title: Salvage radioimmunotherapy with murine iodine-131-labeled antitenascin monoclonal antibody 81C6 for patients with recurrent primary and metastatic malignant brain tumors: phase II study results.
abstract: OBJECTIVE
  To assess the efficacy and toxicity of intraresection cavity iodine-131-labeled murine antitenascin monoclonal antibody 81C6 (131I-m81C6) among recurrent malignant brain tumor patients.
  
  
  METHODS
  In this phase II trial, 100 mCi of 131I-m81C6 was injected directly into the surgically created resection cavity (SCRC) of 43 patients with recurrent malignant glioma (glioblastoma multiforme [GBM], n = 33; anaplastic astrocytoma [AA], n = 6; anaplastic oligodendroglioma [AO], n = 2; gliosarcoma [GS], n = 1; and metastatic adenocarcinoma, n = 1) followed by chemotherapy.
  
  
  RESULTS
  With a median follow-up of 172 weeks, 63% and 59% of patients with GBM/GS and AA/AO tumors were alive at 1 year. Median overall survival for patients with GBM/GS and AA/AO tumors was 64 and 99 weeks, respectively. Ten patients (23%) developed acute hematologic toxicity. Five patients (12%) developed acute reversible neurotoxicity. One patient (2%) developed irreversible neurotoxicity. No patients required reoperation for radionecrosis.
  
  
  CONCLUSIONS
  In this single-institution phase II study, administration of 100 mCi of 131I-m81C6 to recurrent malignant glioma patients followed by chemotherapy is associated with a median survival that is greater than that of historical controls treated with surgery plus iodine-125 brachytherapy. Furthermore, toxicity was acceptable. Administration of a fixed millicurie dose resulted in a wide range of absorbed radiation doses to the SCRC. We are now conducting a phase II trial, approved by the US Food and Drug Administration, using patient-specific 131I-m81C6 dosing, to deliver 44 Gy to the SCRC followed by standardized chemotherapy. A phase III multicenter trial with patient-specific dosing is planned.
authors.affiliation: Department of Surgery, Division of Neurosurgery, Duke University Medical Center, Durham, NC, 27710, USA. reard003@mc.duke.edu
authors.forename: David A
authors.initials: DA
authors.lastname: Reardon
authors.forename: Gamal
authors.initials: G
authors.lastname: Akabani
authors.forename: R Edward
authors.initials: RE
authors.lastname: Coleman
authors.forename: Allan H
authors.initials: AH
authors.lastname: Friedman
authors.forename: Henry S
authors.initials: HS
authors.lastname: Friedman
authors.forename: James E
authors.initials: JE
authors.lastname: Herndon
authors.forename: Roger E
authors.initials: RE
authors.lastname: McLendon
authors.forename: Charles N
authors.initials: CN
authors.lastname: Pegram
authors.forename: James M
authors.initials: JM
authors.lastname: Provenzale
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Quinn
authors.forename: Jeremy N
authors.initials: JN
authors.lastname: Rich
authors.forename: James J
authors.initials: JJ
authors.lastname: Vredenburgh
authors.forename: Annick
authors.initials: A
authors.lastname: Desjardins
authors.forename: Sridharan
authors.initials: S
authors.lastname: Gururangan
authors.forename: Sri
authors.initials: S
authors.lastname: Guruangan
authors.forename: Michael
authors.initials: M
authors.lastname: Badruddoja
authors.forename: Jeanette M
authors.initials: JM
authors.lastname: Dowell
authors.forename: Terence Z
authors.initials: TZ
authors.lastname: Wong
authors.forename: Xiao-Guang
authors.initials: XG
authors.lastname: Zhao
authors.forename: Michael R
authors.initials: MR
authors.lastname: Zalutsky
authors.forename: Darell D
authors.initials: DD
authors.lastname: Bigner
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001706:Biopsy; D001932:Brain Neoplasms / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D005260:Female; D006801:Humans; D007457:Iodine Radioisotopes / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000532:radiotherapy*; D016499:Radioimmunotherapy / Q000009:adverse effects; D016879:Salvage Therapy; D019063:Tenascin / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D007457:Iodine Radioisotopes; D019063:Tenascin