Purpose of This PDQ Summary
General Information
Cellular Classification
Stage Information
Treatment Option Overview
Localized Benign Pheochromocytoma

Current Clinical Trials

Regional Pheochromocytoma

Current Clinical Trials

Metastatic Pheochromocytoma

Current Clinical Trials

Recurrent Pheochromocytoma

Current Clinical Trials

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Changes to This Summary (01/03/2008)
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Purpose of This PDQ Summary

This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of pheochromocytoma. This summary is reviewed regularly and updated as necessary by the PDQ Adult Treatment Editorial Board.

Information about the following is included in this summary:

• Pathology.
• Signs and symptoms.
• Cellular classification.
• Staging.
• Treatment options by cancer stage.

This summary is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.

Some of the reference citations in the summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Adult Treatment Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations. Based on the strength of the available evidence, treatment options are described as either “standard” or “under clinical evaluation.” These classifications should not be used as a basis for reimbursement determinations.

This summary is available in a patient version, written in less technical language, and in Spanish.

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General Information

Pheochromocytoma is a rare tumor of chromaffin cells most commonly arising from the adrenal medulla. An estimated 800 cases are diagnosed yearly in the United States. The peak incidence is in the third to fifth decades of life. Bilateral disease is present in approximately 10% of patients. Bilaterality is much more common in familial pheochromocytoma and is often found in association with the familial multiple endocrine neoplasia syndromes (MEN, types 2A and 2B). In patients with MEN type 2 syndromes, the risk of developing a contralateral tumor following unilateral adrenalectomy is approximately 50%.[1] Other syndromes associated with pheochromocytoma include neurofibromatosis, von Hippel-Lindau disease, cerebellar hemangioblastoma, Sturge-Weber syndrome, and tuberous sclerosis. In a series of 82 unselected patients with pheochromocytoma, 23% were found to be carriers of associated familial disorders.[2] Therefore, all patients with pheochromocytomas should be screened for MEN2 and von Hippel-Lindau disease to avert further morbidity and mortality in the patients and their families. Extra-adrenal pheochromocytoma or functional paraganglioma occurs in approximately 10% to 15% of cases and may arise from any extra-adrenal chromaffin tissue in the body associated with sympathetic ganglia.

Extra-adrenal pheochromocytoma is most often located within the abdomen and may have greater malignant potential than adrenal pheochromocytoma.[3,4] Extra-adrenal tumors usually have a poorer prognosis than adrenal tumors.[3,4] In one series of 73 patients referred to tertiary care centers, however, no difference was found in the metastatic potential or the prognosis of extra-adrenal tumors compared to adrenal tumors.[5] Because of the production and release of catecholamines, pheochromocytomas cause hypertension. Only 0.1% to 0.5% of all hypertension patients, however, will be found to have a pheochromocytoma. The importance of the recognition of this disease is that more than 90% of patients properly diagnosed and treated are curable.[4,6-10]

The hypertension caused by pheochromocytoma may be sustained or paroxysmal and is often severe with occasional malignant features of encephalopathy, retinopathy, and proteinuria. Less commonly, severe hypertensive reactions may occur during incidental surgery, following trauma, exercise, or micturition (in the setting of bladder pheochromocytoma) when the diagnosis is unsuspected. Other clinical features of pheochromocytoma include headache, sweating, palpitation, tachycardia, and severe anxiety along with epigastric or chest pain. Orthostatic hypotension is frequently present and is probably caused by reduced intravascular volume following chronic adrenergic stimulation.

The diagnosis of pheochromocytoma is established by the demonstration of elevated 24-hour urinary excretion of free catecholamines (norepinephrine and epinephrine) or catecholamine metabolites (vanillylmandelic acid and total metanephrines). The measurement of plasma catecholamines can also be of value in the diagnosis of pheochromocytoma. The measurement of plasma catecholamines, however, has limited sensitivity and specificity. Plasma metanephrines have been reported to be more sensitive than plasma catecholamines. When 52 patients with pheochromocytoma were studied, every patient was found to have elevated plasma levels of metanephrines, but eight of the patients had normal levels of plasma catecholamines.[11] Pharmacologic testing with agents such as glucagon or clonidine is rarely required to make the diagnosis.[12,13]

