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Tumor Treating Field Therapy in Combination with Bevacizumab for the Treatment of Recurrent Glioblastoma
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Bevacizumab dosing strategy in paediatric cancer patients based on population pharmacokinetic analysis with external

Kelong Han1, Thomas Peyret2, Angelica Quartino1

  • 1Clinical Pharmacology, Genentech Inc., South San Francisco, CA, USA.

British Journal of Clinical Pharmacology
|September 9, 2015
PubMed

Insights

Bevacizumab pharmacokinetics in children are similar to adults, with weight-based dosing being effective. Dosing strategies like BSA or tier-based did not offer significant advantages over weight-based dosing for bevacizumab in pediatric patients.

Area of Science:

  • Pharmacology
  • Clinical Pharmacy
  • Pediatric Oncology

Background:

  • Bevacizumab is a monoclonal antibody used in pediatric oncology.
  • Optimizing bevacizumab dosing in children is crucial for efficacy and safety.
  • Understanding pharmacokinetic variability in pediatric populations is essential.

Purpose of the Study:

  • To evaluate the pharmacokinetics of bevacizumab in pediatric patients.
  • To compare various bevacizumab dosing strategies (weight-based, BSA-based, IBW-based, tier-based) in children.
  • To assess the impact of patient factors on bevacizumab exposure.

Main Methods:

  • Analysis of pharmacokinetic data from 232 pediatric patients across five studies.
  • Utilized NONMEM and R for population pharmacokinetic modeling and simulation.
  • Simulated steady-state exposure under different dosing regimens.

Main Results:

  • Bevacizumab clearance and volume of distribution increased with body weight and were higher in males.
  • Children with primary CNS tumors had higher bevacizumab exposure than those with sarcomas.
  • Body weight-adjusted pharmacokinetic parameters were similar across pediatric age groups and comparable to adults.

Conclusions:

  • Body weight-based dosing of bevacizumab in pediatric patients demonstrates pharmacokinetic similarity to adults.
  • Alternative dosing strategies (BSA, IBW, tier-based) showed no significant benefit over weight-based dosing.
  • Findings may inform dosing guidelines for other therapeutic antibodies in pediatric populations.
Abstract

Keywords:
bevacizumabbody surface areacentral nervous system tumourdosing strategyexternal validationpaediatric

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