Context: Pheochromocytomas are rare tumors of predominantly adrenal origin that often produce and secrete catecholamines. Malignancy occurs in a variable percentage of cases depending on genetic background and tumor location. Definitive diagnosis relies on the detection of distant metastases. Treatments for malignant pheochromocytoma include surgical debulking, pharmacological control of hormone-mediated symptoms, targeted methods such as external irradiation, and systemic antineoplastic therapy. Different agents and protocols for this purpose are reviewed and their therapeutic potential is discussed.

Evidence Acquisition: Literature on antineoplastic therapies for malignant pheochromocytoma was identified by searching the PubMed database with restriction to articles published in English during the past 30 years.

Evidence Synthesis: Due to the rarity of the condition, no randomized clinical trials concerning the treatment of malignant pheochromocytoma have been performed. The strategy established best is ¹³¹I-MIBG therapy, which is well tolerated. Similar to cytotoxic chemotherapy with cyclophosphamide, vincristine, and dacarbazine (CVD), MIBG can induce remission for a limited period in a significant proportion of patients. Octreotide as a single agent seems to be largely ineffective.

Conclusions: MIBG radiotherapy and CVD chemotherapy are comparable with respect to response rate and toxicity. It is unclear whether combining both can improve the outcome. Future developments may include new multimodal concepts with focus on inhibition of angiogenetic factors and heat shock protein 90. Any present or new therapeutic approach must take into account the highly variable natural course of the disease.