Evidence map›Paper›PMID 24637635›Full record

Trial reportClinical cancer research : an official journal of the American Association for Cancer Research2014

Population pharmacokinetics of bevacizumab in children with osteosarcoma: implications for dosing.

David C Turner, Fariba Navid, Najat C Daw, Shenghua Mao, Jianrong Wu, Victor M Santana, Michael Neel, Bhaskar Rao, Jennifer Reikes Willert, David M Loeb and 4 more

Open access · bronzeAbstract readClinical TrialMulticenter Study
In one paragraph

Trial report in Clinical cancer research : an official journal of the American Association for Cancer Research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed, 1 pooled it
2.8field-weighted citation impact, top 8% of its field
1 · What the graph read from it

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.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

26 citing papers in PubMed, 1 synthesis or guideline pooled it, 43 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Trial
  4. Trial
  5. Article
  6. Article
  7. Bevacizumab in Pediatric Neuro-Oncology.Current oncology (Toronto, Ont.) · 2025
    Review
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  9. Review
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  11. Review
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  16. Article
  17. MicroRNA-128 inhibits EMT of human osteosarcoma cells by directly targeting integrin α2.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016
    Article
  18. Article
  19. Article
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors at 5 institutions in 1 country.

David C TurnerAuthors' Affiliations: Departments of Pharmaceutical Sciences, Oncology, Biostatistics, and Surgery; Preclinical Pharmacokinetic Shared Resource, St. Jude Children's Research Hospital; Department of Pediatrics, College of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee; Division of Pediatrics, MD Anderson Cancer Center, Houston, Texas; Department of Pediatrics, Stanford School of Medicine, Palo Alto, California; and Department of Oncology, Division of Pediatric Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland.
Fariba NavidAuthors' Affiliations: Departments of Pharmaceutical Sciences, Oncology, Biostatistics, and Surgery; Preclinical Pharmacokinetic Shared Resource, St. Jude Children's Research Hospital; Department of Pediatrics, College of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee; Division of Pediatrics, MD Anderson Cancer Center, Houston, Texas; Department of Pediatrics, Stanford School of Medicine, Palo Alto, California; and Department of Oncology, Division of Pediatric Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MarylandAuthors' Affiliations: Departments of Pharmaceutical Sciences, Oncology, Biostatistics, and Surgery; Preclinical Pharmacokinetic Shared Resource, St. Jude Children's Research Hospital; Department of Pediatrics, College of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee; Division of Pediatrics, MD Anderson Cancer Center, Houston, Texas; Department of Pediatrics, Stanford School of Medicine, Palo Alto, California; and Department of Oncology, Division of Pediatric Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland.
Najat C DawAuthors' Affiliations: Departments of Pharmaceutical Sciences, Oncology, Biostatistics, and Surgery; Preclinical Pharmacokinetic Shared Resource, St. Jude Children's Research Hospital; Department of Pediatrics, College of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee; Division of Pediatrics, MD Anderson Cancer Center, Houston, Texas; Department of Pediatrics, Stanford School of Medicine, Palo Alto, California; and Department of Oncology, Division of Pediatric Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland.
Shenghua MaoAuthors' Affiliations: Departments of Pharmaceutical Sciences, Oncology, Biostatistics, and Surgery; Preclinical Pharmacokinetic Shared Resource, St. Jude Children's Research Hospital; Department of Pediatrics, College of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee; Division of Pediatrics, MD Anderson Cancer Center, Houston, Texas; Department of Pediatrics, Stanford School of Medicine, Palo Alto, California; and Department of Oncology, Division of Pediatric Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland.
Jianrong WuAuthors' Affiliations: Departments of Pharmaceutical Sciences, Oncology, Biostatistics, and Surgery; Preclinical Pharmacokinetic Shared Resource, St. Jude Children's Research Hospital; Department of Pediatrics, College of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee; Division of Pediatrics, MD Anderson Cancer Center, Houston, Texas; Department of Pediatrics, Stanford School of Medicine, Palo Alto, California; and Department of Oncology, Division of Pediatric Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland.
Victor M SantanaAuthors' Affiliations: Departments of Pharmaceutical Sciences, Oncology, Biostatistics, and Surgery; Preclinical Pharmacokinetic Shared Resource, St. Jude Children's Research Hospital; Department of Pediatrics, College of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee; Division of Pediatrics, MD Anderson Cancer Center, Houston, Texas; Department of Pediatrics, Stanford School of Medicine, Palo Alto, California; and Department of Oncology, Division of Pediatric Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MarylandAuthors' Affiliations: Departments of Pharmaceutical Sciences, Oncology, Biostatistics, and Surgery; Preclinical Pharmacokinetic Shared Resource, St. Jude Children's Research Hospital; Department of Pediatrics, College of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee; Division of Pediatrics, MD Anderson Cancer Center, Houston, Texas; Department of Pediatrics, Stanford School of Medicine, Palo Alto, California; and Department of Oncology, Division of Pediatric Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland.
Michael NeelAuthors' Affiliations: Departments of Pharmaceutical Sciences, Oncology, Biostatistics, and Surgery; Preclinical Pharmacokinetic Shared Resource, St. Jude Children's Research Hospital; Department of Pediatrics, College of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee; Division of Pediatrics, MD Anderson Cancer Center, Houston, Texas; Department of Pediatrics, Stanford School of Medicine, Palo Alto, California; and Department of Oncology, Division of Pediatric Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland.
Bhaskar RaoAuthors' Affiliations: Departments of Pharmaceutical Sciences, Oncology, Biostatistics, and Surgery; Preclinical Pharmacokinetic Shared Resource, St. Jude Children's Research Hospital; Department of Pediatrics, College of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee; Division of Pediatrics, MD Anderson Cancer Center, Houston, Texas; Department of Pediatrics, Stanford School of Medicine, Palo Alto, California; and Department of Oncology, Division of Pediatric Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland.
Jennifer Reikes WillertAuthors' Affiliations: Departments of Pharmaceutical Sciences, Oncology, Biostatistics, and Surgery; Preclinical Pharmacokinetic Shared Resource, St. Jude Children's Research Hospital; Department of Pediatrics, College of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee; Division of Pediatrics, MD Anderson Cancer Center, Houston, Texas; Department of Pediatrics, Stanford School of Medicine, Palo Alto, California; and Department of Oncology, Division of Pediatric Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland.
David M LoebAuthors' Affiliations: Departments of Pharmaceutical Sciences, Oncology, Biostatistics, and Surgery; Preclinical Pharmacokinetic Shared Resource, St. Jude Children's Research Hospital; Department of Pediatrics, College of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee; Division of Pediatrics, MD Anderson Cancer Center, Houston, Texas; Department of Pediatrics, Stanford School of Medicine, Palo Alto, California; and Department of Oncology, Division of Pediatric Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland.
K Elaine HarsteadAuthors' Affiliations: Departments of Pharmaceutical Sciences, Oncology, Biostatistics, and Surgery; Preclinical Pharmacokinetic Shared Resource, St. Jude Children's Research Hospital; Department of Pediatrics, College of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee; Division of Pediatrics, MD Anderson Cancer Center, Houston, Texas; Department of Pediatrics, Stanford School of Medicine, Palo Alto, California; and Department of Oncology, Division of Pediatric Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland.
Stacy L ThromAuthors' Affiliations: Departments of Pharmaceutical Sciences, Oncology, Biostatistics, and Surgery; Preclinical Pharmacokinetic Shared Resource, St. Jude Children's Research Hospital; Department of Pediatrics, College of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee; Division of Pediatrics, MD Anderson Cancer Center, Houston, Texas; Department of Pediatrics, Stanford School of Medicine, Palo Alto, California; and Department of Oncology, Division of Pediatric Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland.
Burgess B FreemanAuthors' Affiliations: Departments of Pharmaceutical Sciences, Oncology, Biostatistics, and Surgery; Preclinical Pharmacokinetic Shared Resource, St. Jude Children's Research Hospital; Department of Pediatrics, College of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee; Division of Pediatrics, MD Anderson Cancer Center, Houston, Texas; Department of Pediatrics, Stanford School of Medicine, Palo Alto, California; and Department of Oncology, Division of Pediatric Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland.
Clinton F StewartAuthors' Affiliations: Departments of Pharmaceutical Sciences, Oncology, Biostatistics, and Surgery; Preclinical Pharmacokinetic Shared Resource, St. Jude Children's Research Hospital; Department of Pediatrics, College of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee; Division of Pediatrics, MD Anderson Cancer Center, Houston, Texas; Department of Pediatrics, Stanford School of Medicine, Palo Alto, California; and Department of Oncology, Division of Pediatric Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, Maryland clinton.stewart@stjude.org.
The University of Texas MD Anderson Cancer Center · USUniversity of Tennessee Health Science Center · USStanford Medicine · USJohns Hopkins University · USSt. Jude Children's Research Hospital · US

