title: Bevacizumab and irinotecan in children with recurrent or refractory brain tumors: toxicity and efficacy trends.
abstract: BACKGROUND
  Bevacizumab, a monoclonal antibody targeting the vascular endothelial growth factor, has proven efficacy in some adult tumors; it is now proposed as a new therapeutic strategy for refractory or recurrent brain tumors in some children, either alone or combinated.
  
  
  METHODS
  We retrospectively analyzed 28 children who received bevacizumab on a compassionate basis for refractory or recurrent brain tumors between June 2007 and August 2010 in 7 French centers. Among them, 12 had high-grade gliomas, 7 low-grade gliomas, 4 ependymomas, 2 primitive neurectodermal tumors, 3 neuroglial tumors. The median age at start of bevacizumab was 11.0 years. Bevacizumab was administered at 5-10 mg/kg every 2 weeks, with concomitant chemotherapy for 27 patients.
  
  
  RESULTS
  Bevacizumab was used in combination with irinotecan in 27 patients. Bevacizumab-related toxicity was mild. Toxicities reported were grade I-II hypertension (n = 4), proteinuria (n = 1), lymphopenia (n = 2), wound healing delay (n = 2). Whereas tumor reduction could be observed in 6:7 patients with low-grade gliomas, no efficacy could be documented in patients with high-grade glioma, nor PNET nor ependymoma.
  
  
  CONCLUSIONS
  Bevacizumab-related acute toxicity appears to be low in children, even in combination with irinotecan. Further prospective trials are required to confirm the hypothetical efficacy of bevacizumab and to assess the risk of long-term toxicity especially in the youngest children.
authors.affiliation: Service d'Oncologie Pédiatrique, CHU Nantes, Nantes, France. marie-laure.couec@chu-nantes.fr
authors.forename: Marie-Laure
authors.initials: ML
authors.lastname: Couec
authors.forename: Nicolas
authors.initials: N
authors.lastname: André
authors.forename: Estelle
authors.initials: E
authors.lastname: Thebaud
authors.forename: Odile
authors.initials: O
authors.lastname: Minckes
authors.forename: Xavier
authors.initials: X
authors.lastname: Rialland
authors.forename: Nadège
authors.initials: N
authors.lastname: Corradini
authors.forename: Isabelle
authors.initials: I
authors.lastname: Aerts
authors.forename: Perrine
authors.initials: P
authors.lastname: Marec Bérard
authors.forename: Franck
authors.initials: F
authors.lastname: Bourdeaut
authors.forename: Pierre
authors.initials: P
authors.lastname: Leblond
mesh_terms: D000293:Adolescent; D000328:Adult; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D000068258:Bevacizumab; D001932:Brain Neoplasms / Q000188:drug therapy*; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D000077146:Irinotecan; D008297:Male; D012189:Retrospective Studies
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D000077146:Irinotecan; D002166:Camptothecin