INTRATHECAL I-131-LABELED ANTITENASCIN MONOCLONAL-ANTIBODY 81C6 TREATMENT OF PATIENTS WITH LEPTOMENINGEAL NEOPLASMS OR PRIMARY BRAIN-TUMOR RESECTION CAVITIES WITH SUBARACHNOID COMMUNICATION - PHASE-I TRIAL RESULTS

We aimed to determine the maximum tolerated dose (MTD) of I-131-labele d 81C6 in patients with leptomeningeal neoplasms or brain tumor resect ion cavities with subarachnoid communication and to identify any objec tive responses, 81C6 is a murine IgG monoclonal antibody that reacts w ith tenascin in gliomas/carcinomas but does not react with normal adul t brain. I-131-labeled 81C6 delivers intrathecal (IT) radiation to the se neoplasms, This study was a Phase I trial in which patients were tr eated with a single IT dose of I-131-labeled 81C6. Cohorts of three to six patients were treated with escalating doses of I-131 (starting do se, 40 mCi; 20 mCi escalations) on 10 mg 81C6, MTD is defined as the h ighest dose resulting in serious toxicity in no more than two of six p atients, Serious toxicity is defined as grade III/IV nonhematological toxicity or major hematological toxicity, We treated 31 patients (8 pe diatric and 23 adult), Eighteen had glioblastoma multiforme, Patients were treated with I-131 doses from 40 to 100 mCi, Hematological toxici ty was dose limiting and correlated with the administered I-131 dose, No grade III/IV nonhematological toxicities were encountered, A partia l response occurred in 1 patient and disease stabilization occurred in 13 (42%) of 31 patients. Twelve patients are alive (median follow-up, > 320 days); five are progression free > 409 days median posttreatmen t, The MTD of a single IT administration of I-131-labeled 81C6 in adul ts is 80 mCi I-131-labeled 81C6, The MTD in pediatric patients was not reached at I-131 doses up to 40 mCi normalized for body surface area.