Phase II study of high-dose [131I]metaiodobenzylguanidine therapy for patients with metastatic pheochromocytoma and paraganglioma

Abstract

Purpose: To evaluate the safety and efficacy of high-dose [(131)I]metaiodobenzylguanidine ([(131)I]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 [(131)I]MIBG doses ranging from 492 to 1,160 mCi (median, 12 mCi/kg). Cumulative [(131)I]MIBG administered ranged from 492 to 3,191 mCi. Autologous hematopoietic stem cells were collected and cryopreserved before treatment with [(131)I]MIBG greater than 12 mCi/kg or with a total dose greater than 500 mCi. Sixty-nine [(131)I]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 [(123)I]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 [(131)I]MIBG suggest its utility in the management of selected patients with metastatic PHEO and PGL.

Conflict of interest statement

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

Figures

Fig 1.

Kaplan-Meier survival curves. (A) Overall and event-free survival for all patients enrolled on the study. (B) Overall survival according to prior chemotherapy. (C) Overall survival according to overall response. CR, complete response; PR, partial response; MR, minor response, SD, stable disease; PD, progressive disease.