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Pheochromocytoma and Paraganglioma Treatment (PDQ®)

Metastatic Pheochromocytoma Treatment

Standard treatment options for metastatic pheochromocytoma include the following:

  1. Surgery.
  2. Palliative therapy.

The most common sites of metastasis for pheochromocytoma or extra-adrenal paraganglioma are lymph nodes, bones, lungs, and liver. Patients with known or suspected malignancy should undergo staging with computed tomography or magnetic resonance imaging as well as functional imaging (e.g., with 123I-metaiodobenzylguanidine [MIBG]) to determine the extent and location of disease. Patients are often very symptomatic from excess catecholamine secretion. Phenoxybenzamine is effective, and metyrosine, which is a drug that blocks catecholamine synthesis, can be added if needed.

Surgery

If all identifiable disease is resectable, including a limited number of distant metastases, surgery can provide occasional long-term remission. If disease is unresectable, surgical debulking will not improve survival; however, it is occasionally indicated for symptom palliation.

Palliative Therapy

Chemotherapy

Chemotherapy has not been shown to improve survival in patients with metastatic pheochromocytoma; however, chemotherapy can be attempted for the palliation of symptoms.

The best-established chemotherapy regimen is a combination of cyclophosphamide, vincristine, and dacarbazine (the Averbuch protocol).[1] Results of this regimen in 18 patients after 22 years of follow-up demonstrated a complete response rate of 11%, a partial response rate of 44%, a biochemical response rate of 72%, and a median survival of 3.3 years.[2][Level of evidence: 3iiiDiv]

Several other chemotherapy regimens have been used in small numbers of patients, but the overall results were disappointing.[3,4]

Targeted therapy

Novel targeted therapies are emerging as potential treatment strategies for metastatic pheochromocytoma. Disappointing initial results were reported with the mammalian target of rapamycin (mTOR) inhibitor everolimus,[5] but results from a very small number of patients treated with the tyrosine kinase inhibitor sunitinib have been more promising.[6,7]

Radiation therapy

131I-MIBG radiation therapy has been used for the treatment of MIBG-avid metastases.[8,9] In a phase II study of high-dose 131I-MIBG radiation therapy involving 49 patients, 8% had a complete response, 14% had a partial response, and the estimated 5-year survival was 64%.[10][Level of evidence: 3iiiDiv] Approximately 60% of metastatic pheochromocytoma or paraganglioma sites are MIBG-avid;[10] protocol-based treatment with other experimental radiolabeled agents, such as radiolabeled somatostatin, can be considered for metastases that do not take up MIBG.

Other therapy

Other palliative treatment modalities include external-beam radiation therapy (e.g., for palliation of bone metastases) and embolization, radiofrequency ablation, or cryoablation (e.g., for palliation of bulky hepatic metastases or isolated bony metastases).

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with metastatic pheochromocytoma. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References

  1. Averbuch SD, Steakley CS, Young RC, et al.: Malignant pheochromocytoma: effective treatment with a combination of cyclophosphamide, vincristine, and dacarbazine. Ann Intern Med 109 (4): 267-73, 1988. [PUBMED Abstract]
  2. Huang H, Abraham J, Hung E, et al.: Treatment of malignant pheochromocytoma/paraganglioma with cyclophosphamide, vincristine, and dacarbazine: recommendation from a 22-year follow-up of 18 patients. Cancer 113 (8): 2020-8, 2008. [PUBMED Abstract]
  3. Nakane M, Takahashi S, Sekine I, et al.: Successful treatment of malignant pheochromocytoma with combination chemotherapy containing anthracycline. Ann Oncol 14 (9): 1449-51, 2003. [PUBMED Abstract]
  4. Kulke MH, Stuart K, Enzinger PC, et al.: Phase II study of temozolomide and thalidomide in patients with metastatic neuroendocrine tumors. J Clin Oncol 24 (3): 401-6, 2006. [PUBMED Abstract]
  5. Druce MR, Kaltsas GA, Fraenkel M, et al.: Novel and evolving therapies in the treatment of malignant phaeochromocytoma: experience with the mTOR inhibitor everolimus (RAD001). Horm Metab Res 41 (9): 697-702, 2009. [PUBMED Abstract]
  6. Jimenez C, Cabanillas ME, Santarpia L, et al.: Use of the tyrosine kinase inhibitor sunitinib in a patient with von Hippel-Lindau disease: targeting angiogenic factors in pheochromocytoma and other von Hippel-Lindau disease-related tumors. J Clin Endocrinol Metab 94 (2): 386-91, 2009. [PUBMED Abstract]
  7. Joshua AM, Ezzat S, Asa SL, et al.: Rationale and evidence for sunitinib in the treatment of malignant paraganglioma/pheochromocytoma. J Clin Endocrinol Metab 94 (1): 5-9, 2009. [PUBMED Abstract]
  8. Buscombe JR, Cwikla JB, Caplin ME, et al.: Long-term efficacy of low activity meta-[131I]iodobenzylguanidine therapy in patients with disseminated neuroendocrine tumours depends on initial response. Nucl Med Commun 26 (11): 969-76, 2005. [PUBMED Abstract]
  9. Scholz T, Eisenhofer G, Pacak K, et al.: Clinical review: Current treatment of malignant pheochromocytoma. J Clin Endocrinol Metab 92 (4): 1217-25, 2007. [PUBMED Abstract]
  10. Gonias S, Goldsby R, Matthay KK, et al.: Phase II study of high-dose [131I]metaiodobenzylguanidine therapy for patients with metastatic pheochromocytoma and paraganglioma. J Clin Oncol 27 (25): 4162-8, 2009. [PUBMED Abstract]
  • Updated: October 24, 2013