Itcc Phase Ii Study Of Imatinib Mesylate In Children With Solid Tumors Expressing Imatinib-Sensitive Tyrosine Kinase Receptors.

9003 Background: Imatinib mesylate inhibits selectively specific activations of the platelet-derived growth factor receptor (PDGFR), c-KIT and BCR/ABL tyrosine kinases and is approved for the treatment of chronic myeloid leukemia and gastro-intestinal stromal tumors (GIST). This study evaluated efficacy of imatinib in solid childhood tumors. Methods: Phase II study of imatinib as single agent in children and adolescents with refractory or relapsing solid tumor expressing at least one of the receptors. Patients were to be treated at 340 mg/m2, a dose escalation allowed to 440 mg/m2 after 2 months in case of insignificant improvement. C-KIT, PDGFRα and β expression was determined on archive tissue sections by immunohistochemistry prior to study entry. Gene mutations, pharmacokinetics, pharmacogenetics, and positron emission tomography imaging were assessed. Results: 36 patients, 21 boys, median age 13.7 years (2.2–22.5 y), 12 with brain tumors, 6 fibromatosis, 8 mesenchymal/bone tumors, and 10 other solid tumors, including 1 GIST and 3 chordoma, were treated at 340 mg/m2 daily during a total of 168 months (median 1.9 month/patient, range 0.5–19). 18/36 expressed c-KIT, 10 PDGFRα, 21 PDGRβ; 12 expressed more than one receptor. Ten patients were escalated to 440 mg/m2 due to lack of efficacy. During the 1st month, 17 patients experienced mild toxicity (grade 1 and 2) related to study treatment: gastro-intestinal (n=22), face edema (n=7), asthenia (n=5), tumor induration (n=2), skin toxicity (n=2), thrombocytopenia (n=1). No partial or complete response was observed; 5 patients (2 fibromatosis, 1 GIST, 1 medulloblastoma, 1 pseudo-inflammatory tumor) experiencing durable stable disease have been under treatment for more than 12 months. Interesting tumor stabilization during 10 and 7 months, respectively, was achieved in a brain stem glioma and a renal carcinoma. Glucose uptake on 18FDG PET scan was reduced in a chordoma, although the child progressed and died due to disease. Pharmacokinetic and genetic data are currently evaluated. Conclusions: Imatinib as single agent was well tolerated, but—as used in our study —failed to show measurable anti-tumor effects according the standard criteria in the pediatric malignancies studied. No significant financial relationships to disclose.