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

Schneider, B.; Boyer, A.; Ciccolini, J.; Barlesi, F.; Wang, K.; Benzekry, S.; Mochel, J. P.

doi:10.1101/540849

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bioRxiv · 10.1101/540849

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

Schneider, B.·Boyer, A.·Ciccolini, J.·Barlesi, F.·Wang, K.·Benzekry, S.·Mochel, J. P.

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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. 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.

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Schneider, B., Boyer, A., Ciccolini, J., Barlesi, F., Wang, K., Benzekry, S., Mochel, J. P.. 2019-02-05. Optimal Scheduling of Bevacizumab and Pemetrexed/Cisplatin Dosing in Non-Small Cell Lung Cancer. https://doi.org/10.1101/540849

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