title: Superselective intraarterial cerebral infusion of cetuximab after osmotic blood/brain barrier disruption for recurrent malignant glioma: phase I study.
abstract: Objective To establish a maximum tolerated dose of superselective intraarterial cerebral infusion (SIACI) of Cetuximab after osmotic disruption of the blood-brain barrier (BBB) with mannitol, and examine safety of the procedure in patients with recurrent malignant glioma. Methods A total of 15 patients with recurrent malignant glioma were included in the current study. The starting dose of Cetuximab was 100 mg/m(2) and dose escalation was done to 250 mg/m(2). All patients were observed for 28 days post-infusion for any side effects. Results There was no dose-limiting toxicity from a single dose of SIACI of Cetuximab up to 250 mg/m(2) after osmotic BBB disruption with mannitol. A tolerable rash was seen in 2 patients, anaphylaxis in 1 patient, isolated seizure in 1 patient, and seizure and cerebral edema in 1 patient. Discussion SIACI of mannitol followed by Cetuximab (up to 250 mg/m(2)) for recurrent malignant glioma is safe and well tolerated. A Phase I/II trial is currently underway to determine the efficacy of SIACI of cetuximab in patients with high-grade glioma.
authors.affiliation: Lenox Hill Brain Tumor Center, Lenox Hill Hospital, Northwell Health, New York, NY, USA.|Departments of Neurosurgery, Neurology, Radiology, and Pathology, Hofstra Northwell School of Medicine, Manhasset, NY, USA.
authors.forename: Shamik
authors.identifier: 0000-0002-8627-6598
authors.initials: S
authors.lastname: Chakraborty
authors.affiliation: Departments of Neurosurgery, Neurology, Radiology, and Pathology, Hofstra Northwell School of Medicine, Manhasset, NY, USA.
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Filippi
authors.affiliation: Lenox Hill Brain Tumor Center, Lenox Hill Hospital, Northwell Health, New York, NY, USA.
authors.forename: Tamika
authors.initials: T
authors.lastname: Wong
authors.affiliation: Lenox Hill Brain Tumor Center, Lenox Hill Hospital, Northwell Health, New York, NY, USA.
authors.forename: Ashley
authors.initials: A
authors.lastname: Ray
authors.affiliation: Lenox Hill Brain Tumor Center, Lenox Hill Hospital, Northwell Health, New York, NY, USA.
authors.forename: Sherese
authors.initials: S
authors.lastname: Fralin
authors.affiliation: Departments of Neurosurgery and Radiology, Weill Cornell Medical College of Cornell University, New York, NY, USA.
authors.forename: A John
authors.initials: AJ
authors.lastname: Tsiouris
authors.affiliation: Departments of Neurosurgery, Neurology, Radiology, and Pathology, Hofstra Northwell School of Medicine, Manhasset, NY, USA.
authors.forename: Bidyut
authors.initials: B
authors.lastname: Praminick
authors.affiliation: Lenox Hill Brain Tumor Center, Lenox Hill Hospital, Northwell Health, New York, NY, USA.|Departments of Neurosurgery, Neurology, Radiology, and Pathology, Hofstra Northwell School of Medicine, Manhasset, NY, USA.
authors.forename: Alexis
authors.initials: A
authors.lastname: Demopoulos
authors.affiliation: Departments of Neurosurgery and Radiology, Weill Cornell Medical College of Cornell University, New York, NY, USA.
authors.forename: Heather J
authors.initials: HJ
authors.lastname: McCrea
authors.affiliation: Lenox Hill Brain Tumor Center, Lenox Hill Hospital, Northwell Health, New York, NY, USA.
authors.forename: Imithri
authors.initials: I
authors.lastname: Bodhinayake
authors.affiliation: Lenox Hill Brain Tumor Center, Lenox Hill Hospital, Northwell Health, New York, NY, USA.|Departments of Neurosurgery, Neurology, Radiology, and Pathology, Hofstra Northwell School of Medicine, Manhasset, NY, USA.
authors.forename: Rafael
authors.initials: R
authors.lastname: Ortiz
authors.affiliation: Lenox Hill Brain Tumor Center, Lenox Hill Hospital, Northwell Health, New York, NY, USA.|Departments of Neurosurgery, Neurology, Radiology, and Pathology, Hofstra Northwell School of Medicine, Manhasset, NY, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Langer
authors.affiliation: Lenox Hill Brain Tumor Center, Lenox Hill Hospital, Northwell Health, New York, NY, USA. jboockvar@nshs.edu.|Departments of Neurosurgery, Neurology, Radiology, and Pathology, Hofstra Northwell School of Medicine, Manhasset, NY, USA. jboockvar@nshs.edu.|Department of Neurological Surgery, Hofstra Northwell School of Medicine, Manhasset, NY, USA. jboockvar@nshs.edu.
authors.forename: John A
authors.initials: JA
authors.lastname: Boockvar
mesh_terms: D000328:Adult; D000368:Aged; D000074322:Antineoplastic Agents, Immunological / Q000008:administration & dosage* / Q000009:adverse effects; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism; D001932:Brain Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000378:metabolism; D000068818:Cetuximab / Q000008:administration & dosage* / Q000009:adverse effects; D004234:Diuretics, Osmotic / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D005910:Glioma / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D007261:Infusions, Intra-Arterial; D008297:Male; D008353:Mannitol / Q000627:therapeutic use*; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D000074322:Antineoplastic Agents, Immunological; D004234:Diuretics, Osmotic; D008353:Mannitol; D000068818:Cetuximab
keywords: Brain neoplasm; Cetuximab; Glioma; Intraarterial infusion; Mannitol