Target-driven exploratory study of imatinib mesylate in children with solid malignancies by the Innovative Therapies for Children with Cancer (ITCC) European Consortium

被引：46

作者：

Geoerger, Birgit ^{[1
,2
]}

Morland, Bruce ^{[3
]}

Ndiaye, Anna ^{[2
]}

Doz, Francois ^{[4
]}

Kalifa, Gabriel ^{[5
]}

Geoffray, Anne ^{[6
]}

Pichon, Fabienne ^{[7
]}

Frappaz, Didier ^{[8
]}

Chatelut, Etienne ^{[9
]}

Opolon, Paule ^{[10
]}

Hain, Sharon ^{[11
]}

Boderet, Francoise ^{[12
]}

Bosq, Jacques ^{[13
]}

Emile, Jean-Francois ^{[14
]}

Le Deley, Marie-Cecile ^{[2
]}

Capdeville, Renaud ^{[15
]}

Vassal, Gilles ^{[1
,2
]}

机构：

[1] Inst Gustave Roussy, Dept Paediat, F-94805 Villejuif, France

[2] Univ Paris 11, Paris, France

[3] Childrens Hosp, Birmingham B4 6NH, W Midlands, England

[4] Inst Curie, F-75248 Paris 05, France

[5] CHU Cochin Port Royal, F-75014 Paris, France

[6] CHU Fdn Lenval, F-06000 Nice, France

[7] Ctr Oscar Lambret, F-59020 Lille, France

[8] Ctr Leon Berard, F-69373 Lyon, France

[9] Inst Claudius Regaud, EA3035, F-31052 Toulouse, France

[10] Inst Gustave Roussy, Vectorol & Gene Transfer UMR8121, F-94805 Villejuif, France

[11] Univ Coll Hosp, London NW1 2BU, England

[12] CHU Nantes, F-44093 Nantes, France

[13] Inst Gustave Roussy, Dept Pathol, F-94805 Villejuif, France

[14] Ctr Ambroise Pare, Dept Pathol, F-92104 Boulogne, France

[15] Novartis Pharma AG, CH-4002 Basel, Switzerland

来源：

EUROPEAN JOURNAL OF CANCER | 2009年 / 45卷 / 13期

关键词：

Tyrosine kinase inhibitors; Childhood solid tumours; Exploratory study; BRAIN-TUMOR CONSORTIUM; GROWTH-FACTOR-B; PHASE-I TRIAL; C-KIT; EXPRESSION; RECEPTOR; LEUKEMIA; GLIOMAS; PHARMACOKINETICS; MUTATIONS;

D O I：

10.1016/j.ejca.2009.03.007

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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. (C) 2009 Elsevier Ltd. All rights reserved.

引用

页码：2342 / 2351

页数：10

共 37 条

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