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Open Access 08-04-2024 | Bevacizumab | Original Research Article

Distribution of Bevacizumab into the Cerebrospinal Fluid of Children and Adolescents with Recurrent Brain Tumors

Authors: Iris K. Minichmayr, Ursula Knaack, Johannes Gojo, Daniel Senfter, Christine Haberler, Amedeo A. Azizi, Lisa Mayr, Markus Zeitlinger, Andreas Peyrl

Published in: Pediatric Drugs

Abstract

Background

To date, evidence has been lacking regarding bevacizumab pharmacokinetics in the cerebrospinal fluid (CSF).

Objective

This study assessed the penetration of bevacizumab, as part of a metronomic antiangiogenic treatment regimen, into the CSF of children, adolescents, and young adults with recurrent brain tumors.

Patients and Methods

Serum and CSF concentrations, malignant cells, and vascular endothelial growth factor A (VEGF-A) were analyzed in 12 patients (5–27 years) following 10 mg/kg bevacizumab intravenous biweekly administration (EudraCT number 2009-013024-23). A population pharmacokinetic model including body weight, albumin, and tumor type as influential factors was extended to quantify the CSF penetration of bevacizumab.

Results

Apart from in serum (minimum concentration/maximum concentration [C_min/C_max] 77.0–305/267–612 mg/L, median 144/417 mg/L), bevacizumab could be quantified in the CSF (0.01–2.26 mg/L, median 0.35 mg/L). The CSF/serum ratio was 0.16 and highly variable between patients. Malignant cells could be detected in CSF before initiation of treatment in five of 12 patients; after treatment, the CSF was cleared in all patients. VEGF-A was detected in three patients before treatment (mean ± SD: 20 ± 11 pg/mL), and was still measurable in one of these patients despite treatment (16 pg/mL).

Conclusions

This pharmacokinetic pilot study indicated penetration of bevacizumab into the CSF in a population of children, adolescents, and young adults with recurrent brain tumors.

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Title: Distribution of Bevacizumab into the Cerebrospinal Fluid of Children and Adolescents with Recurrent Brain Tumors
Authors: Iris K. Minichmayr
Ursula Knaack
Johannes Gojo
Daniel Senfter
Christine Haberler
Amedeo A. Azizi
Lisa Mayr
Markus Zeitlinger
Andreas Peyrl
Publication date: 08-04-2024
Publisher: Springer International Publishing
Keywords: Bevacizumab
Brain Tumor
Pharmacokinetics
Published in: Pediatric Drugs
Print ISSN: 1174-5878
Electronic ISSN: 1179-2019
DOI: https://doi.org/10.1007/s40272-024-00624-y

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Distribution of Bevacizumab into the Cerebrospinal Fluid of Children and Adolescents with Recurrent Brain Tumors

Abstract

Background

Objective

Patients and Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Objective

Patients and Methods

Results

Conclusions

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