title: Durability of single dose intra-arterial bevacizumab after blood/brain barrier disruption for recurrent glioblastoma.
abstract: BACKGROUND
  Bevacizumab (BV) has been used to treat recurrent glioblastoma with a progression free survival of approximately 3-3.5 months. Typically, it is administered intravenously every 2-3 weeks at dosages ranging from 5-15 mg/kg. Serious side effects include GI tract perforations, hematologic disorders, intracranial hemorrhage, and malignant hypertension. We hypothesized that selective intracranial intra-arterial infusion (SIACI) of BV following blood/brain barrier disruption (BBBD) with mannitol may allow for reduced dosage, lower toxicity, and equivalent or superior progression free survival (PFS).
  
  
  METHODS
  Sixteen patients (8 males & 8 females) with a mean age of 55 years (range 27-68), KPS>70, and recurrent glioblastoma were enrolled. All patients underwent super-selective catheterization and were given a single intra-arterial dose of 15 mg/kg BV following osmotic blood/brain barrier disruption with mannitol to the arteries supplying the tumor. The patients had no additional treatment following that initial SIACI mannitol and BV until they met criteria for progression. PFS was assessed using modified Response Assessment in Neuro-Oncology (RANO) criteria.
  
  
  RESULTS
  Median progression free survival from only one dose of SIACI mannitol and BV was 3.9 months. Side effects included seizure in 2 patients, and headache in 1 patient. Seizures were well controlled with medications, and there were no serious toxicities. There were no endovascular-related complications.
  
  
  CONCLUSIONS
  SIACI of mannitol and BV at 15mg/kg allows for similar or better PFS compared to biweekly treatments of IV BV at 10mg/kg. The dosage required is lower and side effects were minimal and well tolerated. Future larger trials are warranted to assess whether repeated less frequent IA mannitol and BV may be superior to biweekly IV administration as a monotherapy.
authors.affiliation: Brain Tumor Center, Department of Neurosurgery, Lenox Hill Hospital, New York, NY, USA.|Departments of Neurosurgery.
authors.forename: Shamik
authors.initials: S
authors.lastname: Chakraborty
authors.affiliation: Brain Tumor Center, Department of Neurosurgery, Lenox Hill Hospital, New York, NY, USA.|Radiology, Hofstra Northwell School of Medicine, Manhasset, NY, USA.
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Filippi
authors.affiliation: Department of Neurosurgery, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
authors.forename: Jan-Karl
authors.initials: JK
authors.lastname: Burkhardt
authors.affiliation: Brain Tumor Center, Department of Neurosurgery, Lenox Hill Hospital, New York, NY, USA.
authors.forename: Sherese
authors.initials: S
authors.lastname: Fralin
authors.affiliation: Brain Tumor Center, Department of Neurosurgery, Lenox Hill Hospital, New York, NY, USA.
authors.forename: Ashley
authors.initials: A
authors.lastname: Ray
authors.affiliation: Brain Tumor Center, Department of Neurosurgery, Lenox Hill Hospital, New York, NY, USA.
authors.forename: Tamika
authors.initials: T
authors.lastname: Wong
authors.affiliation: Brain Tumor Center, Department of Neurosurgery, Lenox Hill Hospital, New York, NY, USA.|Departments of Neurosurgery.
authors.forename: Rafael
authors.initials: R
authors.lastname: Ortiz
authors.affiliation: Brain Tumor Center, Department of Neurosurgery, Lenox Hill Hospital, New York, NY, USA.|Departments of Neurosurgery.
authors.forename: David J
authors.initials: DJ
authors.lastname: Langer
authors.affiliation: Brain Tumor Center, Department of Neurosurgery, Lenox Hill Hospital, New York, NY, USA.|Departments of Neurosurgery.
authors.forename: John A
authors.initials: JA
authors.lastname: Boockvar
mesh_terms: D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage*; D000068258:Bevacizumab / Q000008:administration & dosage*; D001812:Blood-Brain Barrier / Q000187:drug effects*; D001932:Brain Neoplasms / Q000188:drug therapy*; D018572:Disease-Free Survival; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy*; D006801:Humans; D007261:Infusions, Intra-Arterial / Q000379:methods; D008297:Male; D008353:Mannitol / Q000627:therapeutic use; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*
chemical_list: D020533:Angiogenesis Inhibitors; D000068258:Bevacizumab; D008353:Mannitol
keywords: bevacizumab; blood brain barrier; brain tumors; glioblastoma; intraarterial