Optimal Scheduling of Bevacizumab and Pemetrexed/Cisplatin Dosing in Non-Small Cell Lung Cancer.
Animals
Antineoplastic Combined Chemotherapy Protocols
/ administration & dosage
Bevacizumab
/ administration & dosage
Carcinoma, Non-Small-Cell Lung
/ drug therapy
Cell Line, Tumor
Cisplatin
/ administration & dosage
Drug Administration Schedule
Female
Humans
Lung Neoplasms
/ drug therapy
Mice
Models, Biological
Pemetrexed
/ administration & dosage
Treatment Outcome
Xenograft Model Antitumor Assays
Journal
CPT: pharmacometrics & systems pharmacology
ISSN: 2163-8306
Titre abrégé: CPT Pharmacometrics Syst Pharmacol
Pays: United States
ID NLM: 101580011
Informations de publication
Date de publication:
08 2019
08 2019
Historique:
received:
06
02
2019
accepted:
31
03
2019
pubmed:
21
4
2019
medline:
17
6
2020
entrez:
21
4
2019
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 31004380
doi: 10.1002/psp4.12415
pmc: PMC6709425
doi:
Substances chimiques
Pemetrexed
04Q9AIZ7NO
Bevacizumab
2S9ZZM9Q9V
Cisplatin
Q20Q21Q62J
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
577-586Informations de copyright
© 2019 The Authors CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals, Inc. on behalf of the American Society for Clinical Pharmacology and Therapeutics.
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