SCHNEIDER, Benjamin; BOYER, Arnaud; CICCOLINI, Joseph; BARLESI, Fabrice; WANG, Kenneth; BENZEKRY, Sébastien; MOCHEL, Jonathan

doi:10.1002/psp4.12415

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SCHNEIDER, Benjamin
Iowa State University [ISU]

BOYER, Arnaud
Simulation and Modeling of Adaptive Response for Therapeutics in Cancer [SMARTc]

CICCOLINI, Joseph
Simulation and Modeling of Adaptive Response for Therapeutics in Cancer [SMARTc]

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CPT: Pharmacometrics and Systems Pharmacology. 2019-04-19

American Society for Clinical Pharmacology and Therapeutics ; International Society of Pharmacometrics

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Bevacizumab-pemetrexed/cisplatin (BEV-PEM/CIS) is a first line therapeutic for advanced non-squamous non-small cell lung cancer (NSCLC). Bevacizumab potentiates PEM/CIS cytotoxicity by inducing transient tumor vasculature normalization. BE V- 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 NSCLC-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 simulationssuggest 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.< Réduire

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Cancers

Optimization

Oncology

Pharmacokinetics-pharmacodynamics

Mathematical modeling

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

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