日本急性髓性白血病患者在接受文尼他克和阿扎胞苷治疗期间,过度暴露于文尼他克与中性粒细胞减少症持续时间延长有关。

IF 2.7 4区 医学 Q3 ONCOLOGY Cancer Chemotherapy and Pharmacology Pub Date : 2024-08-01 Epub Date: 2024-05-23 DOI:10.1007/s00280-024-04673-5
Takahiro Kobayashi, Honami Sato, Masatomo Miura, Yayoi Fukushi, Wataru Kuroki, Fumiko Ito, Kazuaki Teshima, Atsushi Watanabe, Naohito Fujishima, Isuzu Kobayashi, Yoshihiro Kameoka, Naoto Takahashi
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引用次数: 0

摘要

目的:一项观察性研究旨在评估日本急性髓性白血病(AML)患者接受文替曲克和阿扎胞苷治疗后文替曲克的药代动力学及其对疗效和安全性的影响:方法:在33例未经治疗或复发/难治性AML患者中评估了阿扎胞苷和venetoclax治疗第一周期后血浆浓度与疗效和安全性之间的关系:所有患者均接受了全剂量的 Venetoclax 治疗。82%的患者接受了为期28天的 Venetoclax 治疗;阿扎胞苷的相对剂量强度为82%。完全缓解组(CR)和血液学不完全恢复组(CRi)患者的低浓度明显高于无形态白血病状态组、部分缓解组和无应答组(P = 0.01)。3 级中性粒细胞减少症的中位持续时间为 28 天(范围为 8-46 天)。3级中性粒细胞减少持续时间较长(≥28天)的患者血药浓度曲线下面积(AUC0-24)明显高于持续时间较短的患者(0-24是中性粒细胞减少持续时间较长的显著预测因子(几率比54.3,P = 0.007)):结论:日本急性髓细胞性白血病患者血浆中的 Venetoclax 浓度各不相同。结论:日本急性髓细胞性白血病患者的血浆浓度各不相同,较高的血浆浓度与CR/CRi和持续的3级中性粒细胞减少症相关。因此,必须根据个体药代动力学数据调整 Venetoclax 的给药时间,以限制药物总暴露量、减少严重中性粒细胞减少症并获得更高的疗效。
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Overexposure to venetoclax is associated with prolonged-duration of neutropenia during venetoclax and azacitidine therapy in Japanese patients with acute myeloid leukemia.

Purpose: An observational study was conducted to evaluate the pharmacokinetics of venetoclax and its impact on the efficacy and safety for Japanese patients with acute myeloid leukemia (AML) treated with venetoclax and azacitidine therapy.

Methods: The association between the plasma concentration, after the first cycle of azacitidine and venetoclax therapy, and the efficacy and safety was evaluated in 33 patients with untreated or relapsed/refractory AML.

Results: Full dose of venetoclax was administered to all patients. Venetoclax treatment was 28 day long in 82% of patients; the relative dose intensity of azacitidine was 82%. Trough concentration was significantly higher among patients with complete remission (CR) and CR with incomplete hematologic recovery (CRi) than those with the morphologic leukemia-free state and partial remission, and no response groups (P = 0.01). Median duration of grade 3 neutropenia was 28 days (range 8-46 days). Area under the concentration-time curve (AUC0-24) was significantly higher among patients with protracted grade 3 neutropenia (≥ 28 days) than those with a shorter duration (< 28 days) (P = 0.03); multivariate analysis revealed that a higher AUC0-24 was a significant predictor of a longer duration of neutropenia (odds ratio 54.3, P = 0.007).

Conclusion: Plasma concentrations of venetoclax were variable in Japanese patients with AML. Higher plasma concentrations were associated with CR/CRi and protracted grade 3 neutropenia. Therefore, it is essential to adjust the duration of venetoclax administration based on individual pharmacokinetic data to limit total drug exposure, reduce severe neutropenia, and achieve higher efficacy.

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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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