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Phase II Trial of Murine ¹³¹I-Labeled Antitenascin Monoclonal Antibody 81C6 Administered Into Surgically Created Resection Cavities of Patients With Newly Diagnosed Malignant Gliomas

From the Departments of Surgery, Medicine, Pathology, Radiology, and Biostatistics and Bioinformatics, Duke University Medical Center, Durham, NC; and Department of Medicine, University of California at Davis Medical Center, San Rafael, CA.

Address reprint requests to David A. Reardon, MD, Department of Surgery, Division of Neurosurgery, Duke University Medical Center, Box 3624, Durham, NC, 27710; email: reard003{at}mc.duke.edu

PURPOSE: To assess the efficacy and toxicity of intraresection cavity ¹³¹I-labeled murine antitenascin monoclonal antibody 81C6 and determine its true response rate among patients with newly diagnosed malignant glioma.

PATIENTS AND METHODS: In this phase II trial, 120 mCi of ¹³¹I-labeled murine 81C6 was injected directly into the surgically created resection cavity of 33 patients with previously untreated malignant glioma (glioblastoma multiforme [GBM], n = 27; anaplastic astrocytoma, n = 4; anaplastic oligodendroglioma, n = 2). Patients then received conventional external-beam radiotherapy followed by a year of alkylator-based chemotherapy.

RESULTS: Median survival for all patients and those with GBM was 86.7 and 79.4 weeks, respectively. Eleven patients remain alive at a median follow-up of 93 weeks (range, 49 to 220 weeks). Nine patients (27%) developed reversible hematologic toxicity, and histologically confirmed, treatment-related neurologic toxicity occurred in five patients (15%). One patient (3%) required reoperation for radionecrosis.

CONCLUSION: Median survival achieved with ¹³¹I-labeled 81C6 exceeds that of historical controls treated with conventional radiotherapy and chemotherapy, even after accounting for established prognostic factors including age and Karnofsky performance status. The median survival achieved with ¹³¹I-labeled 81C6 compares favorably with either ¹²⁵I interstitial brachy-therapy or stereotactic radiosurgery and is associated with a significantly lower rate of reoperation for radionecrosis. Our results confirm the efficacy of ¹³¹I-labeled 81C6 for patients with newly diagnosed malignant glioma and suggest that a randomized phase III study is indicated.

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