uu.seUppsala University Publications
Change search
ReferencesLink to record
Permanent link

Direct link
Everolimus in the treatment of patients with advanced pancreatic neuroendocrine tumors: latest findings and interpretations
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
2013 (English)In: Therapeutic Advances in Gastroenterology, ISSN 1756-283X, Vol. 6, no 5, 412-419 p.Article in journal (Refereed) Published
Abstract [en]

Pancreatic neuroendocrine tumors (pNETs) are a heterogeneous group of neoplasms with various clinical presentations. More than half of patients present with so-called nonfunctioning tumors with no hormone-related symptoms, whereas other tumors produce symptoms like gastric problems, ulcers, hypoglycemia, skin rash and diarrhea related to hormone production. The traditional treatment for pNETs over the last three decades has been cytotoxic agents, mainly streptozotocin plus 5-fluorouracil or doxorubicin. Most recently two new compounds have been registered worldwide for the treatment of pNETs, the mammalian target of rapamycin (mTOR) inhibitor everolimus and the tyrosine kinase inhibitor sunitinib. This paper concentrates on the use of mTOR inhibitors and the mechanisms of action. The mTOR pathway is altered in a number of pNETs. Everolimus (RAD001) is an orally active rapamycin analog and mTOR inhibitor. It blocks activity of the mTOR pathway by binding with high affinity to the cytoplasmic protein FKBP-12. The efficacy of everolimus in pNETs has been demonstrated in two multicenter studies (RADIANT 1 and 3). The RADIANT 3 study was a randomized controlled study in pNETs of everolimus 10 mg/day versus placebo, showing an increased progression-free survival (11.7 months versus 4.6 months) and hazard ratio of 0.35 (p < 0.001). Current studies indicate that there is strong evidence to support the antitumor effect of rapalogs in pNETs. However, significant tumor reduction is very rarely obtained, usually in less than 10% of treated patients. Therefore, these drugs may be more effective in combination with other anticancer agents, including chemotherapy, targeted therapies as well as peptide receptor radiotherapy.

Place, publisher, year, edition, pages
2013. Vol. 6, no 5, 412-419 p.
Keyword [en]
Neuroendocrine, Carcinoid, Pancreatic, Everolimus, mTOR, Tumor, NETs, RADIANT, Afinitor, Sunitinib
National Category
Gastroenterology and Hepatology
URN: urn:nbn:se:uu:diva-227216DOI: 10.1177/1756283X13496970ISI: 000335749400007OAI: oai:DiVA.org:uu-227216DiVA: diva2:728649
Available from: 2014-06-24 Created: 2014-06-24 Last updated: 2014-06-24Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full text

Search in DiVA

By author/editor
Öberg, Kjell
By organisation
Department of Medical Sciences
In the same journal
Therapeutic Advances in Gastroenterology
Gastroenterology and Hepatology

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 147 hits
ReferencesLink to record
Permanent link

Direct link