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 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.
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Submitted on : Wednesday, April 24, 2019 - 6:31:42 PM
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Benjamin Schneider, Arnaud Boyer, Joseph Ciccolini, Fabrice Barlési, Kenneth Wang, et al.. Optimal Scheduling of Bevacizumab and Pemetrexed/cisplatin Dosing in Non‐Small Cell Lung Cancer. CPT: Pharmacometrics and Systems Pharmacology, American Society for Clinical Pharmacology and Therapeutics ; International Society of Pharmacometrics, 2019, ⟨10.1002/psp4.12415⟩. ⟨hal-02109335⟩

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