title: Phase I trial results of iodine-131-labeled antitenascin monoclonal antibody 81C6 treatment of patients with newly diagnosed malignant gliomas.
abstract: OBJECTIVE
  To determine the maximum-tolerated dose (MTD) of iodine-131 ((131)I)-labeled 81C6 antitenascin monoclonal antibody (mAb) administered clinically into surgically created resection cavities (SCRCs) in malignant glioma patients and to identify any objective responses with this treatment.
  
  
  METHODS
  In this phase I trial, newly diagnosed patients with malignant gliomas with no prior external-beam therapy or chemotherapy were treated with a single injection of (131)I-labeled 81C6 through a Rickham reservoir into the resection cavity. The initial dose was 20 mCi and escalation was in 20-mCi increments. Patients were observed for toxicity and response until death or for a minimum of 1 year after treatment.
  
  
  RESULTS
  We treated 42 patients with (131)I-labeled 81C6 mAb in administered doses up to 180 mCi. Dose-limiting toxicity was observed at doses greater than 120 mCi and consisted of delayed neurotoxicity. None of the patients developed major hematologic toxicity. Median survival for patients with glioblastoma multiforme and for all patients was 69 and 79 weeks, respectively.
  
  
  CONCLUSIONS
  The MTD for administration of (131)I-labeled 81C6 into the SCRC of newly diagnosed patients with no prior radiation therapy or chemotherapy was 120 mCi. Dose-limiting toxicity was delayed neurologic toxicity. We are encouraged by the survival and toxicity and by the low 2.5% prevalence of debulking surgery for symptomatic radiation necrosis.
authors.affiliation: Department of Pathology, Duke University Medical Center, Durham, NC 27710, USA. cokgo001@mc.duke.edu
authors.forename: I
authors.initials: I
authors.lastname: Cokgor
authors.forename: G
authors.initials: G
authors.lastname: Akabani
authors.forename: C T
authors.initials: CT
authors.lastname: Kuan
authors.forename: H S
authors.initials: HS
authors.lastname: Friedman
authors.forename: A H
authors.initials: AH
authors.lastname: Friedman
authors.forename: R E
authors.initials: RE
authors.lastname: Coleman
authors.forename: R E
authors.initials: RE
authors.lastname: McLendon
authors.forename: S H
authors.initials: SH
authors.lastname: Bigner
authors.forename: X G
authors.initials: XG
authors.lastname: Zhao
authors.forename: A M
authors.initials: AM
authors.lastname: Garcia-Turner
authors.forename: C N
authors.initials: CN
authors.lastname: Pegram
authors.forename: C J
authors.initials: CJ
authors.lastname: Wikstrand
authors.forename: T D
authors.initials: TD
authors.lastname: Shafman
authors.forename: J E
authors.initials: JE
authors.lastname: Herndon
authors.forename: J M
authors.initials: JM
authors.lastname: Provenzale
authors.forename: M R
authors.initials: MR
authors.lastname: Zalutsky
authors.forename: D D
authors.initials: DD
authors.lastname: Bigner
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D005260:Female; D005500:Follow-Up Studies; D005910:Glioma / Q000000981:diagnostic imaging / Q000532:radiotherapy* / Q000601:surgery; D006801:Humans; D000922:Immunotoxins / Q000009:adverse effects / Q000627:therapeutic use*; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D015173:Supratentorial Neoplasms / Q000000981:diagnostic imaging / Q000532:radiotherapy* / Q000601:surgery; D016019:Survival Analysis; D019063:Tenascin / Q000276:immunology*; D014055:Tomography, Emission-Computed
chemical_list: D000911:Antibodies, Monoclonal; D000922:Immunotoxins; D019063:Tenascin