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  • Title: Target-driven exploratory study of imatinib mesylate in children with solid malignancies by the Innovative Therapies for Children with Cancer (ITCC) European Consortium.
    Author: Geoerger B, Morland B, Ndiaye A, Doz F, Kalifa G, Geoffray A, Pichon F, Frappaz D, Chatelut E, Opolon P, Hain S, Boderet F, Bosq J, Emile JF, Le Deley MC, Capdeville R, Vassal G, Innovative Therapies for Children with Cancer European Consortium.
    Journal: Eur J Cancer; 2009 Sep; 45(13):2342-51. PubMed ID: 19362466.
    Abstract:
    AIM: To explore imatinib efficacy and pharmacokinetics in children and adolescents with refractory/relapsing solid tumours, expressing imatinib-sensitive receptor tyrosine kinases. METHODS: Exploratory study on imatinib in tumours expressing, at least, one of the receptors KIT or platelet-derived growth factor receptor (PDGFR). Standard radiological response evaluation, pharmacokinetics, gene mutations and positron emission tomography imaging were assessed. RESULTS: Thirty-six patients (median age: 13.7 years) with brain (12), mesenchymal/bone (14) or other solid tumours, received imatinib 340 mg/m(2)/d over a total of 255 months. Fifteen tumours expressed KIT in 30% cells, 19 expressed PDGFRA and 25 expressed PDGFRB. Twenty patients experienced grades 1-2 treatment-related toxicities. Ten patients achieved stable disease; one chordoma had metabolic response. Pharmacokinetic data showed high inter-patient variability (variation coefficient: 44% and 53% for plasma imatinib and CGP 74588 AUCs, respectively). CONCLUSIONS: Imatinib was tolerated well, but failed to show efficacy according to standard criteria in paediatric malignancies expressing KIT or PDGFR.
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