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Originally published as JCO Early Release 10.1200/JCO.2007.15.7628 on January 26 2009 © 2009 American Society of Clinical Oncology.
Iodine-131—Metaiodobenzylguanidine Double Infusion With Autologous Stem-Cell Rescue for Neuroblastoma: A New Approaches to Neuroblastoma Therapy Phase I StudyFrom the Departments of Pediatrics and Radiology, Nuclear Medicine Program, University of California San Francisco and University of California San Francisco Children's Hospital, San Francisco; Departments of Radiology, Biostatistics, and Pediatrics, Keck School of Medicine, University of Southern California and Children's Hospital Los Angeles, Los Angeles, CA; Dana Farber Cancer Institute and Children's Hospital, Boston, MA; Department of Pediatrics, University of Michigan and Mott Children's Hospital, Ann Arbor, MI; and Department of Pediatrics, Children's Hospital of Philadelphia; University of Pennsylvania, Philadelphia, PA. Corresponding author: Katherine K. Matthay, MD, Department of Pediatrics, University of California, San Francisco, 505 Parnassus, M647, San Francisco, CA 94143-0106; e-mail: matthayk{at}peds.ucsf.edu. Purpose Iodine-131—metaiodobenzylguanidine (131I-MIBG) provides targeted radiotherapy with more than 30% response rate in refractory neuroblastoma, but 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 rescue (ASCR) 2 weeks after the second dose. Patients and Methods The 131I-MIBG dose was escalated using a 3 + 3 phase I trial design, with levels calculated by cumulative red marrow radiation index (RMI) from both infusions. Using 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 onto the study at levels 1 to 4, with 18 patients assessable for toxicity and 20 patients assessable for response. Cumulative 131I-MIBG given to achieve the target RMI ranged from 22 to 50 mCi/kg, with cumulative RMI of 3.2 to 8.92 Gy. No patient had a dose-limiting toxicity. Reversible grade 3 nonhematologic toxicity occurred in six patients at level 4, establishing the recommended cumulative dose as 36 mCi/kg. The median time to absolute neutrophil count more than 500/µL after ASCR was 13 days (4 to 27 days) and to platelet independence was 17 days (6 to 47 days). Responses included two partial responses, eight mixed responses, three stable disease, and seven progressive disease. Responses by semiquantitative MIBG score occurred in eight patients, soft tissue responses occurred in five of 11 patients, but bone marrow responses occurred in only two of 13 patients. Conclusion The lack of toxicity with this approach allowed dramatic dose intensification of 131I-MIBG, with minimal toxicity and promising activity. Supported in part by the National Institutes of Health Grants No. PO1 CA81403, R21 CA097758, CCSG CA82103, 2MO1 RR0127, M01-RR00240, as well by donations from the Campini Foundation, the Conner Research Fund, the Katie Dougherty Foundation, Kasle and Tkalcevik Neuroblastoma Research Fund, the Thrasher Research Fund, Alex's Lemonade Stand Foundation, the Evan T.J. Dunbar Neuroblastoma Foundation, Children's Neuroblastoma Cancer Foundation, Milken Family Foundation, and Pediatric Cancer Research Foundation. Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.
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Copyright © 2009 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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