Once the diagnosis is confirmed by biochemical determinations, the localization and extent of disease should be determined.[9] Ninety-seven percent of the tumors are found in the abdomen, 2% to 3% are found in the thorax, and 1% are found in the neck. The initial studies should be a chest film and abdominal computed tomographic (CT) scan. I¹³¹meta-iodobenzylguanidine (MIBG) has been found to be useful as a scintigraphic localization agent.[14,15] If the tumor is not adequately localized by these methods, then magnetic resonance imaging (MRI), or rarely, vena cava catheterization with selective venous sampling for catecholamines may be indicated.[16] CT and MRI scans are about equally sensitive (98% to 100%), while MIBG scanning has a sensitivity of only 80%. MIBG scanning, however, has a specificity of 100%, compared to a specificity of 70% for CT and MRI.[12] If extra-adrenal or metastatic disease is suspected, additional studies such as bone scan, liver-spleen scan, chest CT scan, or ultrasound may aid in determining the extent of disease.

Surgical resection is the standard curative modality.[17] If the primary tumor is localized to the adrenal gland and is benign, then survival is that of the normal age-matched population. In patients with unresectable, recurrent, or metastatic disease, long-term survival is possible; the overall 5-year survival, however, is less than 50%. Pharmacologic treatment of the catecholamine excess is mandatory and surgery, radiation therapy, or chemotherapy may provide palliative benefit.

References

1. Lairmore TC, Ball DW, Baylin SB, et al.: Management of pheochromocytomas in patients with multiple endocrine neoplasia type 2 syndromes. Ann Surg 217 (6): 595-601; discussion 601-3, 1993.  [PUBMED Abstract]
   
   
2. Neumann HP, Berger DP, Sigmund G, et al.: Pheochromocytomas, multiple endocrine neoplasia type 2, and von Hippel-Lindau disease. N Engl J Med 329 (21): 1531-8, 1993.  [PUBMED Abstract]
   
   
3. Sclafani LM, Woodruff JM, Brennan MF: Extraadrenal retroperitoneal paragangliomas: natural history and response to treatment. Surgery 108 (6): 1124-9; discussion 1129-30, 1990.  [PUBMED Abstract]
   
   
4. Whalen RK, Althausen AF, Daniels GH: Extra-adrenal pheochromocytoma. J Urol 147 (1): 1-10, 1992.  [PUBMED Abstract]
   
   
5. Pommier RF, Vetto JT, Billingsly K, et al.: Comparison of adrenal and extraadrenal pheochromocytomas. Surgery 114 (6): 1160-5; discussion 1165-6, 1993.  [PUBMED Abstract]
   
   
6. Manger WM, Gifford RW: Pheochromocytoma. New York: Springer-Verlag, 1977. 
   
   
7. Norton JA: Adrenal tumors. In: DeVita VT Jr, Hellman S, Rosenberg SA, eds.: Cancer: Principles and Practice of Oncology. 7th ed. Philadelphia, Pa: Lippincott Williams & Wilkins, 2005, pp 1528-39. 
   
   
8. Young JB, Landsberg L: Catecholamines and the adrenal medulla: pheochromocytoma. In: Wilson JD, Foster DW, Kronenberg HM, et al., eds.: Williams Textbook of Endocrinology. 9th ed. Philadelphia, Pa: W.B. Saunders Company, 1998, pp 705-716. 
   
   
9. Bravo EL, Gifford RW Jr: Current concepts. Pheochromocytoma: diagnosis, localization and management. N Engl J Med 311 (20): 1298-303, 1984.  [PUBMED Abstract]
   
   
10. Remine WH, Chong GC, Van Heerden JA, et al.: Current management of pheochromocytoma. Ann Surg 179 (5): 740-8, 1974.  [PUBMED Abstract]
    
    
11. Lenders JW, Keiser HR, Goldstein DS, et al.: Plasma metanephrines in the diagnosis of pheochromocytoma. Ann Intern Med 123 (2): 101-9, 1995.  [PUBMED Abstract]
    
    
12. Bravo EL: Evolving concepts in the pathophysiology, diagnosis, and treatment of pheochromocytoma. Endocr Rev 15 (3): 356-68, 1994.  [PUBMED Abstract]
    
