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9513 Background: 131I-metaiodobenzylguanidine (MIBG) is a targeted radiopharmaceutical with activity in neuroblastoma. Irinotecan is a radiosensitizer with activity in neuroblastoma. This phase I s...

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...

9532 Background: TrkB acts as an oncogenic kinase in a subset of human NB. Lestaurtinib, a multi-kinase inhibitor with potent activity against Trk kinases, has demonstrated anti-tumor activity in p...

9011 Background: 131I-MIBG provides targeted radiotherapy with >30% response in refractory neuroblastoma, but the activity infused is limited by radiation safety and hematologic toxicity. The goal was to determine the maximum tolerated dose of 131I-MIBG in two consecutive infusions at a 2-week interval, supported by autologous stem cell transplant (ASCT) 2 weeks after the second dose. Methods: The 131I-MIBG was escalated in a 3+3 Phase I trial design, with levels calculated by total red marrow radiation index (RMI) from the double infusion. The first infusion of 131I-MIBG was 12, 15, 18 and 21 mCi/kg for levels 1, 2, 3 and 4 respectively. Using detailed dosimetry, the second infusion was adjusted to achieve the target RMI, except at Level 4, where the second infusion was capped at 21 mCi/kg. Results: Twenty-one patients were enrolled at Level 1–4, with 18 evaluable for toxicity. Median age at enrollment was 7 years, all were heavily pretreated, including 12 with prior high dose therapy and ASCT, and 12 patients had bone marrow tumor. Cumulative 131I-MIBG given to achieve the target RMI ranged from 18 mci/kg to 49 mCi/kg. RMI delivered per mCi of MIBG decreased in 15/19 patients by mean of 0.21 cGy/mCi with the second infusion. Hematologic toxicity was acceptable, with median time to ANC>500 after ASCT of 13 (4–27) days. Platelet transfusion was required in 15/18 patients, with median time to platelet independence of 18 (6–47) days after ASCT. There were no non-hematologic toxicities above grade 2 attributed to therapy, though 9 patients had grade 1–2 elevations of transaminase, and 1 had grade 2 hypothyroidism. Responses in 17 evaluable patients included 1 PR, 4 MR, 6 SD, and 6 PD. Eleven patients are alive at median of 361 days (46–483); 5 died of PD and 1 of unrelated toxicity. Conclusion: The lack of toxicity with this approach allowed dramatic dose intensification of 131I-MIBG, with minimal toxicity and the possibility of improved response. [Table: see text] No significant financial relationships to disclose.

8505 Background: To determine the maximum tolerated dose (MTD) and toxicity of 131I-MIBG with CEM (carboplatin, etoposide, melphalan) and autologous transplant (AT). Methods: 24 children age 1.5–16...

8504 Purpose: To evaluate the effect of disease sites, prior therapy and dose on response rates and toxicity with 131I-MIBG treatment of children with refractory neuroblastoma. Methods: 151 patient...