Phase I trial results of iodine-131-labeled antitenascin monoclonal antibody 81C6 treatment of patients with newly diagnosed malignant gliomas

Purpose: To determine the maximum-tolerated dose (MTD) of iodine-131 (I-131 )-labeled 81C6 antitenascin monoclonal antibody (mAb) administered clinical ly into surgically created resection cavities (SCRCs) in malignant glioma p atients and to identify any objective responses with this treatment. Patients and Methods: In this phase I trial,newly diagnosed patients with m alignant gliomas with no prior external-beam therapy or chemotherapy were t reated with a single injection of I-131-labeled 81C6 through a Rickham rese rvoir into the resection cavity. The initial dose was 20 mCi and escalation wets in 20-mCi increments. Patients were observed for toxicity and respons e until death or for a minimum of 1 year after treatment. Results: We treated 42 patients with I-131-labeled 81C6 mAb in administered doses up to 180 mCi. Dose- limiting toxicity wets observed at doses greate r than 120 mCi and consisted of delayed neurotoxicity. None of the patients developed major hematologic toxicity. Median survival for patients with gl ioblastoma multiforme and for all patients was 69 and 79 weeks, respectivel y. Conclusion: The MTD for administration of I-131-labeled 81C6 into the SCRC of newly diagnosed patients with no prior radiation therapy or chemotherapy was 120 mCi. Dose-limiting toxicity was delayed neurologic toxicity. We ar e encouraged by the survival and toxicity and by the low 2.5% prevalence of debulking surgery for symptomatic radiation necrosis. (C) 2000 by American Society of Clinical Oncology.