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Exp Clin Endocrinol Diabetes 2019; 127(02/03): 117-128
DOI: 10.1055/a-0715-1888
Review
© Georg Thieme Verlag KG Stuttgart · New York

Metastatic Phaeochromocytoma: Spinning Towards More Promising Treatment Options

Svenja Nölting
1   Medizinische Klinik und Poliklinik IV, Interdisciplinary Center of Neuroendocrine Tumours of the GastroEnteroPancreatic System (GEPNET-KUM), Klinikum der Universität München (KUM), Ludwig-Maximilians-University, Munich, Germany
,
Ashley Grossman
2   Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, Royal Free Hospital ENETS Centre of Excellence, London, and Barts and the London Scool of Medicine, London, UK
,
Karel Pacak
3   Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA
› Author Affiliations
Further Information

Publication History

received 17 May 2018
revised 15 August 2018

accepted 23 August 2018

Publication Date:
20 September 2018 (online)

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Abstract

Phaeochromocytomas (PCC) and paragangliomas (PGL) are rare tumours arising from the chromaffin cells of the adrenal medulla (PCC) or the paraganglia located outside the adrenal gland (PGL). However, their incidence is likely to be underestimated; around 10% of all PCC/PGL are metastatic, with higher metastatic potential of PGLs compared to PCCs. If benign, surgery is the treatment of choice, but if metastatic, therapy is challenging. Here we review the currently existing therapy options for metastatic PCCs/PGLs including conventional chemotherapy (the original Averbuch scheme, but updated), radiopharmaceutical treatments (131I-MIBG, 90Y- and 177Lu-DOTATATE) and novel targeted therapies (anti-angiogenic tyrosine kinase inhibitors and mTORC1 inhibitors), emphasising future therapeutic approaches (HIF-2α and PARP inhibitors, temozolomide alone, metronomic temozolomide, somatostatin analogues) based on the oncogenic signalling pathways related to three different clusters comprising more than 20 well-characterised PCC/PGL susceptibility genes. We suggest that targeted combination therapies including repurposed agents may offer more effective future options worthy of exploration.

Key words

Malignant phaeochromocytoma - therapy - oncogenic signalling
 

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