title: Safety, tolerability, and tumor response of IL4-Pseudomonas exotoxin (NBI-3001) in 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 grades 3 and 4 astrocytoma were studied. Of these, 25 patients were diagnosed with glioblastoma multiforme (GBM) while six were diagnosed with anaplastic astrocytoma. 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 via convection-enhanced delivery intratumorally using 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.
authors.forename: Friedrich
authors.initials: F
authors.lastname: Weber
authors.forename: Anthony
authors.initials: A
authors.lastname: Asher
authors.forename: Richard
authors.initials: R
authors.lastname: Bucholz
authors.forename: Mitchel
authors.initials: M
authors.lastname: Berger
authors.forename: Michael
authors.initials: M
authors.lastname: Prados
authors.forename: Susan
authors.initials: S
authors.lastname: Chang
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Bruce
authors.forename: Walter
authors.initials: W
authors.lastname: Hall
authors.forename: Nikolai G
authors.initials: NG
authors.lastname: Rainov
authors.forename: Manfred
authors.initials: M
authors.lastname: Westphal
authors.forename: Ronald E
authors.initials: RE
authors.lastname: Warnick
authors.forename: Robert W
authors.initials: RW
authors.lastname: Rand
authors.forename: Frank
authors.initials: F
authors.lastname: Floeth
authors.forename: Frank
authors.initials: F
authors.lastname: Rommel
authors.forename: Henry
authors.initials: H
authors.lastname: Pan
authors.forename: Vijay N
authors.initials: VN
authors.lastname: Hingorani
authors.forename: Raj K
authors.initials: RK
authors.lastname: Puri
mesh_terms: D000328:Adult; D000368:Aged; D000906:Antibodies / Q000032:analysis; D001254:Astrocytoma / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D001427:Bacterial Toxins / Q000009:adverse effects / Q000097:blood / Q000276:immunology / Q000627:therapeutic use*; D002528:Cerebellar Neoplasms / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005098:Exotoxins / Q000009:adverse effects / Q000097:blood / Q000276:immunology / Q000627:therapeutic use*; D005260:Female; D005909:Glioblastoma / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D006801:Humans; D015847:Interleukin-4 / Q000009:adverse effects / Q000097:blood / Q000276:immunology / Q000627:therapeutic use*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D012449:Safety; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000906:Antibodies; D001427:Bacterial Toxins; D005098:Exotoxins; C479467:interleukin-4-Pseudomonas exotoxin; D015847:Interleukin-4