ArticleBritish journal of clinical pharmacology2016
Bevacizumab dosing strategy in paediatric cancer patients based on population pharmacokinetic analysis with external validation.
Article in British journal of clinical pharmacology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. It is linked to trial NCT00381797 (Phase II Study of Bevacizumab Plus Irinotecan), which is not on this map. Cited by 25 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Phase II Study of Bevacizumab Plus Irinotecan (Camptosar™) in Children With Recurrent, Progressive, or Refractory Malignant Gliomas, Diffuse/Intrinsic Brain Stem Gliomas, Medulloblastomas, Ependymomas and Low Grade Gliomas
Who cites it
25 citing papers in PubMed, 42 citations in OpenAlex.
- Combination of bevacizumab, irinotecan, and temozolomide for refractory or relapsed neuroblastoma: Results of a phase II study.Pediatric blood & cancer · 2017Trial
- Utilizing Minimal Physiologically Based Pharmacokinetic Modeling to Bridge Bevacizumab Pharmacokinetics from Adult to Pediatric Patients.The AAPS journal · 2025Article
- Prediction of Monoclonal Antibody Pharmacokinetics in Pediatric Populations Using PBPK Modeling and Simulation.Pharmaceutics · 2025Article
- Pharmacological Phase I Clinical Trials in Pediatric Brain Tumors (1990-2024): A Historical Perspective.Oncology research · 2025Review
- Distribution of Bevacizumab into the Cerebrospinal Fluid of Children and Adolescents with Recurrent Brain Tumors.Paediatric drugs · 2024Article
- Nivolumab and ipilimumab population pharmacokinetics in support of pediatric dose recommendations-Going beyond the body-size effect.CPT: pharmacometrics & systems pharmacology · 2024Article
- Application of Modelling and Simulation Approaches to Predict Pharmacokinetics of Therapeutic Monoclonal Antibodies in Pediatric Population.Pharmaceutics · 2023Review
- Targeting Angiogenic Factors for the Treatment of Medulloblastoma.Current treatment options in oncology · 2022Review
- Review
- Review
- Antiangiogenic Compound Axitinib Demonstrates Low Toxicity and Antitumoral Effects against Medulloblastoma.Cancers · 2021Article
- Pharmacokinetic Variability of Therapeutic Antibodies in Humans: A Comprehensive Review of Population Pharmacokinetic Modeling Publications.Clinical pharmacokinetics · 2020Review
- The Actions of IGF-1 in the Growth Plate and Its Role in Postnatal Bone Elongation.Current osteoporosis reports · 2020Review
- Physiologically Based Pharmacokinetic Modeling of Monoclonal Antibodies in Pediatric Populations Using PK-Sim.Frontiers in pharmacology · 2020Article
- Correction.British journal of clinical pharmacology · 2019Article
- Monoclonal Antibodies and Fc-Fusion Proteins for Pediatric Use: Dosing, Immunogenicity, and Modeling and Simulation in Data Submitted to the US Food and Drug Administration.Journal of clinical pharmacology · 2019Article
- A Retrospective Evaluation of Allometry, Population Pharmacokinetics, and Physiologically-Based Pharmacokinetics for Pediatric Dosing Using Clearance as a Surrogate.CPT: pharmacometrics & systems pharmacology · 2019Article
- Influence of Antigen Mass on the Pharmacokinetics of Therapeutic Antibodies in Humans.Clinical pharmacokinetics · 2019Review
- Population pharmacokinetics and individualized lobaplatin regimen for the treatment of Chinese small cell lung cancer in the elderly.Medicine · 2019Article
- Article
Corrections and comments
- Erratum issuedCorrection.2019
Authors and funding
13 authors at 8 institutions in 4 countries.
Funding
Abstract
aimThe aim of the present study was to evaluate the pharmacokinetics of bevacizumab and various dosing strategies for this agent in paediatric patients.
methodsData were collected from 232 paediatric patients (1971 concentrations) in five studies, with a wide range of age (0.5-21 years), body weight (BWT; 5.9-125 kg), and regimens (5-15 mg kg(-1) biweekly or triweekly). Data from 152 patients (1427 concentrations) and 80 patients (544 concentrations) were used for model building and external validation, respectively. Steady-state exposure was simulated under BWT-based, body surface area (BSA)-based, ideal body weight (IBW)-based, and tier-based doses. NONMEM and R were used for analyses.
resultsTypical estimates of clearance, central volume of distribution (V1), and median half-life were 9.04 ml h(-1) , 2851 ml, and 19.6 days, respectively. Clearance decreased with increasing albumin. Clearance and V1 increased with BWT and were higher in male patients. Clearance and V1 were lower in children with primary central nervous system (CNS) tumours than in children with sarcomas, resulting in 49% higher trough (C min) and 29% higher peak (Cmax) concentrations. BWT-adjusted clearance and V1 remained unchanged across ages. Paediatric C min was similar to adult C min under all dosing strategies. Paediatric Cmax exceeded adult Cmax under tier-based doses.
conclusionsBWT-adjusted pharmacokinetic parameter estimates in paediatric patients were similar to those in adults, and similar across ages. Bevacizumab exposure was higher in children with primary CNS tumours than in children with sarcomas. BSA-based, IBW-based, and tier-based doses offered no substantial advantage over the BWT-based dose currently used in adults for bevacizumab. Given the similarity in pharmacokinetics among many monoclonal antibodies, this may help to develop practical paediatric dosing guidelines for other therapeutic antibodies.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.