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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Online Access: | https://doi.org/10.1002/psp4.12415 |
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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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