    
13. Sjoberg RJ, Simcic KJ, Kidd GS: The clonidine suppression test for pheochromocytoma. A review of its utility and pitfalls. Arch Intern Med 152 (6): 1193-7, 1992.  [PUBMED Abstract]
    
    
14. McEwan AJ, Shapiro B, Sisson JC, et al.: Radio-iodobenzylguanidine for the scintigraphic location and therapy of adrenergic tumors. Semin Nucl Med 15 (2): 132-53, 1985.  [PUBMED Abstract]
    
    
15. Shapiro B, Copp JE, Sisson JC, et al.: Iodine-131 metaiodobenzylguanidine for the locating of suspected pheochromocytoma: experience in 400 cases. J Nucl Med 26 (6): 576-85, 1985.  [PUBMED Abstract]
    
    
16. Fink IJ, Reinig JW, Dwyer AJ, et al.: MR imaging of pheochromocytomas. J Comput Assist Tomogr 9 (3): 454-8, 1985 May-Jun.  [PUBMED Abstract]
    
    
17. Brennan MF, Keiser HR: Persistent and recurrent pheochromocytoma: the role of surgery. World J Surg 6 (4): 397-402, 1982.  [PUBMED Abstract]
    
    

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Cellular Classification

Histologically, pheochromocytoma is composed of large pleomorphic chromaffin cells. Electron microscopy reveals electron-dense neurosecretory granules. Approximately 10% of pheochromocytomas are considered to be malignant. No histologic features exist that distinguish benign from malignant tumors. Microscopic evidence for local invasion of tissue or blood vessels, however, suggests malignancy.[1] Criteria based on tumor size, mitotic index, and DNA ploidy have been reported to be helpful in some series, though they are not always reliable predictors of biologic behavior.[2-4] Because the distinction between benign and malignant tumors cannot be made with certainty, careful surveillance is needed for a prolonged period after the initial surgical resection.

References

1. Manger WM, Gifford RW: Pheochromocytoma. New York: Springer-Verlag, 1977. 
   
   
2. Amberson JB, Vaughan ED Jr, Gray GF, et al.: Flow cytometric determination of nuclear DNA content in benign adrenal pheochromocytomas. Urology 30 (2): 102-4, 1987.  [PUBMED Abstract]
   
   
3. Hosaka Y, Rainwater LM, Grant CS, et al.: Pheochromocytoma: nuclear deoxyribonucleic acid patterns studied by flow cytometry. Surgery 100 (6): 1003-10, 1986.  [PUBMED Abstract]
   
   
4. Capella C, Riva C, Cornaggia M, et al.: Histopathology, cytology and cytochemistry of pheochromocytomas and paragangliomas including chemodectomas. Pathol Res Pract 183 (2): 176-87, 1988.  [PUBMED Abstract]
   
   

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Stage Information

There is no accepted staging system for pheochromocytoma.

Localized benign

Data suggest that for patients with resectable, benign pheochromocytoma, the overall survival is equal to that of the age-matched normal population.[1,2]

Regional

No information is available at this time.

Metastatic

Data from several series suggest that the 5-year survival rate for patients with metastatic, malignant pheochromocytoma is approximately 40%.[1-3] In three retrospective studies of patients with either metastatic or recurrent pheochromocytoma, the 5-year survival ranged from 32% to 60%.[4]

References

1. Douglass EC, Shapiro DN, Valentine M, et al.: Alveolar rhabdomyosarcoma with the t(2;13): cytogenetic findings and clinicopathologic correlations. Med Pediatr Oncol 21 (2): 83-7, 1993.  [PUBMED Abstract]
   
   
2. Remine WH, Chong GC, Van Heerden JA, et al.: Current management of pheochromocytoma. Ann Surg 179 (5): 740-8, 1974.  [PUBMED Abstract]
   
   
3. van Heerden JA, Sheps SG, Hamberger B, et al.: Pheochromocytoma: current status and changing trends. Surgery 91 (4): 367-73, 1982.  [PUBMED Abstract]
   
   
4. Kvols LK, Perry RR, Vinik AI, et al.: Neoplasms of the neuroendocrine system and neoplasms of the gastroenteropancreatic endocrine system. In: Holland JC, Frei E, eds.: Cancer Medicine e.5. 5th ed. Hamilton, Ontario: B.C. Decker Inc, 2000, pp 1121-1172. 
   
