Journal of Clinical Oncology, Vol 16, 2202-2212, Copyright © 1998 by American Society of Clinical Oncology

ARTICLES

Iodine-131-labeled antitenascin monoclonal antibody 81C6 treatment of patients with recurrent malignant gliomas: phase I trial results

DD Bigner, MT Brown, AH Friedman, RE Coleman, G Akabani, HS Friedman, WL Thorstad, RE McLendon, SH Bigner, XG Zhao, CN Pegram, CJ Wikstrand, JE Herndon 2nd, NA Vick, N Paleologos, I Cokgor, JM Provenzale and MR Zalutsky
Department of Pathology, Duke University Medical Center, Durham, NC 27710, USA. bigne001@mc.duke.edu

PURPOSE: To determine the maximum-tolerated dose (MTD) of iodine 131 (131I)-labeled 81C6 monoclonal antibody (mAb) in brain tumor patients with surgically created resection cavities (SCRCs) and to identify any objective responses to this treatment. METHODS: In this phase I trial, eligible patients were treated with a single injection of 131I-labeled 81C6. Cohorts of three to six patients were treated with escalating dosages of 131I (starting dose of 20 mCi with a 20-mCi escalation in subsequent cohorts) administered through an Ommaya reservoir in the SCRC. Patients were followed up for toxicity and response until death or for a minimum of 1 year after treatment. The SCRC patients, who were previously irradiated, were followed up without additional treatment unless progressive disease was identified. RESULTS: We administered 36 treatments of 131I doses up to 120 mCi to 34 previously irradiated patients with recurrent or metastatic brain tumors. Dose-limiting toxicity was reached at 120 mCi and was limited to neurologic or hematologic toxicity. None of the patients treated with less than 120 mCi developed significant neurologic toxicity; one patient developed major hematologic toxicity (MHT). The estimated median survival for patients with glioblastoma multiforme (GBM) and for all patients was 56 and 60 weeks, respectively. CONCLUSION: The MTD for administration of 131I-labeled 81C6 into the SCRCs of previously irradiated patients with recurrent primary or metastatic brain tumors was 100 mCi. The dose- limiting toxicity was neurologic toxicity. We are encouraged by the minimal toxicity and survival in this phase I trial. Radiolabeled mAbs may improve the current therapy for brain tumor patients.
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