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

Research output: Contribution to journal › Article › peer-review

7 Citations (Scopus)

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.

Original language	English
Pages (from-to)	577-586
Number of pages	10
Journal	CPT: Pharmacometrics and Systems Pharmacology
Volume	8
Issue number	8
DOIs	https://doi.org/10.1002/psp4.12415
Publication status	Published - 1 Jan 2019
Externally published	Yes

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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 - 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.

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

Abstract

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