Table of Contents Purpose of This PDQ Summary General Information Cellular Classification Stage Information Treatment Option Overview Localized Benign Pheochromocytoma
Regional Pheochromocytoma Metastatic Pheochromocytoma Recurrent Pheochromocytoma Get More Information From NCI Changes to This Summary (01/03/2008) More Information
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 1.
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 2 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 3, written in less technical language, and in Spanish 4. 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
-
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]
-
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]
-
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]
-
Whalen RK, Althausen AF, Daniels GH: Extra-adrenal pheochromocytoma. J Urol 147 (1): 1-10, 1992.
[PUBMED Abstract]
-
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]
-
Manger WM, Gifford RW: Pheochromocytoma. New York: Springer-Verlag, 1977.
-
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.
-
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.
-
Bravo EL, Gifford RW Jr: Current concepts. Pheochromocytoma: diagnosis, localization and management. N Engl J Med 311 (20): 1298-303, 1984.
[PUBMED Abstract]
-
Remine WH, Chong GC, Van Heerden JA, et al.: Current management of pheochromocytoma. Ann Surg 179 (5): 740-8, 1974.
[PUBMED Abstract]
-
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]
-
Bravo EL: Evolving concepts in the pathophysiology, diagnosis, and treatment of pheochromocytoma. Endocr Rev 15 (3): 356-68, 1994.
[PUBMED Abstract]
-
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]
-
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]
-
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]
-
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]
-
Brennan MF, Keiser HR: Persistent and recurrent pheochromocytoma: the role of surgery. World J Surg 6 (4): 397-402, 1982.
[PUBMED Abstract]
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
-
Manger WM, Gifford RW: Pheochromocytoma. New York: Springer-Verlag, 1977.
-
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]
-
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]
-
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]
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
-
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]
-
Remine WH, Chong GC, Van Heerden JA, et al.: Current management of pheochromocytoma. Ann Surg 179 (5): 740-8, 1974.
[PUBMED Abstract]
-
van Heerden JA, Sheps SG, Hamberger B, et al.: Pheochromocytoma: current status and changing trends. Surgery 91 (4): 367-73, 1982.
[PUBMED Abstract]
-
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.
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
-
Manger WM, Gifford RW: Pheochromocytoma. New York: Springer-Verlag, 1977.
-
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.
-
Bravo EL, Gifford RW Jr: Current concepts. Pheochromocytoma: diagnosis, localization and management. N Engl J Med 311 (20): 1298-303, 1984.
[PUBMED Abstract]
-
Bravo EL: Evolving concepts in the pathophysiology, diagnosis, and treatment of pheochromocytoma. Endocr Rev 15 (3): 356-68, 1994.
[PUBMED Abstract]
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]
Current Clinical Trials
Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with localized benign pheochromocytoma 5. 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 6.
References
-
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]
-
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.
-
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.
-
Bravo EL, Gifford RW Jr: Current concepts. Pheochromocytoma: diagnosis, localization and management. N Engl J Med 311 (20): 1298-303, 1984.
[PUBMED Abstract]
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]
Current Clinical Trials
Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with regional pheochromocytoma 7. 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 6.
References
-
Manger WM, Gifford RW: Pheochromocytoma. New York: Springer-Verlag, 1977.
-
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.
-
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.
-
Remine WH, Chong GC, Van Heerden JA, et al.: Current management of pheochromocytoma. Ann Surg 179 (5): 740-8, 1974.
[PUBMED Abstract]
-
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]
-
Drasin H: Treatment of malignant pheochromocytoma. West J Med 128 (2): 106-11, 1978.
[PUBMED Abstract]
-
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.
-
Shapiro B, Fig LM: Management of pheochromocytoma. Endocrinol Metab Clin North Am 18 (2): 443-81, 1989.
[PUBMED Abstract]
-
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]
-
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]
-
Brennan MF, Keiser HR: Persistent and recurrent pheochromocytoma: the role of surgery. World J Surg 6 (4): 397-402, 1982.
[PUBMED Abstract]
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]
Current Clinical Trials
Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with metastatic pheochromocytoma 8. 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 6.
References
-
Drasin H: Treatment of malignant pheochromocytoma. West J Med 128 (2): 106-11, 1978.
[PUBMED Abstract]
-
Brennan MF, Keiser HR: Persistent and recurrent pheochromocytoma: the role of surgery. World J Surg 6 (4): 397-402, 1982.
[PUBMED Abstract]
-
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.
-
Bravo EL, Gifford RW Jr: Current concepts. Pheochromocytoma: diagnosis, localization and management. N Engl J Med 311 (20): 1298-303, 1984.
[PUBMED Abstract]
-
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.
-
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]
-
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]
-
Shapiro B, Fig LM: Management of pheochromocytoma. Endocrinol Metab Clin North Am 18 (2): 443-81, 1989.
[PUBMED Abstract]
-
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]
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]
Current Clinical Trials
Check for U.S. clinical trials from NCI's PDQ Cancer Clinical Trials Registry that are now accepting patients with recurrent pheochromocytoma 9. 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 6.
References
-
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.
-
Remine WH, Chong GC, Van Heerden JA, et al.: Current management of pheochromocytoma. Ann Surg 179 (5): 740-8, 1974.
[PUBMED Abstract]
-
Drasin H: Treatment of malignant pheochromocytoma. West J Med 128 (2): 106-11, 1978.
[PUBMED Abstract]
-
Brennan MF, Keiser HR: Persistent and recurrent pheochromocytoma: the role of surgery. World J Surg 6 (4): 397-402, 1982.
[PUBMED Abstract]
-
Shapiro B, Fig LM: Management of pheochromocytoma. Endocrinol Metab Clin North Am 18 (2): 443-81, 1989.
[PUBMED Abstract]
-
Manger WM, Gifford RW: Pheochromocytoma. New York: Springer-Verlag, 1977.
-
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.
-
Bravo EL, Gifford RW Jr: Current concepts. Pheochromocytoma: diagnosis, localization and management. N Engl J Med 311 (20): 1298-303, 1984.
[PUBMED Abstract]
-
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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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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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 12. 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. Changes to This Summary (01/03/2008)
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