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Author Notes:

Correspondence: Cynthia Wetmore, Aflac Cancer and Blood Disorders Center, Children’s Healthcare of Atlanta, Department of Pediatrics, Emory University School of Medicine, 1760 Haygood Drive, Atlanta 30322, GA. Tel: 404-778-5692; Fax: 404-727-4455; Email: cynthia.wetmore@emory.edu

Conflict of Interest: None declared.


Research Funding:

This research was Supported, in part, by the US National Institutes of Health Cancer Center Support CORE Grant P30 CA21765, the National Childhood Cancer Foundation (NCCF) Grant 5 U10 CA98543-10, the America Lebanese Syrian Associated Charities (ALSAC), and the Carter Samuel Martin Developmental Therapeutics Endowment


  • Science & Technology
  • Life Sciences & Biomedicine
  • Oncology
  • Ependymoma
  • Pediatric
  • recurrent brain tumor
  • tyrosine kinase inhibitor
  • MALATE SU11248

Phase II evaluation of sunitinib in the treatment of recurrent or refractory high-grade glioma or ependymoma in children: a children's Oncology Group Study ACNS1021

Journal Title:

Cancer Medicine


Volume 5, Number 7


, Pages 1416-1424

Type of Work:

Article | Final Publisher PDF


Sunitinib malate is a small multi-targeted tyrosine kinase inhibitor that inhibits vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor (PDGFR) and stem cell factor receptor (KIT), which are highly expressed by some high-grade brain tumors. We conducted a phase II study to estimate the efficacy and further characterize the pharmacokinetics of sunitinib in pediatric patients with recurrent or refractory high-grade glioma (Stratum A) or ependymoma (Stratum B). This was a prospective, multicenter Phase II trial conducted through the Children's Oncology Group (ClinicalTrials.gov Identifier NCT01462695). Sunitinib, 15 mg/m2, was orally administered once daily for 4 weeks every 6 weeks. The safety and tolerability of sunitinib, an estimate of progression-free survival (PFS), analyses of sunitinib pharmacokinetics (PK) and pharmacodynamics modulation of plasma VEGF and VEGFR2 were also assessed. Thirty eligible patients (17 patients on Stratum A, 13 patients on Stratum B) were enrolled and 29 patients were evaluable for response. Sunitinib was reasonably well tolerated in children with recurrent ependymoma or high-grade glioma. Most adverse events were of mild-to-moderate severity and manageable with supportive treatment. While there was a statistically significant modulation of plasma VEGFR2 with sunitinib exposure, there were no sustained tumor responses. Both strata were closed at time of planned interim analysis as there was not sufficient efficacy associated with sunitinib in children with recurrent brain tumors. Sunitinib was well tolerated in children and young adults with recurrent high-grade glioma or ependymoma but had no single agent objective antitumor activity in these patients.

Copyright information:

© 2016 The Authors.

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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