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: Sridharan Gururangan, Jason Fangusaro, Tina Young Poussaint, Arzu Onar-Thomas, Richard J Gilbertson, Sridhar Vajapeyam, Amar Gajjar, Stewart Goldman, Henry S Friedman, Roger J Packer, James M Boyett, Larry E Kun, Roger McLendon
• Journal: Neuro-oncology (Neuro Oncol) Vol. 14 Issue 11 Pg. 1404-12 (Nov 2012) ISSN: 1523-5866 [Electronic] England
• PMID: 23019233 (Publication Type: Clinical Trial, Phase II, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal, Humanized
• Bevacizumab
• Irinotecan
• Camptothecin

Topics

• Adolescent
• Antibodies, Monoclonal, Humanized (administration & dosage, adverse effects)
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Bevacizumab
• Brain Neoplasms (drug therapy, mortality, pathology)
• Camptothecin (administration & dosage, adverse effects, analogs & derivatives)
• Child
• Child, Preschool
• Disease-Free Survival
• Ependymoma (drug therapy, mortality, pathology)
• Female
• Humans
• Immunohistochemistry
• Irinotecan
• Kaplan-Meier Estimate
• Male
• Neoplasm Recurrence, Local (drug therapy, mortality, pathology)
• Salvage Therapy (methods)
• Young Adult