Optimal Scheduling of Bevacizumab and Pemetrexed/cisplatin Dosing in Non‐Small Cell Lung Cancer
BARLESI, Fabrice
Service d'oncologie multidisciplinaire innovations thérapeutiques [Hôpital Nord - APHM]
Service d'oncologie multidisciplinaire innovations thérapeutiques [Hôpital Nord - APHM]
BENZEKRY, Sébastien
Modélisation Mathématique pour l'Oncologie [MONC]
Institut de Mathématiques de Bordeaux [IMB]
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Modélisation Mathématique pour l'Oncologie [MONC]
Institut de Mathématiques de Bordeaux [IMB]
Language
en
Article de revue
This item was published in
CPT: Pharmacometrics and Systems Pharmacology. 2019-04-19
American Society for Clinical Pharmacology and Therapeutics ; International Society of Pharmacometrics
English 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 ...Read more >
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.Read less <
English Keywords
Cancers
Optimization
Oncology
Pharmacokinetics-pharmacodynamics
Mathematical modeling
Origin
Hal imported