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CPT Pharmacometrics Syst Pharmacol. 2019 Apr 19. doi: 10.1002/psp4.12415. [Epub ahead of print]

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

Author information

1
Iowa State University College of Veterinary Medicine, Ames, Iowa, USA.
2
SMARTc Unit, Centre de Recherche en Cancérologie de Marseille Unité Mixte de Recherche (UMR) Inserm U1068, Aix Marseille University, Marseille, France.
3
Multidisciplinary Oncology and Therapeutic Innovations Department, Assistance Publique Hôpitaux de Marseille, Marseille, France.
4
Mayo Clinic, Rochester, Minnesota, USA.
5
Team Modelisation en Oncologie, Inria Bordeaux Sud-Ouest, Institut de Mathématiques de Bordeaux, Talence, France.

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.

PMID:
31004380
DOI:
10.1002/psp4.12415
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