New Directions in Treatment of Metastatic or Advanced Pheochromocytomas and Sympathetic Paragangliomas: an American, Contemporary, Pragmatic Approach

Multiple therapies with novel mechanisms have been explored in clinical trials for the treatment of metastatic pheochromocytomas and paragangliomas. We review current and future therapies for this disease and provide guidance on how and when to prescribe them based on tumor progression, clinical manifestations, molecular features, and social factors.Approximately 60-70% of metastatic pheochromocytomas and paragangliomas express the noradrenaline transporter in their cell membranes. High specific activity iodine-131 metaiodobenzylguanidine has been recently approved by the US Food and Drug Administration for the treatment of metastatic pheochromocytomas and paragangliomas that express the noradrenaline transporter, in patients aged ≥ 12 years. More than 90% of patients treated with this medication exhibit clinical benefits. However, other therapies with novel mechanisms of action are needed to help all patients with this disease. Treatment of metastatic pheochromocytomas and paragangliomas is recommended based on the severity of symptoms, the progression of the disease, and the patient's performance status. Currently available therapies include surgery; systemic chemotherapy with cyclophosphamide, vincristine, and dacarbazine, or with temozolomide; high specific activity iodine-131 metaiodobenzylguanidine; peptide receptor radionuclide therapy; immunotherapy; tyrosine kinase inhibitors; and hypoxia-inducible factor 2 alpha inhibitors. Financial and social factors such as health insurance coverage and disparities also impact current clinical practice in the USA.