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Phase
I trial results of iodine-131-labeled antitenascin monoclonal antibody 81C6
treatment of patients with newly diagnosed malignant brain tumors following
external beam radiotherapy
David
Reardon, Gamal Akabani, Allan Friedman, Henry Friedman, James Herndon II, Ilkcan
Cokgor, Roger McLendon, Jennifer Quinn, Jeremy Rich, Kara Penne, John Sampson,
Timothy Shafman, Terence Wong, Michael Zalutsky, Darell D Bigner
Duke Univ
Med Ctr, Durham, NC; Univ of California Santa Barbara, Santa Barbara, CA
This
Phase I trial was performed to determine the maximum tolerated dose (MTD) of
Iodine-131 murine 81C6 monoclonal antibody (MAb) administered via surgically
created resection cavities to patients with newly diagnosed malignant brain
tumors following external beam radiotherapy.
Following a gross total resection and documentation of tumor anti-tenascin
immunoreactivity, patients received 131I-81C6 through a Rickham reservoir.
The initial dose was 20 mCi, and this was escalated in 20-mCi increments.
One month following MAb administration, patients began a year of chemotherapy.
Twenty-two patients were treated (glioblastoma multiforme (GBM), n=15;
anaplastic astrocytoma, n=4; anaplastic oligodendroglioma, n=2; metastatic
melanoma, n=1) at the following dose levels: 20 mCi (n=1); 40 mCi (n=2); 60 mCi
(n=2); 80 mCi (n=3); 100 mCi (n=6); 120 mCi (n=5); and 140 mCi (n=3).
Fifteen were male.
Median age was 44 years (range, 23-61); the average KPS was 83% (range, 70-100).
Four patients given 120 mCi developed dose-limiting toxicity (DLT): grade 4
hematologic toxicity for more than 2 weeks (n=2); grade 3-4 neurologic toxicity
(n=2).
Single episodes of hematologic DLT and grade 3 neurologic toxicity occurred at
the 140-mCi dose level.
Median survival was 54 weeks among all patients and 53 weeks for those with GBM.
Our results demonstrate that the MTD of 131I-81C6 MAb therapy for patients with
newly diagnosed malignant brain tumors following external beam radiotherapy is
100 mCi.
Median survival was encouraging and suggests that a Phase II trial is indicated.
© Copyright 2002
American
Society of Clinical Oncology
Source: http://www.asco.org/ac/1,1003,_12-002324-00_18-002002-00_19-002113-00_29-00A-00_42-00ONeill-00_43-00-00_44-00-00_45-00
Author-00_46-00Title-00_47-00Title-00_48-00and-00_49-00and,00.asp?cat=CNS+Tumors&parent=CENTRAL+NERVOUS+SYSTEM+TUMORS
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