ArticlePediatric blood & cancer2018
Phase 1 trial, pharmacokinetics, and pharmacodynamics of dasatinib combined with crizotinib in children with recurrent or progressive high-grade and diffuse intrinsic pontine glioma.
Article in Pediatric blood & cancer, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 1 of them a synthesis that pooled it.
What it found
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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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
36 citing papers in PubMed, 1 synthesis or guideline pooled it, 47 citations in OpenAlex.
- Glioblastoma multiforme (GBM): An overview of current therapies and mechanisms of resistance.Pharmacological research · 2021Pooled it
- Targeting Kinase Signaling in Glioblastoma: Structural Optimization, Blood-Brain Barrier Dynamics and Combinatorial Translational Strategies.International journal of molecular sciences · 2026Review
- Combinatorial Targeting of Avapritinib-Driven MAP Kinase Activation in High-Grade Glioma.Research square · 2026Article
- Diffuse Midline Gliomas: Clinical, Diagnostic, and Therapeutic Perspectives.Biomedicines · 2026Review
- Comprehensive Characterization of the Immune Microenvironment Based on Nested Resampling Machine Learning Framework Identifies TRAF3 Interacting Protein 3 as a Promising Regulator to Improve the Resistance to Immunotherapy in Glioma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Article
- Pharmacological Phase I Clinical Trials in Pediatric Brain Tumors (1990-2024): A Historical Perspective.Oncology research · 2025Review
- H3K27-Altered Diffuse Midline Glioma of the Brainstem: From Molecular Mechanisms to Targeted Interventions.Cells · 2024Review
- Apatinib combined with temozolomide in diffuse midline glioma: a novel and effective therapy.BMC cancer · 2024Article
- Advances in pediatric gliomas: from molecular characterization to personalized treatments.European journal of pediatrics · 2024Review
- Radiotherapy plus temozolomide with or without anlotinib in H3K27M-mutant diffuse midline glioma: A retrospective cohort study.CNS neuroscience & therapeutics · 2024Article
- Role of c-Src in Carcinogenesis and Drug Resistance.Cancers · 2023Review
- Cyanine Dye Conjugation Enhances Crizotinib Localization to Intracranial Tumors, Attenuating NF-κB-Inducing Kinase Activity and Glioma Progression.Molecular pharmaceutics · 2023Article
- Differences in survival prognosticators between children and adults with H3K27M-mutant diffuse midline glioma.CNS neuroscience & therapeutics · 2023Article
- A neurodevelopmental epigenetic programme mediated by SMARCD3-DAB1-Reelin signalling is hijacked to promote medulloblastoma metastasis.Nature cell biology · 2023Article
- Practical Recommendations for the Manipulation of Kinase Inhibitor Formulations to Age-Appropriate Dosage Forms.Pharmaceutics · 2022Review
- Receptor tyrosine kinase (RTK) targeting in pediatric high-grade glioma and diffuse midline glioma: Pre-clinical models and precision medicine.Frontiers in oncology · 2022Review
- Small Molecule Inhibitors in Adult High-Grade Glioma: From the Past to the Future.Frontiers in oncology · 2022Review
- The hepatocyte growth factor/mesenchymal epithelial transition factor axis in high-risk pediatric solid tumors and the anti-tumor activity of targeted therapeutic agents.Frontiers in pediatrics · 2022Review
- Population pharmacokinetic analysis of crizotinib in children with progressive/recurrent high-grade and diffuse intrinsic pontine gliomas.Cancer chemotherapy and pharmacology · 2021Article
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
backgroundProgressive/recurrent high-grade and diffuse intrinsic pontine gliomas (DIPGs) are fatal. Treatments targeting molecular pathways critical for these cancers are needed.
methodsWe conducted a phase 1 study (rolling-six design) to establish the safety and maximum tolerated dose (MTD) of dasatinib, an oral platelet-derived growth factor receptor A (PDGFRA) inhibitor, and crizotinib, an oral c-Met inhibitor, in such patients. Pharmacokinetics of both agents were performed. Biomarkers of cellular pathway activation in peripheral-blood mononuclear cells (PBMC) were evaluated before and after administration of dasatinib. PDGFRA and MET amplification, and PDGFRA mutations were studied in tumor samples.
resultsTwenty-five patients were enrolled in this study (median age: 11.9 years). Eleven patients had DIPG. Glioblastoma accounted for 40% of cases. Dasatinib at 50 mg/m
conclusionsThis drug combination was poorly tolerated and its activity was minimal. We do not recommend further testing of this combination in children.
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