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Growth plate abnormalities in pediatric cancer patients undergoing phase 1 anti‐angiogenic therapy: A report from the children's oncology group phase I consortium

Year: 2014
Type: article
Abstract: BACKGROUND: Pre-clinical studies suggest that anti-angiogenic agents may be toxic to the developing growth plate. The purpose of this study was to evaluate the incidence of growth plate abnormalities in children with refractory cancer undergoing anti-angiogenic therapy. PROCEDURE: Targeted radiographic studies from 53 subjects enrolled on six separate Children's Oncology Group Phase 1 and Pilot Consortium clinical trials evaluating new anti-cancer agents interfering with angiogenesis were reviewed. Subjects received tyrosine kinase inhibitors with anti-angiogenic effects (n = 35), monoclonal antibodies targeting vascular endothelial growth factor (VEGF) (n = 13), or angiopoietin (n = 5). Radiographs of their distal femur/proximal tibia were obtained at baseline. Follow-up radiographs were obtained after odd-numbered treatment cycles in patients with open growth plates who did not experience disease progression prior to cycle 3. RESULTS: Baseline and follow-up growth plate radiographs were acquired in 48/53 (90%) of patients. Five patients (9.4%), all of whom received a specific VEGF/VEGFR blocking agent (sunitinib [n = 1] or pazopanib [n = 4]), had growth plate abnormalities. Four patients had growth plate widening that was apparent on at least two successive radiographs, but was not confirmed by MRI. The fifth patient had progressive growth plate widening and evidence of physeal cartilage hypertrophy on MRI. Subsequent off treatment radiographs showed that the growth plate changes were reversible. CONCLUSION: Growth plate abnormalities occur in a small, but relevant number of patients undergoing anti-angiogenic therapy. These results support the need for growth plate monitoring in children with open growth plates who are receiving anti-angiogenic therapy, and for improved methods to assess toxicity of anti-angiogenic agents to the developing skeleton.
DOI: 10.1002/pbc.25229
Authors: Stephan D. Voss, Julia Glade‐Bender, Sheri L. Spunt, Steven G. DuBois, Brigitte C. Widemann, Julie R. Park, Sarah E. S. Leary, Marvin D. Nelson, Peter C. Adamson, Susan M. Blaney, Brenda Weigel
Institutions: Boston Children's Hospital, Dana-Farber Cancer Institute, Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Columbia University Irving Medical Center, Columbia University, Lucile Packard Children's Hospital, Stanford University, University of California, San Francisco, University of California San Francisco Medical Center, National Institutes of Health, National Cancer Institute, Center for Cancer Research, Seattle Children's Hospital, Children's Hospital Los Angeles, Children's Hospital of Philadelphia, Baylor College of Medicine, University of Minnesota, University of Minnesota Children's Hospital
Language: English
Open Access status: green
OpenAlex ID: W1608409875
FWCI: 1.582
Cites: 35
Cited by: 30
Related to: 10