Phase II Study of High-Dose [131I]Metaiodobenzylguanidine Therapy for Patients With Metastatic Pheochromocytoma and Paraganglioma

Purpose To evaluate the safety and efficacy of high-dose [I-131]metaiodobenzylguanidine ([I-131] MIBG) in the treatment of malignant pheochromocytoma (PHEO) and paraganglioma (PGL). Methods Fifty patients with metastatic PHEO or PGL, age 10 to 64 years, were treated with [I-131] MIBG doses ranging from 492 to 1,160 mCi (median, 12 mCi/kg). Cumulative [I-131] MIBG administered ranged from 492 to 3,191 mCi. Autologous hematopoietic stem cells were collected and cryopreserved before treatment with [I-131] MIBG greater than 12 mCi/kg or with a total dose greater than 500 mCi. Sixty-nine [I-131] MIBG infusions were given, which included infusions to 35 patients treated once and infusions to 15 patients who received two or three treatments. Response was evaluated by [I-123] MIBG scans, computed tomography/magnetic resonance imaging, urinary catecholamines/metanephrines, and chromogranin A. Results The overall complete response (CR) plus partial response (PR) rate in 49 evaluable patients was 22%. Additionally, 35% of patients achieved a CR or PR in at least one measure of response without progressive disease, and 8% of patients maintained stable disease for greater than 12 months. Thirty-five percent of patients experienced progressive disease within 1 year after therapy. The estimated 5-year overall survival rate was 64%. Toxicities included grades 3 to 4 neutropenia (87%) and thrombocytopenia (83%). Grades 3 to 4 nonhematologic toxicity included acute respiratory distress syndrome (n = 2), bronchiolitis obliterans organizing pneumonia (n = 2), pulmonary embolism (n = 1), fever with neutropenia (n = 7), acute hypertension (n = 10), infection (n = 2), myelodysplastic syndrome (n = 2), and hypogonadism (n = 4). Conclusion Although serious toxicity may occur, the survival and response rates achieved with high-dose [I-131] MIBG suggest its utility in the management of selected patients with metastatic PHEO and PGL.