Use of bevacizumab as a single agent or in adjunct with traditional chemotherapy regimens in children with unresectable or progressive low-grade glioma

Nataliya Zhukova, Revathi Rajagopal, Adrienne Lam, Lee Coleman, Peter Shipman, Thomas Walwyn, Molly Williams, Michael Sullivan, Martin Campbell, Kanika Bhatia, Nicholas G. Gottardo, Jordan R. Hansford

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25 Citations (Scopus)

Abstract

In pediatric low-grade gliomas not amenable to complete resection, various chemotherapy regimens are the mainstream of treatment. An excellent overall survival of these patients makes justification of the intensification of chemotherapy difficult and calls for the development of new strategies. Bevacizumab, a humanized monoclonal antibody directed against Vascular endothelial growth factor (VEGF), has been successfully used in combination with irinotecan in a number of adult and pediatric studies and reports. Fifteen patients at median age of 7 years old (range 3 months to 15 years) were treated with bevacizumab in combination with conventional low-toxicity chemotherapy. The majority had chiasmatic/hypothalamic and midline tumors, seven had confirmed BRAF pathway alterations including neurofibromatosis type 1 (2). Fourteen patients had more than one progression and three had radiotherapy. No deaths were documented, PFS at 11 and 15 months was 71.5% ± 13.9% and 44.7% ± 17.6% respectively. At the end of follow-up 40% of patients has radiologically stable disease, three patients progressed shortly after completion of bevacizumab and two showed mixed response with progression of cystic component. Rapid visual improvement was seen in 6/8 patients, resolution of endocrine symptoms in 2/4 and motor function improvement in 4/6. No relation between histology or BRAF status and treatment response was observed. Treatment-limiting toxicities included grade 4 proteinuria (2) and hypertension (2) managed with cessation (1) and pausing of therapy plus antihypertensives (1). In conclusion, bevacizumab is well tolerated and appears most effective for rapid tumor control to preserve vision and improve morbidity.

Original languageEnglish
Pages (from-to)40-50
Number of pages11
JournalCancer Medicine
Volume8
Issue number1
DOIs
Publication statusPublished - Jan 2019
Externally publishedYes

Keywords

  • bevacizumab
  • brain tumor
  • cancer
  • humanized monoclonal antibody
  • pediatric low-grade glioma
  • vascular endothelial growth factor

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