Funding

Viral Vector Technology (VVTSR)P30CA021765 · NCI · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI CHARLES ROBERTS · 1985 to 2026
$166.9M
NCI NIH HHS P30 CA021765NCI NIH HHS P30 CA 21765
6 · The paper itself

Abstract

purposeTo describe sources of interindividual variability in bevacizumab disposition in pediatric patients and explore associations among bevacizumab pharmacokinetics and clinical wound healing outcomes. EXPERIMENTAL

designBefore tumor resection, three doses of bevacizumab (15 mg/kg) were administered to patients (median age, 12.2 years) enrolled in a multi-institutional osteosarcoma trial. Serial sampling for bevacizumab pharmacokinetics was obtained from 27 patients. A population pharmacokinetic model was fit to the data, and patient demographics and clinical chemistry values were systematically tested as predictive covariates on model parameters. Associations between bevacizumab exposure and wound healing status were evaluated by logistic regression.

resultsBevacizumab concentration-time data were adequately described by a two-compartment model. Pharmacokinetic parameter estimates were similar to those previously reported in adults, with a long median (range) terminal half-life of 12.2 days (8.6 to 32.4 days) and a volume of distribution indicating confinement primarily to the vascular space, 49.1 mL/kg (27.1 to 68.3 mL/kg). Body composition was a key determinant of bevacizumab exposure, as body mass index percentile was significantly (P < 0.05) correlated to body-weight normalized clearance and volume of distribution. Furthermore, bevacizumab exposure before primary tumor resection was associated with increased risk of major wound healing complications after surgery (P < 0.05).

conclusionA population pharmacokinetic model for bevacizumab was developed, which demonstrated that variability in bevacizumab exposure using weight-based dosing is related to body composition. Bevacizumab dosage scaling using ideal body weight would provide an improved dosing approach in children by minimizing pharmacokinetic variability and reducing likelihood of major wound healing complications.

Indexed as

Models, BiologicalAdolescentAlgorithmsAngiogenesis InhibitorsAntibodies, Monoclonal, HumanizedArea Under CurveBevacizumabBody Mass IndexBody WeightBone NeoplasmsChildComputer SimulationDose-Response Relationship, DrugFemaleHumansLogistic ModelsAngiogenesis InhibitorsAntibodies, Monoclonal, HumanizedBevacizumab

Identifiers

PMID24637635
PMCPMC4024352
OpenAlexW2144258138

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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.