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.
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.
Reardon
David A
DA
Department of Surgery, Division of Neurosurgery, Duke University Medical Center, Durham, NC, 27710, USA. reard003@mc.duke.edu
Akabani
Gamal
G
Coleman
R Edward
RE
Friedman
Allan H
AH
Friedman
Henry S
HS
Herndon
James E
JE
McLendon
Roger E
RE
Pegram
Charles N
CN
Provenzale
James M
JM
Quinn
Jennifer A
JA
Rich
Jeremy N
JN
Vredenburgh
James J
JJ
Desjardins
Annick
A
Gururangan
Sridharan
S
Guruangan
Sri
S
Badruddoja
Michael
M
Dowell
Jeanette M
JM
Wong
Terence Z
TZ
Zhao
Xiao-Guang
XG
Zalutsky
Michael R
MR
Bigner
Darell D
DD
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*
D000911:Antibodies, Monoclonal; D007457:Iodine Radioisotopes; D019063:Tenascin