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Cancer Chemotherapy and Pharmacology
Published in: Cancer Chemotherapy and Pharmacology 4/2015

Open Access 01-04-2015 | Original Article

A pharmacokinetic binding model for bevacizumab and VEGF165 in colorectal cancer patients

Authors: Eirini Panoilia, Emilie Schindler, Epaminontas Samantas, Gerasimos Aravantinos, Haralabos P. Kalofonos, Christos Christodoulou, George P. Patrinos, Lena E. Friberg, Gregory Sivolapenko

Published in: Cancer Chemotherapy and Pharmacology | Issue 4/2015

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Abstract

Purpose

To characterize the population pharmacokinetics of bevacizumab, its binding properties to VEGF165 and the effect of demographic data and VEGF-A polymorphisms on the interplay between bevacizumab serum pharmacokinetics and VEGF165 serum concentrations in patients with colorectal cancer stage IV.

Methods

Bevacizumab and VEGF165 data were collected from 19 adult patients with metastatic colorectal cancer enrolled in an observational clinical study. Bevacizumab was administered with one of the following combinations: 5-FU/Leucovorin/Irinotecan, 5-FU/Leucovorin/Oxaliplatin, Capecitabine/Irinotecan at doses ranging from 5 to 10 mg/kg every 2 or 3 weeks. Data analysis was performed using nonlinear mixed-effects modeling implemented in NONMEM 7.3.

Results

A target-mediated drug disposition model adequately described bevacizumab concentration changes over time and its binding characteristics to VEGF165. The estimated clearance of bevacizumab was 0.18 L/day, the free VEGF165 levels at baseline were 212 ng/L, and the elimination rate constant of free VEGF165 was 0.401 day−1. Body weight was allometrically included in all PK parameters.

Conclusion

The final model adequately described the pre- and post-dose concentrations of total bevacizumab and free VEGF165 in patients with colorectal cancer. Model parameters were consistent with those previously reported for patients with solid tumors. Correlations between the binding affinity of bevacizumab and the VEGF-2578C/A and VEGF-634G/C polymorphisms were noticed.
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Metadata
Title
A pharmacokinetic binding model for bevacizumab and VEGF165 in colorectal cancer patients
Authors
Eirini Panoilia
Emilie Schindler
Epaminontas Samantas
Gerasimos Aravantinos
Haralabos P. Kalofonos
Christos Christodoulou
George P. Patrinos
Lena E. Friberg
Gregory Sivolapenko
Publication date
01-04-2015
Publisher
Springer Berlin Heidelberg
Published in
Cancer Chemotherapy and Pharmacology / Issue 4/2015
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI
https://doi.org/10.1007/s00280-015-2701-3

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