title: Long-term efficacy and toxicity of bevacizumab-based therapy in children with recurrent low-grade gliomas.
abstract: BACKGROUND
  Because definitive resection or radiotherapy for pediatric low-grade gliomas (LGGs) may be associated with severe and permanent adverse effects, medical management has taken a significant role. Bevacizumab-based therapy has demonstrated encouraging responses; however, longer-term toxicity, response durability and alternative dosing regimens have not been evaluated.
  
  
  METHODS
  This was a retrospective review of children with multiply recurrent, progressive LGGs treated with bevacizumab-based therapy and followed for at least 12 months after treatment completion. Toxicity was uniformly graded and imaging was centrally reviewed.
  
  
  RESULTS
  All fourteen patients had failed at least two prior treatment regimens; six had dissemination. Patients received initial bevacizumab-based therapy at a median age of 5.3 years (range, 1-12 years). Median treatment duration was 12 months (range, 1-24 months). 12 patients had an objective response; 2 had stable disease. Median time to maximum response was 9 weeks (range, 7-17 weeks). No patients progressed on therapy, although 13/14 progressed after stopping bevacizumab at a median of 5 months. Four patients were re-treated with bevacizumab and all again responded or stabilized. Alternative dosing strategies were effective, including bevacizumab monotherapy and prolonging the dosing interval to 3 weeks. High-grade bevacizumab-related toxicities consisted of grade 3 proteinuria (n = 2), primary inflammatory arthritis (n = 1), and somnolence (n = 1). Toxicities resolved within 6 months of treatment cessation except one case of hypertension.
  
  
  CONCLUSIONS
  Bevacizumab-based therapy is successful at inducing rapid LGG response. Patients progressing off-therapy may be successfully re-treated with bevacizumab. Nearly all tumors progress once treatment is discontinued. Toxicities are not insignificant but usually reversible.
authors.affiliation: Division of Oncology, Center for Cancer and Blood Disorders, Children's National Medical Center, Washington, District of Columbia, USA. ehwang@childrensnational.org
authors.forename: Eugene I
authors.initials: EI
authors.lastname: Hwang
authors.forename: Regina I
authors.initials: RI
authors.lastname: Jakacki
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Fisher
authors.forename: Lindsay B
authors.initials: LB
authors.lastname: Kilburn
authors.forename: Marianna
authors.initials: M
authors.lastname: Horn
authors.forename: Gilbert
authors.initials: G
authors.lastname: Vezina
authors.forename: Brian R
authors.initials: BR
authors.lastname: Rood
authors.forename: Roger J
authors.initials: RJ
authors.lastname: Packer
mesh_terms: D020533:Angiogenesis Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects* / Q000627:therapeutic use*; D000068258:Bevacizumab; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy; D002648:Child; D002675:Child, Preschool; D005260:Female; D005910:Glioma / Q000188:drug therapy* / Q000532:radiotherapy; D006801:Humans; D007223:Infant; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab