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

Authors:
Arnaud Boyer
Arnaud Boyer
Aix Marseille University
Marseille | France
Joseph Ciccolini, Pharm.D. Ph.D.
Joseph Ciccolini, Pharm.D. Ph.D.
La Timone University Hospital of Marseille
Dr
Pharmacokinetics, Oncology
Marseille | France
Fabrice Barlesi
Fabrice Barlesi
Aix Marseille University
Marseille | France
Kenneth Wang
Kenneth Wang
Mayo Clinic
United States

CPT Pharmacometrics Syst Pharmacol 2019 Apr 19. Epub 2019 Apr 19.

Iowa State University College of Veterinary Medicine, Ames, Iowa, USA.

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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https://onlinelibrary.wiley.com/doi/abs/10.1002/psp4.12415
Publisher Site
http://dx.doi.org/10.1002/psp4.12415DOI Listing
April 2019
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References

(Supplied by CrossRef)
Pharmacology and mechanism of action of pemetrexed
Adjei A.A. et al.
Clin. Lung Cancer 2004

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