Lack of efficacy of bevacizumab + irinotecan in cases of pediatric recurrent ependymoma-a pediatric brain tumor consortium study

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

Research output: Contribution to journalArticle

36 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1404-1412
Number of pages9
JournalNeuro-oncology
Volume14
Issue number11
DOIs
StatePublished - Nov 2012

Keywords

  • CPT-11
  • bevacizumab
  • efficacy
  • ependymoma
  • recurrent

ASJC Scopus subject areas

  • Oncology
  • Clinical Neurology
  • Cancer Research

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    Gururangan, S., Fangusaro, J., Young Poussaint, T., Onar-Thomas, A., Gilbertson, R. J., Vajapeyam, S., Gajjar, A., Goldman, S., Friedman, H. S., Packer, R. J., Boyett, J. M., & Kun, L. E. (2012). Lack of efficacy of bevacizumab + irinotecan in cases of pediatric recurrent ependymoma-a pediatric brain tumor consortium study. Neuro-oncology, 14(11), 1404-1412. https://doi.org/10.1093/neuonc/nos213