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

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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 1 2012

Fingerprint

irinotecan
Ependymoma
Brain Neoplasms
Pediatrics
Disease-Free Survival
Vascular Endothelial Growth Factor B
Vascular Endothelial Growth Factor Receptor-2
Epistaxis
Osteonecrosis
Bevacizumab
Vascular Endothelial Growth Factor A
Fatigue
Headache

Keywords

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

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Clinical Neurology

Cite this

Gururangan, S., Fangusaro, J., Young Poussaint, T., Onar-Thomas, A., Gilbertson, R. J., Vajapeyam, S., ... 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

Lack of efficacy of bevacizumab + irinotecan in cases of pediatric recurrent ependymoma-a pediatric brain tumor consortium study. / Gururangan, Sridharan; Fangusaro, Jason; Young Poussaint, Tina; Onar-Thomas, Arzu; Gilbertson, Richard J.; Vajapeyam, Sridhar; Gajjar, Amar; Goldman, Stewart; Friedman, Henry S.; Packer, Roger J.; Boyett, James M.; Kun, Larry E.

In: Neuro-Oncology, Vol. 14, No. 11, 01.11.2012, p. 1404-1412.

Research output: Contribution to journalArticle

Gururangan, S, Fangusaro, J, Young Poussaint, T, Onar-Thomas, A, Gilbertson, RJ, Vajapeyam, S, Gajjar, A, Goldman, S, Friedman, HS, Packer, RJ, Boyett, JM & Kun, LE 2012, 'Lack of efficacy of bevacizumab + irinotecan in cases of pediatric recurrent ependymoma-a pediatric brain tumor consortium study', Neuro-Oncology, vol. 14, no. 11, pp. 1404-1412. https://doi.org/10.1093/neuonc/nos213
Gururangan S, Fangusaro J, Young Poussaint T, Onar-Thomas A, Gilbertson RJ, Vajapeyam S et al. Lack of efficacy of bevacizumab + irinotecan in cases of pediatric recurrent ependymoma-a pediatric brain tumor consortium study. Neuro-Oncology. 2012 Nov 1;14(11):1404-1412. https://doi.org/10.1093/neuonc/nos213
Gururangan, Sridharan ; Fangusaro, Jason ; Young Poussaint, Tina ; Onar-Thomas, Arzu ; Gilbertson, Richard J. ; Vajapeyam, Sridhar ; Gajjar, Amar ; Goldman, Stewart ; Friedman, Henry S. ; Packer, Roger J. ; Boyett, James M. ; Kun, Larry E. / Lack of efficacy of bevacizumab + irinotecan in cases of pediatric recurrent ependymoma-a pediatric brain tumor consortium study. In: Neuro-Oncology. 2012 ; Vol. 14, No. 11. pp. 1404-1412.
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