   

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Treatment Option Overview

Following the diagnosis of pheochromocytoma, medical management should be initiated with phenoxybenzamine (or alpha-1 adrenergic receptor antagonists, such as prazosin) to block alpha-adrenergic activity. Diuretics should not be used, and re-expansion of plasma volume may be accomplished by liberal salt or fluid intake. Low doses of a beta blocker such as propranolol are useful adjuncts to control blood pressure and cardiac tachyarrhythmias, but only after alpha blockade is established. Labetalol, an alpha- and beta-adrenergic blocker, has also been shown to be effective in the control of blood pressure and symptoms of pheochromocytoma. The use of combined alpha- and beta-adrenergic blockers or calcium antagonists can be continued on a long-term basis when the tumor is unresectable. For more refractory cases, or when severe and prolonged hypertension results from malignant disease, alpha-methyl-para-tyrosine is effective by inhibiting catecholamine synthesis.[1-3] This drug can decrease circulating catecholamines by 80% and alleviate many disease-related symptoms.[1-4]

References

1. Manger WM, Gifford RW: Pheochromocytoma. New York: Springer-Verlag, 1977. 
   
   
2. Young JB, Landsberg L: Catecholamines and the adrenal medulla: pheochromocytoma. In: Wilson JD, Foster DW, Kronenberg HM, et al., eds.: Williams Textbook of Endocrinology. 9th ed. Philadelphia, Pa: W.B. Saunders Company, 1998, pp 705-716. 
   
   
3. Bravo EL, Gifford RW Jr: Current concepts. Pheochromocytoma: diagnosis, localization and management. N Engl J Med 311 (20): 1298-303, 1984.  [PUBMED Abstract]
   
   
4. Bravo EL: Evolving concepts in the pathophysiology, diagnosis, and treatment of pheochromocytoma. Endocr Rev 15 (3): 356-68, 1994.  [PUBMED Abstract]
   
   

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Localized Benign Pheochromocytoma

Standard treatment options:

For localized pheochromocytoma confined to one or both adrenal glands, adequate treatment is complete surgical resection consisting of total adrenalectomy. Although patients with an associated MEN type 2 syndrome are at risk for bilateral tumors, the use of prophylactic contralateral adrenalectomy is not recommended for patients with unilateral tumors.[1] Preoperative medical management of the effect of excessive adrenergic stimulation is necessary. Intraoperatively, blood pressure is controlled by titration of small doses of phentolamine or nitroprusside, and cardiac arrhythmias may be treated with propranolol or lidocaine. Postoperatively, hypotension is common and should be treated with volume expansion (often large volumes are required). Postoperative hypertension is best treated with diuretics. The standard anterior approach to the adrenal gland is used, and the entire gland is removed; simple tumor excision should not be attempted. The abdomen and retroperitoneum are examined thoroughly for the presence of extra-adrenal disease. After one week or more following surgery, repeated biochemical assays for catecholamines and/or metabolites are performed to confirm that all functioning pheochromocytoma has been removed. In experienced hands, the operative mortality is less than 2% to 3% and the end result of complete surgical resection of benign pheochromocytoma is a normal life expectancy.[2-4]

Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with localized benign 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. Lairmore TC, Ball DW, Baylin SB, et al.: Management of pheochromocytomas in patients with multiple endocrine neoplasia type 2 syndromes. Ann Surg 217 (6): 595-601; discussion 601-3, 1993.  [PUBMED Abstract]
   
   
2. Norton JA: Adrenal tumors. In: DeVita VT Jr, Hellman S, Rosenberg SA, eds.: Cancer: Principles and Practice of Oncology. 7th ed. Philadelphia, Pa: Lippincott Williams & Wilkins, 2005, pp 1528-39. 
   
   
3. Young JB, Landsberg L: Catecholamines and the adrenal medulla: pheochromocytoma. In: Wilson JD, Foster DW, Kronenberg HM, et al., eds.: Williams Textbook of Endocrinology. 9th ed. Philadelphia, Pa: W.B. Saunders Company, 1998, pp 705-716. 
   
   
4. Bravo EL, Gifford RW Jr: Current concepts. Pheochromocytoma: diagnosis, localization and management. N Engl J Med 311 (20): 1298-303, 1984.  [PUBMED Abstract]
   
   

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Regional Pheochromocytoma

Standard treatment options: [1-6]

Pheochromocytoma with regional lymphatic metastasis or local extension should be treated by aggressive surgical resection with an attempt to remove all gross evidence of disease. If this is accomplished, and confirmed by biochemical determinations, long-term survival may be achieved. These patients, however, will require careful monitoring indefinitely for recurrent disease. If regional disease remains, the hypertension and symptoms caused by catecholamine excess should be treated by adrenergic blockade and catecholamine synthesis inhibition as necessary.

Radiation therapy or combination chemotherapy may be palliative for symptoms or morbidity resulting from local invasion by tumor. Treatment with targeted radiation therapy using I¹³¹ meta-iodobenzylguanidine (I¹³¹ MIBG) has met with limited success. In approximately 35% of the patients screened, the tumor has sufficient uptake of the radioisotope to allow for a therapeutic dose.[7,8] In a group of 28 patients shown to have sufficient uptake of I¹³¹ MIBG, objective partial responses were observed in 29% of the patients, and biochemical improvement was noted in 43% of the patients.[9]

Several single agents and drug combinations have been evaluated in a limited number of patients with variable results.[7] The most active chemotherapy regimen appears to be the combination of cyclophosphamide, vincristine, and dacarbazine (CVD).[10] CVD has been shown to produce partial remissions of moderate duration in symptomatic patients. Analysis of 23 patients treated with CVD showed 61% of the patients had objective evidence of tumor regression, and 74% of the patients had evidence of biochemical response. In addition, improved control of hypertension, reduced need for antihypertensive medications, and improvement in overall performance status was observed. Since hypertensive episodes have been reported following chemotherapy, patients need to be prepared with adrenergic blockers prior to treatment. No evidence exists that chemotherapy contributes to improved patient survival. Chemotherapy should be used only for palliation in symptomatic patients.[7,11]

Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with regional 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. Manger WM, Gifford RW: Pheochromocytoma. New York: Springer-Verlag, 1977. 
   
   
2. Norton JA: Adrenal tumors. In: DeVita VT Jr, Hellman S, Rosenberg SA, eds.: Cancer: Principles and Practice of Oncology. 7th ed. Philadelphia, Pa: Lippincott Williams & Wilkins, 2005, pp 1528-39. 
   
   
3. Young JB, Landsberg L: Catecholamines and the adrenal medulla: pheochromocytoma. In: Wilson JD, Foster DW, Kronenberg HM, et al., eds.: Williams Textbook of Endocrinology. 9th ed. Philadelphia, Pa: W.B. Saunders Company, 1998, pp 705-716. 
   
   
4. Remine WH, Chong GC, Van Heerden JA, et al.: Current management of pheochromocytoma. Ann Surg 179 (5): 740-8, 1974.  [PUBMED Abstract]
   
   
5. McEwan AJ, Shapiro B, Sisson JC, et al.: Radio-iodobenzylguanidine for the scintigraphic location and therapy of adrenergic tumors. Semin Nucl Med 15 (2): 132-53, 1985.  [PUBMED Abstract]
   
   
6. Drasin H: Treatment of malignant pheochromocytoma. West J Med 128 (2): 106-11, 1978.  [PUBMED Abstract]
   
   
7. Kvols LK, Perry RR, Vinik AI, et al.: Neoplasms of the neuroendocrine system and neoplasms of the gastroenteropancreatic endocrine system. In: Holland JC, Frei E, eds.: Cancer Medicine e.5. 5th ed. Hamilton, Ontario: B.C. Decker Inc, 2000, pp 1121-1172. 
   
