Citations 1
Optimal Scheduling of Bevacizumab and Pemetrexed/Cisplatin Dosing in Non‐Small Cell Lung Cancer
Schneider, Benjamin , Boyer, Arnaud, Ciccolini, Joseph , Benzekry, Sébastien , Mochel, Jonathan P. , Mochel, Jonathan P , Barlési, Fabrice , Wang, Kenneth
CPT: Pharmacometrics & Systems Pharmacology | April 20, 2019 | Volume: 8 | Issue: 8 | Pages: 577-586
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.