title: Lack of efficacy of bevacizumab + irinotecan in cases of pediatric recurrent ependymoma--a Pediatric Brain Tumor Consortium study.
abstract: A phase II study of bevacizumab (BVZ) plus irinotecan (CPT-11) was conducted in cases of pediatric recurrent ependymoma (EPN) to estimate sustained objective response rate and progression-free survival (PFS). Eligible patients received 2 doses of single-agent BVZ intravenously (10 mg/kg) 2 weeks apart and then BVZ + CPT-11 every 2 weeks until progressive disease, unacceptable toxicity, or a maximum of 2 years of therapy. Correlative studies included diffusion-weighted and T1 dynamic contrast enhanced permeability imaging and tumor immunohistochemistry for vascular endothelial growth factor (VEGF)-A and -B, hypoxia inducible factor-2α, VEGF receptor (R)-2, and carbonic anhydrase (CA)-9. Thirteen evaluable patients received a median of 3 courses (range, 2-12) of BVZ + CPT-11. No sustained response was observed in any patient. Median time to progression in 10 patients was 2.2 months (range, 1.9-6.3). Two patients had stable disease for 10 months and 12 months, respectively. Six-month PFS was 25.7% (SE = 11.1%). Grades I-III toxicities related to BVZ treatment included fatigue in 4 patients, systemic hypertension in 2, epistaxis in 1, headache in 1, and avascular necrosis of bone in 1. Although there was a decrease in the mean diffusion ratio following 2 doses of BVZ, it did not correlate with PFS. BVZ + CPT-11 was well tolerated but had minimal efficacy in cases of recurrent EPN.
authors.affiliation: Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, North Carolina 27710, USA. sridharan.gururangan@duke.edu
authors.forename: Sridharan
authors.initials: S
authors.lastname: Gururangan
authors.forename: Jason
authors.initials: J
authors.lastname: Fangusaro
authors.forename: Tina
authors.initials: T
authors.lastname: Young Poussaint
authors.forename: Arzu
authors.initials: A
authors.lastname: Onar-Thomas
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Gilbertson
authors.forename: Sridhar
authors.initials: S
authors.lastname: Vajapeyam
authors.forename: Amar
authors.initials: A
authors.lastname: Gajjar
authors.forename: Stewart
authors.initials: S
authors.lastname: Goldman
authors.forename: Henry S
authors.initials: HS
authors.lastname: Friedman
authors.forename: Roger J
authors.initials: RJ
authors.lastname: Packer
authors.forename: James M
authors.initials: JM
authors.lastname: Boyett
authors.forename: Larry E
authors.initials: LE
authors.lastname: Kun
authors.forename: Roger
authors.initials: R
authors.lastname: McLendon
mesh_terms: D000293:Adolescent; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D004806:Ependymoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D000077146:Irinotecan; D053208:Kaplan-Meier Estimate; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D016879:Salvage Therapy / Q000379:methods; D055815:Young Adult
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D000077146:Irinotecan; D002166:Camptothecin