Optimal Scheduling of Bevacizumab and Pemetrexed/Cisplatin Dosing in Non‐Small Cell Lung Cancer
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 attract...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Wiley
2019-08-01
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| Series: | CPT: Pharmacometrics & Systems Pharmacology |
| Online Access: | https://doi.org/10.1002/psp4.12415 |
| Summary: | 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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| ISSN: | 2163-8306 |