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多西他赛联合聚乙二醇化重组人尿酸酶在非小细胞肺癌患者中的安全性和药代动力学。

Safety and pharmacokinetics of docetaxel in combination with pegvorhyaluronidase alfa in patients with non-small cell lung cancer.

机构信息

Halozyme Therapeutics, Inc., San Diego, California, USA.

University of Rochester Medical Center, Rochester, New York, USA.

出版信息

Clin Transl Sci. 2021 Sep;14(5):1875-1885. doi: 10.1111/cts.13041. Epub 2021 Jul 30.

Abstract

This open-label, phase Ib study (NCT02346370) assessed the effect of pegvorhyaluronidase alfa (PVHA; PEGPH20) on the plasma pharmacokinetics (PKs) and safety of docetaxel in 15 patients with stage IIIB/IV non-small cell lung cancer (NSCLC). The docetaxel PK profile from this study was consistent with simulations from a published docetaxel population PK model, and did not demonstrate an effect of PVHA on docetaxel PK. A maximum a posteriori Bayesian fit of the literature PK model to the docetaxel PK appeared unbiased. Adverse events (AEs) were generally consistent with previous reports for docetaxel monotherapy in NSCLC, except for higher incidence of musculoskeletal events, including myalgias, with PVHA plus docetaxel. The most common AEs were fatigue (87%), muscle spasms (60%), and myalgia (53%). Four patients experienced thromboembolic events (27%), three leading to treatment discontinuation. PVHA appeared to demonstrate an acceptable safety profile when given with docetaxel without significantly changing the plasma PK of docetaxel in patients with stage IIIB/IV NSCLC.

摘要

这项开放标签、Ib 期研究(NCT02346370)评估了 PEGPH20(pegvorhyaluronidase alfa,PVHA)对 15 例 IIIB/IV 期非小细胞肺癌(NSCLC)患者紫杉醇体内药代动力学(PK)和安全性的影响。本研究中的紫杉醇 PK 特征与已发表的紫杉醇群体 PK 模型模拟结果一致,且未显示 PVHA 对紫杉醇 PK 的影响。文献 PK 模型对紫杉醇 PK 的最大后验贝叶斯拟合似乎无偏倚。除了肌肉骨骼事件(包括肌痛)发生率较高外,AE 通常与 NSCLC 中紫杉醇单药治疗的先前报告一致,包括肌肉痉挛、PVHA 联合紫杉醇。最常见的 AE 是疲劳(87%)、肌肉痉挛(60%)和肌痛(53%)。4 名患者发生血栓栓塞事件(27%),其中 3 例导致治疗中断。在 IIIB/IV 期 NSCLC 患者中,当与紫杉醇联合使用时,PVHA 似乎表现出可接受的安全性特征,而不会显著改变紫杉醇的血浆 PK。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb3a/8504814/036e25dbf0f4/CTS-14-1875-g001.jpg

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