title: Intra-arterial delivery of bevacizumab after blood-brain barrier disruption for the treatment of recurrent glioblastoma: progression-free survival and overall survival.
abstract: BACKGROUND
  This prospective, single-center study assesses progression-free survival (PFS) and overall survival (OS) in patients with recurrent glioblastoma multiforme (GBM) treated with a single dose of superselective intra-arterial cerebral infusion (SIACI) of bevacizumab (BV) after blood-brain barrier disruption (BBBD). Patients were initially enrolled in our phase I study, for which the primary end point was to determine the safety and maximum tolerated dose of SIACI BV.
  
  
  METHODS
  Fourteen patients with recurrent GBM were recruited between August 2009 and November 2010 after failing the standard treatment with radiation therapy and temozolomide. None of these patients were previously treated with BV. After receiving a single dose of IA BV (2 to 15 mg/kg), standard IV BV chemotherapy was continued in 12 of 14 patients (86%). The recently updated Response Assessment in Neuro-Oncology Working Group (RANO) criteria were used to evaluate PFS, and the Kaplan-Meier estimator was used to evaluate PFS and OS.
  
  
  RESULTS
  Using RANO criteria, the median PFS in these patients was 10 months. The median OS estimation for this cohort was 8.8 months. The OS was less than the PFS because 4 patients died without progressing. Toxicity attributed to the IA BV treatment was present in 2 patients (wound dehiscence and rash). Another patient suffered from seizures 1 week after the SIACI procedure; however, this patient had epilepsy before and seizure type/frequency were similar before and after therapy.
  
  
  CONCLUSIONS
  Our study shows that for patients naïve to BV, a single dose of SIACI BV after BBBD followed by IV BV offers an encouraging outcome in terms of PFS when compared with previous trials using IV BV with and without concomitant irinotecan (CPT-11). Larger phase II trials are warranted to determine whether repeated IA BV alone is superior to IV BV for recurrent GBM.
authors.affiliation: Department of Neurological Surgery, New York-Presbyterian Hospital, Weill Cornell Medical College, New York, New York, USA.
authors.forename: Jan-Karl
authors.initials: JK
authors.lastname: Burkhardt
authors.forename: Howard
authors.initials: H
authors.lastname: Riina
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Shin
authors.forename: Paul
authors.initials: P
authors.lastname: Christos
authors.forename: Kartik
authors.initials: K
authors.lastname: Kesavabhotla
authors.forename: Christoph P
authors.initials: CP
authors.lastname: Hofstetter
authors.forename: Apostolos John
authors.initials: AJ
authors.lastname: Tsiouris
authors.forename: John A
authors.initials: JA
authors.lastname: Boockvar
mesh_terms: D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab; D001812:Blood-Brain Barrier / Q000502:physiology*; D001932:Brain Neoplasms / Q000601:surgery*; D015331:Cohort Studies; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D005909:Glioblastoma / Q000601:surgery*; D006801:Humans; D007261:Infusions, Intra-Arterial; D053208:Kaplan-Meier Estimate; D017567:Karnofsky Performance Status; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D011183:Postoperative Complications / Q000517:prevention & control*; D012640:Seizures / Q000150:complications; D013529:Surgical Wound Dehiscence / Q000188:drug therapy; D016896:Treatment Outcome
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab