Systemic therapy for patients with metastatic pheochromocytoma and paraganglioma

Pheochromocytomas and paragangliomas are rare neuroendocrine tumors derived from the paraganglia. These tumors frequently secrete excessive amounts of catecholamines leading to cardiovascular and gastrointestinal complications. While all pheochromocytomas and paragangliomas possess the potential for metastasis, actual metastatic occurrences are observed in approximately one third of cases. The metastases primarily affect the lymph nodes, skeletal system, liver, and lungs. Furthermore, patients often experience a reduced overall survival rate attributed to factors such as tumor size, disease advancement, and excessive catecholamine secretion. For several decades, treatment options for patients diagnosed with metastatic pheochromocytomas and paragangliomas have primarily included combination chemotherapy with cyclophosphamide, vincristine, and dacarbazine, along with Iodine-131-metaiodobenzylguanidine. However, significant advancements in scientific research over the past 25 years have enabled a comprehensive characterization of these tumors from biochemical, molecular, and diagnostic standpoints, resulting in the identification of new therapeutic alternatives for affected patients. In the last decade, we have witnessed the introduction of innovative systemic therapies specifically designed for those with metastatic pheochromocytomas and paragangliomas. In this review, we aim to present findings on the efficacy, safety, and overall activity from prospective clinical trials involving radiopharmaceuticals and tyrosine kinase inhibitors, and we will also outline the prospective advantages of additional novel therapies currently under evaluation.