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贝伐珠单抗与培美曲塞/顺铂给药的非小细胞肺癌最佳时间安排。

Optimal Scheduling of Bevacizumab and Pemetrexed/Cisplatin Dosing in Non-Small Cell Lung Cancer.

机构信息

Iowa State University College of Veterinary Medicine, Ames, Iowa, USA.

SMARTc Unit, Centre de Recherche en Cancérologie de Marseille Unité Mixte de Recherche (UMR) Inserm U1068, Aix Marseille University, Marseille, France.

出版信息

CPT Pharmacometrics Syst Pharmacol. 2019 Aug;8(8):577-586. doi: 10.1002/psp4.12415. Epub 2019 May 9.

DOI:10.1002/psp4.12415
PMID:31004380
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6709425/
Abstract

Bevacizumab-pemetrexed/cisplatin (BEV-PEM/CIS) is a first-line therapeutic for advanced nonsquamous non-small cell lung cancer. Bevacizumab potentiates PEM/CIS cytotoxicity by inducing transient tumor vasculature normalization. BEV-PEM/CIS has a narrow therapeutic window. Therefore, it is an attractive target for administration schedule optimization. The present study leverages our previous work on BEV-PEM/CIS pharmacodynamic modeling in non-small cell lung cancer-bearing mice to estimate the optimal gap in the scheduling of sequential BEV-PEM/CIS. We predicted the optimal gap in BEV-PEM/CIS dosing to be 2.0 days in mice and 1.2 days in humans. Our simulations suggest that the efficacy loss in scheduling BEV-PEM/CIS at too great of a gap is much less than the efficacy loss in scheduling BEV-PEM/CIS at too short of a gap.

摘要

贝伐珠单抗-培美曲塞/顺铂（BEV-PEM/CIS）是晚期非鳞状非小细胞肺癌的一线治疗药物。贝伐珠单抗通过诱导肿瘤血管短暂正常化来增强 PEM/CIS 的细胞毒性。BEV-PEM/CIS 的治疗窗口较窄。因此，它是给药方案优化的一个有吸引力的目标。本研究利用我们之前在非小细胞肺癌荷瘤小鼠中进行的 BEV-PEM/CIS 药效动力学建模工作，来估计序贯 BEV-PEM/CIS 给药方案中最佳的间隔时间。我们预测 BEV-PEM/CIS 给药的最佳间隔时间在小鼠中为 2.0 天，在人体中为 1.2 天。我们的模拟表明，在太大的间隔时间安排 BEV-PEM/CIS 会导致疗效损失，远小于在太短的间隔时间安排 BEV-PEM/CIS 会导致的疗效损失。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0dc3/6709425/afb1617f6d86/PSP4-8-577-g005.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0dc3/6709425/cfb853421ae0/PSP4-8-577-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0dc3/6709425/3375ff09d47c/PSP4-8-577-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0dc3/6709425/0a5994680f3d/PSP4-8-577-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0dc3/6709425/c22c6ba0b6b2/PSP4-8-577-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0dc3/6709425/afb1617f6d86/PSP4-8-577-g005.jpg

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