Erschienen in:
16.06.2016 | Original Research Article
Bevacizumab Pharmacokinetics Influence Overall and Progression-Free Survival in Metastatic Colorectal Cancer Patients
verfasst von:
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
Erschienen in:
Clinical Pharmacokinetics
|
Ausgabe 11/2016
Einloggen, um Zugang zu erhalten
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.