   
8. Shapiro B, Fig LM: Management of pheochromocytoma. Endocrinol Metab Clin North Am 18 (2): 443-81, 1989.  [PUBMED Abstract]
   
   
9. Shapiro B, Sisson JC, Wieland DM, et al.: Radiopharmaceutical therapy of malignant pheochromocytoma with [131I]metaiodobenzylguanidine: results from ten years of experience. J Nucl Biol Med 35 (4): 269-76, 1991 Oct-Dec.  [PUBMED Abstract]
   
   
10. 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]
    
    
11. Brennan MF, Keiser HR: Persistent and recurrent pheochromocytoma: the role of surgery. World J Surg 6 (4): 397-402, 1982.  [PUBMED Abstract]
    
    

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Metastatic Pheochromocytoma

Standard treatment options:

Sites of metastatic disease most commonly observed include lymph nodes, bones, liver, and lungs. Liver involvement may be the result of direct extension from right-sided primary tumors. Biochemical confirmation of recurrence and localization of metastatic lesions with I¹³¹ meta-iodobenzylguanidine (I¹³¹ MIBG) scans can confirm the presence of metastasis. Aggressive surgical resection of accessible recurrent disease or metastases that will render the patient free of gross disease with the potential for normal biochemical determinations should be attempted. If successful, long-term survival may be achieved; however, careful monitoring for recurrent disease will be necessary indefinitely.[1,2]

No evidence exists that partial surgical debulking of tumor results in improved survival or reduction in symptoms. Surgical intervention or radiation therapy may be indicated for palliation of local complications due to metastatic disease. Long-term medical management of symptoms using adrenergic blockade and catecholamine synthesis inhibition is indicated and will prevent catastrophic complications from chronic and extreme catecholamine excess.[3,4]

Several single agents and drug combinations have been used in a limited number of patients with variable results.[5,6] The most active chemotherapy regimen appears to be the combination of cyclophosphamide, vincristine, and dacarbazine (CVD).[7] CVD has been shown to produce partial remissions of moderate duration in symptomatic patients. Analysis of 23 patients treated with CVD showed that 61% of the patients had objective evidence of tumor regression, and 74% of the patients had evidence of biochemical response. In addition, improved control of hypertension, reduced need for antihypertensive medications, and improvement in overall performance status was observed. Since hypertensive episodes have been reported following chemotherapy, patients need to be prepared with adrenergic blockers prior to treatment. No evidence exists that chemotherapy prolongs the survival of patients with metastatic disease. Chemotherapy should be used only for palliation in symptomatic patients.[5,7]

External radiation therapy can achieve palliation of painful bone metastases.

Treatment with targeted radiation therapy using I¹³¹ MIBG has met with limited success. In approximately 35% of patients screened, the tumor has sufficient uptake of the radioisotope to allow for a therapeutic dose.[5,8] Of 28 patients who were shown to have sufficient uptake of I¹³¹ MIBG, objective partial responses were observed in 29% of the patients, and biochemical improvement was noted in 43% of the patients.[9]

Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry 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. Drasin H: Treatment of malignant pheochromocytoma. West J Med 128 (2): 106-11, 1978.  [PUBMED Abstract]
   
   
2. Brennan MF, Keiser HR: Persistent and recurrent pheochromocytoma: the role of surgery. World J Surg 6 (4): 397-402, 1982.  [PUBMED Abstract]
   
   
3. Young JB, Landsberg L: Catecholamines and the adrenal medulla: pheochromocytoma. In: Wilson JD, Foster DW, Kronenberg HM, et al., eds.: Williams Textbook of Endocrinology. 9th ed. Philadelphia, Pa: W.B. Saunders Company, 1998, pp 705-716. 
   
   
4. Bravo EL, Gifford RW Jr: Current concepts. Pheochromocytoma: diagnosis, localization and management. N Engl J Med 311 (20): 1298-303, 1984.  [PUBMED Abstract]
   
   
5. Kvols LK, Perry RR, Vinik AI, et al.: Neoplasms of the neuroendocrine system and neoplasms of the gastroenteropancreatic endocrine system. In: Holland JC, Frei E, eds.: Cancer Medicine e.5. 5th ed. Hamilton, Ontario: B.C. Decker Inc, 2000, pp 1121-1172. 
   
