piperidines and Osteonecrosis

To evaluate the growing skeleton for potential altered skeletalgenesis associated with antiangiogenesis therapy.. Knee radiographs and magnetic resonance imaging (MRI) were prospectively obtained on patients enrolled on two consecutive clinical trials using vandetanib, a potent oral (VEGF receptor 2) VEGFR-2 inhibitor alone or combined with dasatinib, a multiple tyrosine kinase inhibitor, in children with newly diagnosed diffuse intrinsic pontine glioma (DIPG).. Fifty-nine patients (32 females) underwent 119 MRIs; 51 patients underwent 89 radiographs of the knees. The median age at enrollment was 6.2 years (range, 2.4-17.6 years). The dose of vandetanib ranged from 50 to 145 mg/m(2) /day. The median treatment duration was 205 days. Only two patients have not experienced disease progression after 18 and 60 months from diagnosis. MRI identified clinically significant premature physeal fusion in both knees of one patient, focal physeal thickening in one, osteonecrosis in eight patients (present at enrollment in one), and bony spicules crossing the physis in two patients (bilateral in one). MRI follow-up period averaged 5.3 months (range, 0-25.5 months; median, 3.5 months). Radiographs delineated normally fused physes in two patients but no cases of premature physeal fusion, osteonecrosis or bony spicules.. As MRI provided greater information than radiographs, and thus would be a more sensitive test to assess skeletalgenesis in pediatric patients.

Topics: Adolescent; Adult; Angiogenesis Inhibitors; Brain Stem Neoplasms; Child; Child, Preschool; Dasatinib; Female; Follow-Up Studies; Glioma; Humans; Infant; Knee Joint; Magnetic Resonance Imaging; Male; Osteonecrosis; Piperidines; Prospective Studies; Protein Kinase Inhibitors; Pyrimidines; Quinazolines; Radiography; Thiazoles; Vascular Endothelial Growth Factor Receptor-2