Dosimetry, toxicity, and response in a phase IIa trial of no-carrier added iobenguane I-131 (nca-MIBG): A New Approach to Neuroblastoma Therapy (NANT) study

9512 Background: 131I-MIBG is specifically taken up in neuroblastoma, with a response rate >30% in relapsed disease. The presence of non-radioactive “carrier” MIBG molecules increases risk of cardiovascular side effects and can inhibit tumor uptake of 131I-MIBG, reducing tumor radiation. Our primary aim was to establish the maximum tolerated dose (MTD) of no-carrier-added MIBG with autologous hematopoietic stem cell (AHSC) support. Methods: Eligible patients were age 1-30 years with resistant neuroblastoma, MIBG avid tumors, and cryopreserved AHSC. The nca-MIBG therapeutic dose was escalated in 3 mCi/kg increments from 12-21 mCi/kg using a 3+3 design. The administered dose was limited by gamma image-derived pretreatment organ dosimetry and normal tissue tolerance estimates of Emami (1991). AHSC were infused 14 days post therapy. Response and toxicity were evaluated day 60. Dose limiting toxicity (DLT) was failure to engraft or grade 3 or 4 non-hematologic toxicity except grade 3 pre-defined exclusions. Re...