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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

From the Departments of Surgery, Medicine, Pathology, Radiology, and Cancer Center Biostatistics, Duke University Medical Center, Durham, NC.

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

PURPOSE: 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.

PATIENTS AND 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.

CONCLUSION: 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.

Supported by National Institutes of Health Grants No. 1-P50-CA108786-01, NS20023 and CA11898 and by Grant No. MO1 RR 30 through the General Clinical Research Centers Program, National Center for Research Resources, National Institutes of Health.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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