   
6. Schlumberger M, Gicquel C, Lumbroso J, et al.: Malignant pheochromocytoma: clinical, biological, histologic and therapeutic data in a series of 20 patients with distant metastases. J Endocrinol Invest 15 (9): 631-42, 1992.  [PUBMED Abstract]
   
   
7. 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]
   
   
8. Shapiro B, Fig LM: Management of pheochromocytoma. Endocrinol Metab Clin North Am 18 (2): 443-81, 1989.  [PUBMED Abstract]
   
   
9. Shapiro B, Sisson JC, Wieland DM, et al.: Radiopharmaceutical therapy of malignant pheochromocytoma with [131I]metaiodobenzylguanidine: results from ten years of experience. J Nucl Biol Med 35 (4): 269-76, 1991 Oct-Dec.  [PUBMED Abstract]
   
   

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Recurrent Pheochromocytoma

Standard treatment options:

To detect recurrent tumor, asymptomatic patients should undergo frequent clinical and biochemical assessments following their initial surgical resection. The median time for recurrence of malignant pheochromocytoma following initial resection is approximately 6 years and may be as long as 20 years. The natural history of recurrent pheochromocytoma is variable. Some patients experience an indolent course following recurrence with or without additional treatment. Review of clinical series of patients with recurrent pheochromocytoma shows that 5-year survival rates are 32% to 60%.[1] Most patients, however, develop morbidity from the local and biochemical effects of recurrent tumor and will require palliative treatment.

Aggressive surgical resection of accessible recurrent disease or metastases that will render the patient free of gross disease with the potential for normal biochemical determinations should be attempted. If successful, long-term survival may be achieved, however, careful monitoring for other sites of recurrent disease will be necessary indefinitely.[2-4] Surgical debulking of malignant tumor that cannot be completely excised carries an operative risk without proven benefit and is generally not recommended.[5] Surgery or radiation therapy, however, may be indicated for palliation of local complications due to recurrent disease. Long-term medical management of symptoms using adrenergic blockade and catecholamine synthesis inhibition is indicated and will prevent catastrophic complications from chronic and extreme catecholamine excess.[6-8]

External radiation therapy can achieve palliation of painful bone metastases. Treatment with targeted radiation therapy using I¹³¹ meta-iodobenzylguanidine (I¹³¹ MIBG) has met with limited success. In approximately 35% of patients screened, the tumor has sufficient uptake of the radioisotope to allow for a therapeutic dose.[1,5] In a group of 28 patients shown to have sufficient uptake of I¹³¹ MIBG, objective partial responses were observed in 29% of the patients, and biochemical improvement was noted in 43% of the patients.[9]

Several single agents and drug combinations have been evaluated in a limited number of patients with variable results.[1] The most active chemotherapy regimen appears to be the combination of cyclophosphamide, vincristine, and dacarbazine (CVD).[10] CVD has been shown to produce partial remissions of moderate duration in symptomatic patients. Analysis of 23 patients treated with CVD showed that 61% of the patients had objective evidence of tumor regression, and 74% of the patients had evidence of biochemical response. In addition, improved control of hypertension, reduced need for antihypertensive medications, and improvement in overall performance status was observed. Since hypertensive episodes have been reported following chemotherapy, patients need to be prepared with adrenergic blockers. No evidence exists that chemotherapy contributes to improved patient survival. Chemotherapy should be used only for palliation in symptomatic patients.[1,10]

Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with recurrent 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. Kvols LK, Perry RR, Vinik AI, et al.: Neoplasms of the neuroendocrine system and neoplasms of the gastroenteropancreatic endocrine system. In: Holland JC, Frei E, eds.: Cancer Medicine e.5. 5th ed. Hamilton, Ontario: B.C. Decker Inc, 2000, pp 1121-1172. 
   
   
2. Remine WH, Chong GC, Van Heerden JA, et al.: Current management of pheochromocytoma. Ann Surg 179 (5): 740-8, 1974.  [PUBMED Abstract]
   
   
3. Drasin H: Treatment of malignant pheochromocytoma. West J Med 128 (2): 106-11, 1978.  [PUBMED Abstract]
   
   
4. Brennan MF, Keiser HR: Persistent and recurrent pheochromocytoma: the role of surgery. World J Surg 6 (4): 397-402, 1982.  [PUBMED Abstract]
   
   
5. Shapiro B, Fig LM: Management of pheochromocytoma. Endocrinol Metab Clin North Am 18 (2): 443-81, 1989.  [PUBMED Abstract]
   
   
6. Manger WM, Gifford RW: Pheochromocytoma. New York: Springer-Verlag, 1977. 
   
   
7. Young JB, Landsberg L: Catecholamines and the adrenal medulla: pheochromocytoma. In: Wilson JD, Foster DW, Kronenberg HM, et al., eds.: Williams Textbook of Endocrinology. 9th ed. Philadelphia, Pa: W.B. Saunders Company, 1998, pp 705-716. 
   
