title: Local convection enhanced delivery of IL4-Pseudomonas exotoxin (NBI-3001) for treatment of patients with recurrent malignant glioma.
abstract: OBJECTIVE
  This was an open-label, dose-escalation trial of intratumoral administration of IL-4 Pseudomonas Exotoxin (NBI-3001) in patients with recurrent malignant glioma.
  
  
  METHODS
  A total of 31 patients with histologically verified supratentorial grade 3 and 4 astrocytoma were studied. Of these, twenty-five patients were diagnosed with glioblastoma multiforme (GBM) while six were diagnosed with anaplastic astrocytoma (AA). Patients were over 18 years of age and had Karnofsky performance scores > or = 60. Patients were assigned to one of four dose groups in a dose-escalation fashion: 6 microg/ml x 40 ml, 9 microg/ml x 40 ml, 15 microg/ml x 40 ml, or 9 microg/ml x 100 ml of NBI-3001 administered intratumorally via stereotactically placed catheters. Patients were followed with serial MRI scans and clinical assessments every four weeks for the first 16 weeks and then every eight weeks until week 26.
  
  
  RESULTS
  No drug-related systemic toxicity, as evident by lack of hematological or serum chemical changes, was apparent in any patients; treatment-related adverse effects were limited to the central nervous system. No deaths were attributable to treatment. Drug-related Grade 3 or 4 toxicity was seen in 39% of patients in all dose groups and 22% of patients at the maximum tolerated dose of 6 microg/ml x 40 ml. The overall median survival was 8.2 months with a median survival of 5.8 months for the GBM patients. Six-month survival was 52% and 48%, respectively. Gadolinium-enhanced magnetic resonance imaging of the brain showed areas of decreased signal intensity within the tumor consistent with tumor necrosis following treatment in many patients.
  
  
  CONCLUSIONS
  NBI-3001 appears to have an acceptable safety and toxicity profile when administered intratumorally in patients with recurrent malignant glioma.
authors.affiliation: Department of Neurological Surgery, Heinrich Heine University, Düsseldorf, Germany. fweber@Klinikum-saarbruecken.de
authors.forename: F W
authors.initials: FW
authors.lastname: Weber
authors.forename: F
authors.initials: F
authors.lastname: Floeth
authors.forename: A
authors.initials: A
authors.lastname: Asher
authors.forename: R
authors.initials: R
authors.lastname: Bucholz
authors.forename: M
authors.initials: M
authors.lastname: Berger
authors.forename: M
authors.initials: M
authors.lastname: Prados
authors.forename: S
authors.initials: S
authors.lastname: Chang
authors.forename: J
authors.initials: J
authors.lastname: Bruce
authors.forename: W
authors.initials: W
authors.lastname: Hall
authors.forename: N G
authors.initials: NG
authors.lastname: Rainov
authors.forename: M
authors.initials: M
authors.lastname: Westphal
authors.forename: R E
authors.initials: RE
authors.lastname: Warnick
authors.forename: R W
authors.initials: RW
authors.lastname: Rand
authors.forename: F
authors.initials: F
authors.lastname: Rommell
authors.forename: H
authors.initials: H
authors.lastname: Pan
authors.forename: V N
authors.initials: VN
authors.lastname: Hingorani
authors.forename: R K
authors.initials: RK
authors.lastname: Puri
mesh_terms: D000328:Adult; D000368:Aged; D001254:Astrocytoma / Q000175:diagnosis / Q000188:drug therapy*; D001427:Bacterial Toxins / Q000008:administration & dosage* / Q000009:adverse effects; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D004305:Dose-Response Relationship, Drug; D005098:Exotoxins / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D005909:Glioblastoma / Q000175:diagnosis / Q000188:drug therapy*; D006801:Humans; D000922:Immunotoxins / Q000008:administration & dosage* / Q000009:adverse effects; D036502:Infusions, Intralesional; D015847:Interleukin-4 / Q000008:administration & dosage* / Q000009:adverse effects; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis / Q000188:drug therapy*; D011446:Prospective Studies; D013238:Stereotaxic Techniques; D015173:Supratentorial Neoplasms / Q000175:diagnosis / Q000188:drug therapy*
chemical_list: D001427:Bacterial Toxins; D005098:Exotoxins; D000922:Immunotoxins; C479467:interleukin-4-Pseudomonas exotoxin; D015847:Interleukin-4