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.[2,3,4] 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.[6,7,8]

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]

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.
3. Drasin H: Treatment of malignant pheochromocytoma. West J Med 128 (2): 106-11, 1978.
4. Brennan MF, Keiser HR: Persistent and recurrent pheochromocytoma: the role of surgery. World J Surg 6 (4): 397-402, 1982.
5. Shapiro B, Fig LM: Management of pheochromocytoma. Endocrinol Metab Clin North Am 18 (2): 443-81, 1989.
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.
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.
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.