   
8. Bravo EL, Gifford RW Jr: Current concepts. Pheochromocytoma: diagnosis, localization and management. N Engl J Med 311 (20): 1298-303, 1984.  [PUBMED Abstract]
   
   
9. Shapiro B, Sisson JC, Wieland DM, et al.: Radiopharmaceutical therapy of malignant pheochromocytoma with [131I]metaiodobenzylguanidine: results from ten years of experience. J Nucl Biol Med 35 (4): 269-76, 1991 Oct-Dec.  [PUBMED Abstract]
   
   
10. 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]
    
    

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For more information, U.S. residents may call the National Cancer Institute's (NCI's) Cancer Information Service toll-free at 1-800-4-CANCER (1-800-422-6237) Monday through Friday from 9:00 a.m. to 4:30 p.m. Deaf and hard-of-hearing callers with TTY equipment may call 1-800-332-8615. The call is free and a trained Cancer Information Specialist is available to answer your questions.

Chat online

The NCI's LiveHelp® online chat service provides Internet users with the ability to chat online with an Information Specialist. The service is available from 9:00 a.m. to 11:00 p.m. Eastern time, Monday through Friday. Information Specialists can help Internet users find information on NCI Web sites and answer questions about cancer.

Write to us

For more information from the NCI, please write to this address:

NCI Public Inquiries Office

Suite 3036A

6116 Executive Boulevard, MSC8322

Bethesda, MD 20892-8322

Search the NCI Web site

The NCI Web site provides online access to information on cancer, clinical trials, and other Web sites and organizations that offer support and resources for cancer patients and their families. For a quick search, use our “Best Bets” search box in the upper right hand corner of each Web page. The results that are most closely related to your search term will be listed as Best Bets at the top of the list of search results.

There are also many other places to get materials and information about cancer treatment and services. Hospitals in your area may have information about local and regional agencies that have information on finances, getting to and from treatment, receiving care at home, and dealing with problems related to cancer treatment.

Find Publications

The NCI has booklets and other materials for patients, health professionals, and the public. These publications discuss types of cancer, methods of cancer treatment, coping with cancer, and clinical trials. Some publications provide information on tests for cancer, cancer causes and prevention, cancer statistics, and NCI research activities. NCI materials on these and other topics may be ordered online or printed directly from the NCI Publications Locator. These materials can also be ordered by telephone from the Cancer Information Service toll-free at 1-800-4-CANCER (1-800-422-6237), TTY at 1-800-332-8615.

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Changes to This Summary (01/03/2008)

The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.

Added Purpose of This PDQ Summary as a section.

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More Information

About PDQ

• PDQ® - NCI's Comprehensive Cancer Database.

  Full description of the NCI PDQ database.

Additional PDQ Summaries

• PDQ® Cancer Information Summaries: Adult Treatment

  Treatment options for adult cancers.

• PDQ® Cancer Information Summaries: Pediatric Treatment

  Treatment options for childhood cancers.

• PDQ® Cancer Information Summaries: Supportive and Palliative Care

  Side effects of cancer treatment, management of cancer-related complications and pain, and psychosocial concerns.

• PDQ® Cancer Information Summaries: Screening/Detection (Testing for Cancer)

  Tests or procedures that detect specific types of cancer.

• PDQ® Cancer Information Summaries: Prevention

  Risk factors and methods to increase chances of preventing specific types of cancer.

• PDQ® Cancer Information Summaries: Genetics

  Genetics of specific cancers and inherited cancer syndromes, and ethical, legal, and social concerns.

• PDQ® Cancer Information Summaries: Complementary and Alternative Medicine

  Information about complementary and alternative forms of treatment for patients with cancer.

Important:

This information is intended mainly for use by doctors and other health care professionals. If you have questions about this topic, you can ask your doctor, or call the Cancer Information Service at 1-800-4-CANCER (1-800-422-6237).

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