Horm Metab Res 2009; 41(9): 697-702
DOI: 10.1055/s-0029-1220687
Humans, Clinical

© Georg Thieme Verlag KG Stuttgart · New York

Novel and Evolving Therapies in the Treatment of Malignant Phaeochromocytoma: Experience with the mTOR Inhibitor Everolimus (RAD001)

M. R. Druce 1 , G. A. Kaltsas 2 , M. Fraenkel 3 , D. J. Gross 3 , A. B. Grossman 1
  • 1Department of Endocrinology, Barts and the London School of Medicine, London, UK
  • 2Department of Pathophysiology, National University of Athens, Athens, Greece
  • 3Endocrinology & Metabolism Service, Department of Medicine, Hadassah-Hebrew University Medical Center, Jerusalem, Israel
Further Information

Publication History

received 08. 12. 2008

accepted 24. 03. 2009

Publication Date:
07 May 2009 (online)


Phaeochromocytoma and paraganglioma are rare neuroendocrine tumours (NETS). They may be benign or malignant but the pathological distinction is mainly made when metastases are present. Available treatments in the form of surgery, chemotherapy, and radionuclide therapy may improve symptoms and biochemical markers, but the results for the control of tumour bulk are less favourable. Furthermore, responses to treatment are frequently short-lived. This short review outlines the main molecular and histological features of malignant phaeochromocytoma and the difficulties in differentiating between benign and malignant disease. We list current therapies used for malignant pheochromocytoma; however, these generally achieve relatively low success rates. Hence, there is a need for new and more effective therapies. In vitro studies have implicated the PI3/Akt/mTOR pathway in the pathogenesis of malignant NETS, including phaeochromocytoma. Everolimus (RAD001, Novartis UK) is a compound that inhibits mTOR (mammalian Target Of Rapamycin) signalling. We have used RAD001 in four patients with progressive malignant paraganglioma/phaeochromocytoma in addition to other therapies (with institutional approval for compassionate use), and evaluated the effects of this treatment. We outline these four cases and review the theoretical background for this therapy, although the outcomes were relatively disappointing.



Prof. A. B. Grossman

Department of Endocrinology

St. Bartholomew's Hospital

West Smithfield

London EC1A 7BE


Phone: +44/20/7601 83 43

Fax: +44/20/7601 85 05

Email: [email protected]