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

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

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 attract...

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Main Authors: Benjamin K. Schneider, Arnaud Boyer, Joseph Ciccolini, Fabrice Barlesi, Kenneth Wang, Sebastien Benzekry, Jonathan P. Mochel
Format: Article
Language:English
Published: Wiley 2019-08-01
Series:CPT: Pharmacometrics & Systems Pharmacology
Online Access:https://doi.org/10.1002/psp4.12415
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spelling doaj-c4e1e6e054b64c4bac781ea1ff5402472020-11-25T01:29:40ZengWileyCPT: Pharmacometrics & Systems Pharmacology2163-83062019-08-018857758610.1002/psp4.12415Optimal Scheduling of Bevacizumab and Pemetrexed/Cisplatin Dosing in Non‐Small Cell Lung CancerBenjamin K. Schneider0Arnaud Boyer1Joseph Ciccolini2Fabrice Barlesi3Kenneth Wang4Sebastien Benzekry5Jonathan P. Mochel6Iowa State University College of Veterinary Medicine Ames Iowa USASMARTc Unit Centre de Recherche en Cancérologie de Marseille Unité Mixte de Recherche (UMR) Inserm U1068 Aix Marseille University Marseille FranceSMARTc Unit Centre de Recherche en Cancérologie de Marseille Unité Mixte de Recherche (UMR) Inserm U1068 Aix Marseille University Marseille FranceMultidisciplinary Oncology and Therapeutic Innovations Department Assistance Publique Hôpitaux de Marseille Marseille FranceMayo Clinic Rochester Minnesota USAIowa State University College of Veterinary Medicine Ames Iowa USAIowa State University College of Veterinary Medicine Ames Iowa USABevacizumab‐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.https://doi.org/10.1002/psp4.12415
collection DOAJ
language English
format Article
sources DOAJ
author Benjamin K. Schneider
Arnaud Boyer
Joseph Ciccolini
Fabrice Barlesi
Kenneth Wang
Sebastien Benzekry
Jonathan P. Mochel
spellingShingle Benjamin K. Schneider
Arnaud Boyer
Joseph Ciccolini
Fabrice Barlesi
Kenneth Wang
Sebastien Benzekry
Jonathan P. Mochel
Optimal Scheduling of Bevacizumab and Pemetrexed/Cisplatin Dosing in Non‐Small Cell Lung Cancer
CPT: Pharmacometrics & Systems Pharmacology
author_facet Benjamin K. Schneider
Arnaud Boyer
Joseph Ciccolini
Fabrice Barlesi
Kenneth Wang
Sebastien Benzekry
Jonathan P. Mochel
author_sort Benjamin K. Schneider
title Optimal Scheduling of Bevacizumab and Pemetrexed/Cisplatin Dosing in Non‐Small Cell Lung Cancer
title_short Optimal Scheduling of Bevacizumab and Pemetrexed/Cisplatin Dosing in Non‐Small Cell Lung Cancer
title_full Optimal Scheduling of Bevacizumab and Pemetrexed/Cisplatin Dosing in Non‐Small Cell Lung Cancer
title_fullStr Optimal Scheduling of Bevacizumab and Pemetrexed/Cisplatin Dosing in Non‐Small Cell Lung Cancer
title_full_unstemmed Optimal Scheduling of Bevacizumab and Pemetrexed/Cisplatin Dosing in Non‐Small Cell Lung Cancer
title_sort optimal scheduling of bevacizumab and pemetrexed/cisplatin dosing in non‐small cell lung cancer
publisher Wiley
series CPT: Pharmacometrics & Systems Pharmacology
issn 2163-8306
publishDate 2019-08-01
description 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.
url https://doi.org/10.1002/psp4.12415
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