Emerging Treatments for Advanced/Metastatic Pheochromocytoma and Paraganglioma

Curr Treat Options Oncol. 2020 Aug 29;21(11):85. doi: 10.1007/s11864-020-00787-z.


The incidence of metastatic pheochromocytoma (PHEO) and paraganglioma (PGL) may occur in as many as 35% of patients particularly with PGL and even more frequently in those with specific mutations. Biochemical, morphological, and molecular markers have been investigated for use in the distinction of benign from malignant PHEO/PGL. PHEO/PGL metastasizes via hematogenous or lymphatic routes and shows differences based on mutational status. The most common sites of involvement in patients that have an SDHB mutation are the bone (78%), lungs (45%), lymph nodes (36%), and liver (35%). In patients with sporadic PHEO/PGL, the most common sites of metastasis are the bones (64%), lungs (47%), lymph nodes (36%), and liver (32%). Metastases may be present at presentation or may occur later. Metastases to the liver and lungs are associated with a shorter survival. Overall, the estimated 5-year survival rates are between 34 and 74%. Currently, treatments for metastatic PHEO/PGL are essentially palliative. Surgery is potentially curative; however, tumor dissemination limits the chance for a curative resection. When surgical intervention is not amenable, the therapeutic options include radiolabeled MIBG (Azedra®-iobenguane 131 was recently FDA-approved for patients > 12 years and older with iobenguane scan positive) or systemic chemotherapy with cyclophosphamide, vincristine, and dacarbazine (CVD) with an overall objective response rate (ORR) of less than 40%; however, it is not clear if the administration of CVD impacts overall survival, as nearly all patients develop progressive and ultimately fatal disease. Other treatment modalities under investigation include cytoreductive techniques, novel radiopharmaceuticals, chemotherapy, radiotherapy, immunotherapy, and experimental therapies. Here we are discussing emerging treatment for advanced/metastatic PHEO/PGL.

Keywords: Genetics; Imaging; Oncogenic signaling; Paraganglioma; Pheochromocytoma; Therapy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • 3-Iodobenzylguanidine / therapeutic use
  • Adrenal Gland Neoplasms / pathology
  • Adrenal Gland Neoplasms / therapy*
  • Angiogenesis Inhibitors / therapeutic use
  • Antineoplastic Agents / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Bone Neoplasms / secondary
  • Bone Neoplasms / therapy
  • Cyclophosphamide / therapeutic use
  • Cytoreduction Surgical Procedures
  • Dacarbazine / therapeutic use
  • Everolimus / therapeutic use
  • Humans
  • Liver Neoplasms / secondary
  • Liver Neoplasms / therapy
  • Lung Neoplasms / secondary
  • Lung Neoplasms / therapy
  • Octreotide / analogs & derivatives
  • Octreotide / therapeutic use
  • Paraganglioma / pathology
  • Paraganglioma / secondary
  • Paraganglioma / therapy*
  • Pheochromocytoma / pathology
  • Pheochromocytoma / secondary
  • Pheochromocytoma / therapy*
  • Poly(ADP-ribose) Polymerase Inhibitors / therapeutic use
  • Radiopharmaceuticals / therapeutic use*
  • Surgical Procedures, Operative
  • Vincristine / therapeutic use


  • Angiogenesis Inhibitors
  • Antineoplastic Agents
  • Poly(ADP-ribose) Polymerase Inhibitors
  • Radiopharmaceuticals
  • 3-Iodobenzylguanidine
  • Vincristine
  • Dacarbazine
  • Cyclophosphamide
  • Everolimus
  • 90Y-octreotide, DOTA-Tyr(3)-
  • Octreotide

Supplementary concepts

  • CVD protocol