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Clinical Pharmacokinetics
Published in: Clinical Pharmacokinetics 11/2016

01-11-2016 | Original Research Article

Bevacizumab Pharmacokinetics Influence Overall and Progression-Free Survival in Metastatic Colorectal Cancer Patients

Authors: Morgane Caulet, Thierry Lecomte, Olivier Bouché, Jérôme Rollin, Valérie Gouilleux-Gruart, Nicolas Azzopardi, Julie Léger, Christophe Borg, Jean-Yves Douillard, Sylvain Manfredi, Denis Smith, Olivier Capitain, Aurélie Ferru, Driffa Moussata, Eric Terrebone, Gilles Paintaud, David Ternant

Published in: Clinical Pharmacokinetics | Issue 11/2016

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Abstract

Objective

Clinical response to bevacizumab varies between patients treated for metastatic colorectal cancer (mCRC). The aim of this study was to quantify individual factors affecting bevacizumab pharmacokinetic variability and assess the relationship between bevacizumab concentrations and clinical outcomes.

Methods

Bevacizumab pharmacokinetics were assessed in 130 mCRC patients using a two-compartment pharmacokinetic population model. Overall and progression-free survival (PFS) were analyzed using Cox models.

Results

The bevacizumab volume of distribution increased with height (p = 10−10) and was higher in patients with a 3/3 variable number tandem repeat of the FCGRT (Fc fragment of IgG receptor and transporter) gene (p = 0.039). The elimination rate constant increased with baseline carcinoembryonic antigen (CEA) and vascular endothelial growth factor (VEGF) concentrations, and was higher in patients with extra-hepatic metastases (p = 0.00029, 0.011, and 0.014). A bevacizumab trough concentration ≤15.5 mg/L was associated with both shorter overall survival and PFS (hazard ratio [95 % CI] 1.90 [1.20–2.99] and 1.76 [1.20–2.58], respectively).

Conclusion

High tumour burden is associated with low bevacizumab concentrations, and high bevacizumab concentration are associated with both decreased overall and progression-free survivals.
Appendix
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Metadata
Title
Bevacizumab Pharmacokinetics Influence Overall and Progression-Free Survival in Metastatic Colorectal Cancer Patients
Authors
Morgane Caulet
Thierry Lecomte
Olivier Bouché
Jérôme Rollin
Valérie Gouilleux-Gruart
Nicolas Azzopardi
Julie Léger
Christophe Borg
Jean-Yves Douillard
Sylvain Manfredi
Denis Smith
Olivier Capitain
Aurélie Ferru
Driffa Moussata
Eric Terrebone
Gilles Paintaud
David Ternant
Publication date
01-11-2016
Publisher
Springer International Publishing
Published in
Clinical Pharmacokinetics / Issue 11/2016
Print ISSN: 0312-5963
Electronic ISSN: 1179-1926
DOI
https://doi.org/10.1007/s40262-016-0406-3

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