title: Efficacy of bevacizumab plus irinotecan in children with recurrent low-grade gliomas--a Pediatric Brain Tumor Consortium study.
abstract: BACKGROUND
  A phase II study of bevacizumab (BVZ) plus irinotecan (CPT-11) was conducted in children with recurrent low-grade glioma to measure sustained response and/or stable disease lasting ≥6 months and progression-free survival.
  
  
  METHODS
  Thirty-five evaluable patients received 2 doses (10 mg/kg each) of single-agent BVZ intravenously 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 neuroimaging and expression of tumor angiogenic markers (vascular endothelial growth factor [VEGF], VEGF receptor 2, hypoxia-inducible factor 2α, and carbonic anhydrase 9).
  
  
  RESULTS
  Thirty-five evaluable patients (median age 8.4 y [range, 0.6-17.6]) received a median of 12 courses of BVZ + CPT-11 (range, 2-26). Twenty-nine of 35 patients (83%) received treatment for at least 6 months. Eight patients progressed on treatment at a median time of 5.4 months (range, 1-17.8). Six patients (17.7%) still in follow-up have had stable disease without receiving additional treatment for a median of 40.1 months (range, 30.6-49.3) from initiating therapy. The 6-month and 2-year progression-free survivals were 85.4% (SE ± 5.96%) and 47.8% (SE ± 9.27%), respectively. The commonest toxicities related to BVZ included grades 1-2 hypertension in 24, grades 1-2 fatigue in 23, grades 1-2 epistaxis in 18, and grades 1-4 proteinuria in 15. The median volume of enhancement decreased significantly between baseline and day 15 (P < .0001) and over the duration of treatment (P < .037).
  
  
  CONCLUSIONS
  The combination of BVZ + CPT-11 appears to produce sustained disease control in some children with recurrent low-grade gliomas.
authors: Corresponding author: Sri Gururangan, MRCP, Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Hanes House, Room 307, 330 Trent Drive, Box 102382, Durham, NC 27710. sridharan.gururangan@dm.duke.edu.
authors: Sridharan
authors: S
authors: Gururangan
authors: Jason
authors: J
authors: Fangusaro
authors: Tina Young
authors: TY
authors: Poussaint
authors: Roger E
authors: RE
authors: McLendon
authors: Arzu
authors: A
authors: Onar-Thomas
authors: Shengjie
authors: S
authors: Wu
authors: Roger J
authors: RJ
authors: Packer
authors: Anu
authors: A
authors: Banerjee
authors: Richard J
authors: RJ
authors: Gilbertson
authors: Frederic
authors: F
authors: Fahey
authors: Sridhar
authors: S
authors: Vajapeyam
authors: Regina
authors: R
authors: Jakacki
authors: Amar
authors: A
authors: Gajjar
authors: Stewart
authors: S
authors: Goldman
authors: Ian F
authors: IF
authors: Pollack
authors: Henry S
authors: HS
authors: Friedman
authors: James M
authors: JM
authors: Boyett
authors: Maryam
authors: M
authors: Fouladi
authors: Larry E
authors: LE
authors: Kun
mesh_terms: D000293:Adolescent; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab; D014408:Biomarkers, Tumor / Q000378:metabolism; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D002648:Child; D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D005910:Glioma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D006801:Humans; D007124:Immunoenzyme Techniques; D007223:Infant; D000077146:Irinotecan; D008297:Male; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000473:pathology; D011379:Prognosis; D015996:Survival Rate
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D014408:Biomarkers, Tumor; D000068258:Bevacizumab; D000077146:Irinotecan; D002166:Camptothecin
keywords: CPT-11; bevacizumab; children; gliomas; recurrent