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Phase II Study on the Effect of Disease Sites, Age, and Prior Therapy on Response to Iodine-131-Metaiodobenzylguanidine Therapy in Refractory Neuroblastoma

Katherine K. Matthay, Gregory Yanik, Julia Messina, Alekist Quach, John Huberty, Su-Chun Cheng, Janet Veatch, Robert Goldsby, Patricia Brophy, Leslie S. Kersun, Randall A. Hawkins, John M. Maris

From the Departments of Pediatrics, Nuclear Medicine, and Biostatistics and Epidemiology, University of California at San Francisco and UCSF Children's Hospital, San Francisco, CA; Department of Pediatrics, University of Michigan and Mott Children's Hospital, Ann Arbor, MI; Department of Pediatrics, Children's Hospital of Philadelphia; University of Pennsylvania; and the Abramson Family Cancer Research Institute, Philadelphia, PA

Address reprint requests to Katherine K. Matthay, MD, Department of Pediatrics, University of California at San Francisco, 505 Parnassus, M647, San Francisco, CA 94143-0106; e-mail: matthayk{at}peds.ucsf.edu

Purpose: To evaluate the effect of disease sites and prior therapy on response and toxicity after iodine-131-metaiodobenzylguanidine (¹³¹I-MIBG) treatment of patients with resistant neuroblastoma.

Patients and Methods: One hundred sixty-four patients with progressive, refractory or relapsed high-risk neuroblastoma, age 2 to 30 years, were treated in a limited institution phase II study. Patients with cryopreserved hematopoietic stem cells (n = 148) were treated with 18 mCi/kg of ¹³¹I-MIBG. Those without hematopoietic stem cells (n = 16) received 12 mCi/kg. Patients were stratified according to prior myeloablative therapy and whether they had measurable soft tissue involvement or only bone and/or bone marrow disease.

Results: Hematologic toxicity was common, with 33% of patients receiving autologous hematopoietic stem cell support. Nonhematologic grade 3 or 4 toxicity was rare, with 5% of patients experiencing hepatic, 3.6% pulmonary, 10.9% infectious toxicity, and 9.7% with febrile neutropenia. The overall complete plus partial response rate was 36%. The response rate was significantly higher for patients with disease limited either to bone and bone marrow, or to soft tissue (compared with patients with both) for patients with fewer than three prior treatment regimens and for patients older than 12 years. The event-free survival (EFS) and overall survival (OS) times were significantly longer for patients achieving response, for those older than 12 years and with fewer than three prior treatment regimens. The OS was 49% at 1 year and 29% at 2 years; EFS was 18% at 1 year.

Conclusion: The high response rate and low nonhematologic toxicity with ¹³¹I-MIBG suggest incorporation of this agent into initial multimodal therapy of neuroblastoma.

Supported by the National Institute of Health Grants No. PO1 CA81403, 2MO1 RR0127, and M01-RR00240, as well by donations from the Campini Foundation, Conner Research Fund, Katie Dougherty Foundation, Kasle and Tkalcevik Neuroblastoma Research Fund, Thrasher Research Fund, Alex's Lemonade Stand Foundation, and the Evan T.J. Dunbar Neuroblastoma Foundation.

Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article.