title: Iodine-131-labeled antitenascin monoclonal antibody 81C6 treatment of patients with recurrent malignant gliomas: phase I trial results.
abstract: OBJECTIVE
  To determine the maximum-tolerated dose (MTD) of iodine 131 (131I)-labeled 81C6 monoclonal antibody (mAb) in brain tumor patients with surgically created resection cavities (SCRCs) and to identify any objective responses to this treatment.
  
  
  METHODS
  In this phase I trial, eligible patients were treated with a single injection of 131I-labeled 81C6. Cohorts of three to six patients were treated with escalating dosages of 131I (starting dose of 20 mCi with a 20-mCi escalation in subsequent cohorts) administered through an Ommaya reservoir in the SCRC. Patients were followed up for toxicity and response until death or for a minimum of 1 year after treatment. The SCRC patients, who were previously irradiated, were followed up without additional treatment unless progressive disease was identified.
  
  
  RESULTS
  We administered 36 treatments of 131I doses up to 120 mCi to 34 previously irradiated patients with recurrent or metastatic brain tumors. Dose-limiting toxicity was reached at 120 mCi and was limited to neurologic or hematologic toxicity. None of the patients treated with less than 120 mCi developed significant neurologic toxicity; one patient developed major hematologic toxicity (MHT). The estimated median survival for patients with glioblastoma multiforme (GBM) and for all patients was 56 and 60 weeks, respectively.
  
  
  CONCLUSIONS
  The MTD for administration of 131I-labeled 81C6 into the SCRCs of previously irradiated patients with recurrent primary or metastatic brain tumors was 100 mCi. The dose-limiting toxicity was neurologic toxicity. We are encouraged by the minimal toxicity and survival in this phase I trial. Radiolabeled mAbs may improve the current therapy for brain tumor patients.
authors.affiliation: Department of Pathology, Duke University Medical Center, Durham, NC 27710, USA. bigne001@mc.duke.edu
authors.forename: D D
authors.initials: DD
authors.lastname: Bigner
authors.forename: M T
authors.initials: MT
authors.lastname: Brown
authors.forename: A H
authors.initials: AH
authors.lastname: Friedman
authors.forename: R E
authors.initials: RE
authors.lastname: Coleman
authors.forename: G
authors.initials: G
authors.lastname: Akabani
authors.forename: H S
authors.initials: HS
authors.lastname: Friedman
authors.forename: W L
authors.initials: WL
authors.lastname: Thorstad
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: C N
authors.initials: CN
authors.lastname: Pegram
authors.forename: C J
authors.initials: CJ
authors.lastname: Wikstrand
authors.forename: J E
authors.initials: JE
authors.lastname: Herndon
authors.forename: N A
authors.initials: NA
authors.lastname: Vick
authors.forename: N
authors.initials: N
authors.lastname: Paleologos
authors.forename: I
authors.initials: I
authors.lastname: Cokgor
authors.forename: J M
authors.initials: JM
authors.lastname: Provenzale
authors.forename: M R
authors.initials: MR
authors.lastname: Zalutsky
mesh_terms: D000293:Adolescent; D000328:Adult; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D001706:Biopsy; D001932:Brain Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D002648:Child; D005260:Female; D005910:Glioma / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D006801:Humans; D007118:Immunoassay; D007167:Immunotherapy; D015552:Injections, Intralesional; D007457:Iodine Radioisotopes; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000628:therapy; D009422:Nervous System Diseases / Q000139:chemically induced; D015996:Survival Rate; D019063:Tenascin / Q000276:immunology*; D014055:Tomography, Emission-Computed; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D007457:Iodine Radioisotopes; D019063:Tenascin