PT  - JOURNAL ARTICLE
AU  - Benjamin Schneider
AU  - Arnaud Boyer
AU  - Joseph Ciccolini
AU  - Fabrice Barlési
AU  - Kenneth Wang
AU  - Sébastien Benzekry
AU  - Jonathan Paul Mochel
TI  - Optimal Scheduling of Bevacizumab and Pemetrexed/Cisplatin Dosing in Non-Small Cell Lung Cancer
AID  - 10.1101/540849
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 540849
4099  - http://biorxiv.org/content/early/2019/02/05/540849.short
4100  - http://biorxiv.org/content/early/2019/02/05/540849.full
AB  - 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. 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 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 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.