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

Benjamin K. Schneider; Arnaud Boyer; Joseph Ciccolini; Fabrice Barlesi; Kenneth Wang; Sebastien Benzekry; Jonathan P. Mochel

doi:10.1002/psp4.12415

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

Benjamin K. Schneider, Arnaud Boyer, Joseph Ciccolini, Fabrice Barlesi, Kenneth Wang, Sebastien Benzekry, Jonathan P. Mochel

Résultats de recherche: Contribution à un journal › Article › Revue par des pairs

7 Citations (Scopus)

Résumé

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.

langue originale	Anglais
Pages (de - à)	577-586
Nombre de pages	10
journal	CPT: Pharmacometrics and Systems Pharmacology
Volume	8
Numéro de publication	8
Les DOIs	https://doi.org/10.1002/psp4.12415
état	Publié - 1 janv. 2019
Modification externe	Oui

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10.1002/psp4.12415

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title = "Optimal Scheduling of Bevacizumab and Pemetrexed/Cisplatin Dosing in Non-Small Cell Lung Cancer",

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.",

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AU - Ciccolini, Joseph

AU - Barlesi, Fabrice

AU - Wang, Kenneth

AU - Benzekry, Sebastien

AU - Mochel, Jonathan P.

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N2 - 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.

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