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.
- Abbreviations
- adm
- Administer, administered, administration, etc.
- BIC
- Bayesian Information Criteria
- BSA
- Body Surface Area
- CT
- Combination Therapy
- DNA
- Deoxyribonucleic acid
- Gap
- Short for the administration gap between (first) bevacizumab and (second) pemetrexed/cisplatin
- IP
- Intraperitoneal
- IIV
- Inter-individual variability
- IV
- Intravenous
- NSCLC
- Non-Small Cell Lung Carcinoma
- PD
- Pharmacodynamic
- PK/PD
- Pharmacokinetic/pharmacodynamic
- PEM/CIS
- Pemetrexed/cisplatin
- BEV-PEM/CIS
- Pemetrexed/cisplatin-bevacizumab
- PK
- Pharmacokinetics
- ROS
- Reactive Oxygen Species
- RFU
- Relative Fluorescence Units
- sGOF
- Standard Goodness-Of-Fit
- VPC
- Visual Predictive Check
Footnotes
↵* co-last authors.
Conflict of Interest/Disclosure: J.C. received fees for participating to Boards from Roche Laboratory. B.K.S., A.B., F.B., K.W., S.B., and J.P. have no conflicts of interest to declare.
Funding: The work reported in this manuscripted was not funded or sponsered.