title: Safety and efficacy of bevacizumab with hypofractionated stereotactic irradiation for recurrent malignant gliomas.
abstract: OBJECTIVE
  Preclinical studies suggest that inhibition of vascular endothelial growth factor (VEGF) improves glioma response to radiotherapy. Bevacizumab, a monoclonal antibody against VEGF, has shown promise in recurrent gliomas, but the safety and efficacy of concurrent bevacizumab with brain irradiation has not been extensively studied. The objectives of this study were to determine the safety and activity of this combination in malignant gliomas.
  
  
  METHODS
  After prior treatment with standard radiation therapy patients with recurrent glioblastoma (GBM) and anaplastic gliomas (AG) received bevacizumab (10 mg/kg intravenous) every 2 weeks of 28-day cycles until tumor progression. Patients also received 30 Gy of hypofractionated stereotactic radiotherapy (HFSRT) in five fractions after the first cycle of bevacizumab.
  
  
  RESULTS
  Twenty-five patients (20 GBM, 5 AG; median age 56 years; median Karnofsky Performance Status 90) received a median of seven cycles of bevacizumab. One patient did not undergo HFSRT because overlap with prior radiotherapy would exceed the safe dose allowed to the optic chiasm. Three patients discontinued treatment because of Grade 3 central nervous system intratumoral hemorrhage, wound dehiscence, and bowel perforation. Other nonhematologic and hematologic toxicities were transient. No radiation necrosis was seen in these previously irradiated patients. For the GBM cohort, overall response rate was 50%, 6-month progression-free survival was 65%; median overall survival was 12.5 months, and 1-year survival was 54%.
  
  
  CONCLUSIONS
  Bevacizumab with HFSRT is safe and well tolerated. Radiographic responses, duration of disease control, and survival suggest that this regimen is active in recurrent malignant glioma.
authors.affiliation: Department of Neurosurgery, The Brain Tumor Center, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA. gutinp@mskcc.org
authors.forename: Philip H
authors.initials: PH
authors.lastname: Gutin
authors.forename: Fabio M
authors.initials: FM
authors.lastname: Iwamoto
authors.forename: Kathryn
authors.initials: K
authors.lastname: Beal
authors.forename: Nimish A
authors.initials: NA
authors.lastname: Mohile
authors.forename: Sasan
authors.initials: S
authors.lastname: Karimi
authors.forename: Bob L
authors.initials: BL
authors.lastname: Hou
authors.forename: Stella
authors.initials: S
authors.lastname: Lymberis
authors.forename: Yoshiya
authors.initials: Y
authors.lastname: Yamada
authors.forename: Jenghwa
authors.initials: J
authors.lastname: Chang
authors.forename: Lauren E
authors.initials: LE
authors.lastname: Abrey
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D001254:Astrocytoma / Q000188:drug therapy / Q000601:surgery; D000068258:Bevacizumab; D001932:Brain Neoplasms / Q000188:drug therapy / Q000601:surgery; D003131:Combined Modality Therapy / Q000009:adverse effects; D018572:Disease-Free Survival; D019583:Dose Fractionation, Radiation; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy / Q000601:surgery; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000601:surgery; D016634:Radiosurgery / Q000009:adverse effects / Q000379:methods; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors
chemical_list: D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D042461:Vascular Endothelial Growth Factor A; D000068258:Bevacizumab