematologic malignancies and develop a more applicable predictive nomogram based on continuous clinical and laboratory variables.

Methods: 517 HDMTX cycles in 194 patients were retrospectively analyzed. Delayed MTX excretion was defined as either MTX concentration ≥ 1.0 µmol/L at 48 h or ≥ 0.1 µmol/L at 72 h after HDMTX initiation. Multivariate logistic regression analysis was used to construct the nomogram internally validated with the bootstrap method.

Results: Delayed MTX excretion was observed in 24.0% of cycles. Six significant predictors were identified: relapsed/refractory disease (Odds ratio [OR] 2.03), fewer HDMTX cycles (OR 0.771), treatment intent (OR 2.13), lower albumin (OR 0.563) and creatinine clearance levels (OR 0.993), and increased γ-glutamyl transpeptidase levels (OR 1.004, all P < 0.05). These were incorporated into a web-based nomogram as continuous variables with good prediction accuracy (area under the curve, 0.73) and without significant overfitting. Delayed MTX excretion increased risks of developing acute kidney injury, even solely at the 72 h timepoint (OR 2.57, P = 0.025), without providing any benefit of clinical outcomes.

Conclusion: This study comprehensively characterized MTX elimination failure following HDMTX in adult patients and could pave the way for individualized risk prediction.

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来源期刊
CiteScore
6.10
自引率
3.30%
发文量
116
审稿时长
2.5 months
期刊介绍: Addressing a wide range of pharmacologic and oncologic concerns on both experimental and clinical levels, Cancer Chemotherapy and Pharmacology is an eminent journal in the field. The primary focus in this rapid publication medium is on new anticancer agents, their experimental screening, preclinical toxicology and pharmacology, single and combined drug administration modalities, and clinical phase I, II and III trials. It is essential reading for pharmacologists and oncologists giving results recorded in the following areas: clinical toxicology, pharmacokinetics, pharmacodynamics, drug interactions, and indications for chemotherapy in cancer treatment strategy.
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