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.
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.
Authors: Steven G DuBois; Suzanne Shusterman; Joel M Reid; Ashish M Ingle; Charlotte H Ahern; Sylvain Baruchel; Julia Glade-Bender; Percy Ivy; Peter C Adamson; Susan M Blaney Journal: Cancer Chemother Pharmacol Date: 2011-12-18 Impact factor: 3.333
Authors: AeRang Kim; Eva Dombi; Kathleen Tepas; Elizabeth Fox; Staci Martin; Pamela Wolters; Frank M Balis; Nalini Jayaprakash; Baris Turkbey; Naira Muradyan; Peter L Choyke; Alyssa Reddy; Bruce Korf; Brigitte C Widemann Journal: Pediatr Blood Cancer Date: 2012-09-07 Impact factor: 3.167
Authors: Brigitte C Widemann; Aerang Kim; Elizabeth Fox; Sylvain Baruchel; Peter C Adamson; Ashish M Ingle; Julia Glade Bender; Michael Burke; Brenda Weigel; Diana Stempak; Frank M Balis; Susan M Blaney Journal: Clin Cancer Res Date: 2012-09-07 Impact factor: 12.531
Authors: Julia Glade Bender; Susan M Blaney; Scott Borinstein; Joel M Reid; Sylvain Baruchel; Charlotte Ahern; Ashish M Ingle; Darrell J Yamashiro; Alice Chen; Brenda Weigel; Peter C Adamson; Julie R Park Journal: Clin Cancer Res Date: 2012-07-12 Impact factor: 12.531
Authors: Lucas Moreno; Andrew D J Pearson; Xavier Paoletti; Irene Jimenez; Birgit Geoerger; Pamela R Kearns; C Michel Zwaan; Francois Doz; Andre Baruchel; Josef Vormoor; Michela Casanova; Stefan M Pfister; Bruce Morland; Gilles Vassal Journal: Nat Rev Clin Oncol Date: 2017-05-16 Impact factor: 66.675
Authors: Nichole Shaw; Christopher Erickson; Stephanie J Bryant; Virginia L Ferguson; Melissa D Krebs; Nancy Hadley-Miller; Karin A Payne Journal: Tissue Eng Part B Rev Date: 2017-09-28 Impact factor: 6.389
Authors: Theodore W Laetsch; Steven G DuBois; Julia Glade Bender; Margaret E Macy; Lucas Moreno Journal: Cancer Discov Date: 2020-12-04 Impact factor: 38.272
Authors: Marie-Therese Haider; Keith D Hunter; Simon P Robinson; Timothy J Graham; Eva Corey; T Neil Dear; Russell Hughes; Nicola J Brown; Ingunn Holen Journal: Bone Date: 2015-08-14 Impact factor: 4.398