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Cancer Med. 2016 Jul;5(7):1416-24. doi: 10.1002/cam4.713. Epub 2016 Apr 25.

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.

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Department of Pediatrics, Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta and Emory University School of Medicine, 1760 Haygood Drive NE, Atlanta, Georgia, 30322.
Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, Tennessee, 38105.
Department of Biostatistics, St. Jude Children's Research Hospital, Memphis, Tennessee, 38105.
Department of Hematology/Oncology, Seattle Children's Hospital, Seattle, Washington, 98145.
Pediatric Oncology, Clinical Care Center, Baylor College of Medicine, Houston, Texas, 77030.
Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee, 38105.


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 ( 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.


Ependymoma; Pediatric; recurrent brain tumor; tyrosine kinase inhibitor

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