Treatment for Malignant Pheochromocytomas and Paragangliomas: 5 Years of Progress

Abstract

The manuscript will describe the clinical predictors of survivorship and their influence on the first TNM staging classification for pheochromocytomas and sympathetic paragangliomas, the treatment of hormonal complications, and the rationale that supports the resection of the primary tumor and metastases in patients with otherwise incurable disease. Therapeutic options for patients with bone metastasis to the spine will be presented. The manuscript will also review chemotherapy and propose a maintenance regimen with dacarbazine for patients initially treated with cyclophosphamide, vincristine, and dacarbazine. Finally, the manuscript will review preliminary results of several phase 2 clinical trials of novel radiopharmaceutical agents and tyrosine kinase inhibitors. MPPGs are very rare neuroendocrine tumors. MPPGs are usually characterized by a large tumor burden, excessive secretion of catecholamines, and decreased overall survival. Recent discoveries have enhanced our knowledge of the pathogenesis and phenotypes of MPPG. This knowledge is leading to a better understanding of the indications and limitations of the currently available localized and systemic therapies as well as the development of phase 2 clinical trials for novel medications.

Management of Pheochromocytoma in Dakar: Diagnostic and Therapeutic Advances throughout 16 Cases

“…CVD chemotherapy can be indicated to treat patients presenting an evolutive disease, and the patients who well respond to CVD can gain from a maintaining treatment with the dacarbazine. Clinical trials are ongoing for the use of radio-pharmaceutical agents, inhibitors of tyrosine kinase and immunotherapies [20].…”

Interventional radiology of the adrenal glands: current status

“…Pheochromocytomas embolization alone has proved to be insufficient for long-term symptom and hormone control and surgical resection remains the gold standard of treatment, also because approximately 15-17% of pheochromocytomas are discovered to be malignant at the pathological examination (145).…”

Metastatic Phaeochromocytoma: Spinning Towards More Promising Treatment Options

“…Besides other sporadically-used chemotherapy protocols including cisplatin, 5-fluorouracil, methotrexate, ifosfamide and streptozotocin which show low evidence to support their clinical use [54,55], the best studied chemotherapy protocol for advanced PCC/PGL combines cyclophosphamide, vincristine, and dacarbazine (CVD) according to the Averbuch scheme (cyclophosphamide 750 mg/ m 2 , vincristine 1.4 mg/m 2 , and dacarbazine 600 mg/m 2 on day 1 and dacarbazine 600 mg/m 2 on day 2) [56]. However, all studies are retrospective and prognostic factors indicating metastatic behaviour such as size and location of the primary tumour, size, location and the timing of metastases, progression prior to chemotherapy, and SDHB mutation status, are frequently missing [55]. A meta-analysis of the largest studies on CVD showed a partial response concern-ing tumour size in 37 % of patients [57].…”

“…However, the side effects of vincristine may include peripheral sensory and autonomic neuropathy [63] while rare cases of leukaemia and myelodysplastic syndrome have been observed [58]. Whether adjuvant treatment with 4-6 cycles of CVD after surgery in patients with positive predictors of metastatic potential could improve PFS and OS has not yet been studied [55].…”

“…The long-term tolerability of temozolomide monotherapy may be better as compared to maintenance therapy with CVD. Maintenance with dacarbazine or temozolomide alone after 6-9 cycles of CVD may be reasonable for patients who initially responded to CVD (partial radiographic response or disease stabilisation) [55,64]. If temozolomide monotherapy is not effective or not tolerated at standard doses, a metronomic scheme with long-term low-dose temozolomide (75 mg/m 2 /d with a schedule of 3 weeks on treatment followed by 1 week off treatment) in combination with high-dose lanreotide autogel (120 mg s.c. every 14 days) might stabilise PCCs/PGLs with low MGMT levels and MGMT hypermethylation, as recently published for two patients [68].…”