PMID- 28286565
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240324
IS  - 1756-283X (Print)
IS  - 1756-2848 (Electronic)
IS  - 1756-283X (Linking)
VI  - 10
IP  - 1
DP  - 2017 Jan
TI  - Everolimus in the management of metastatic neuroendocrine tumours.
PG  - 132-141
LID - 10.1177/1756283X16674660 [doi]
AB  - Neuroendocrine tumours are increasing in incidence and cause a variety of 
      symptoms. The mammalian target of rapamycin (mTOR) pathway plays a key role in 
      neuroendocrine tumour (NET) pathogenesis, leading to increased lipid synthesis, 
      protein synthesis and cellular growth. Upregulation of this pathway is noted in 
      both hereditary and sporadic NETs. This understanding has led to investigations 
      of mTOR inhibitors as therapy for metastatic NETs. After promising preclinical 
      findings, everolimus, an mTOR inhibitor, was trialled in the RADIANT-1-4 studies 
      on patients with advanced, well differentiated NETs. RADIANT-3 and RADIANT-4 
      established the efficacy of everolimus in improving progression-free survival 
      (PFS) for metastatic NET of pancreatic, lung and gastrointestinal origin, leading 
      to the US Food and Drug Administration (FDA) approval for its use in tumour 
      control in those settings. Everolimus treatment is generally well tolerated; 
      common adverse events include stomatitis, diarrhoea, rash and hyperglycaemia. 
      Although discontinuation rates are low, many patients may require dose 
      modification to successfully continue therapy. The combination of everolimus with 
      somatostatin analogues (SSAs) (such as octreotide or pasireotide) or other 
      targeted agents such as bevacizumab has not produced additional incremental 
      benefit, and dual biologic therapy is not used widely. Ongoing trials are 
      investigating everolimus compared with chemotherapy, optimal sequencing of 
      therapy and combination of everolimus with radiotherapy. Future research should 
      concentrate on identification of predictive biomarkers for benefit from mTOR 
      therapy and include quality of life as a measure.
FAU - Chan, David L
AU  - Chan DL
AD  - Odette Cancer Centre, Toronto, ON, Canada.
FAU - Segelov, Eva
AU  - Segelov E
AD  - St Vincent's Hospital, New South Wales, Australia.
FAU - Singh, Simron
AU  - Singh S
AD  - Odette Cancer Centre, 2075 Bayview Avenue, Room T2 047, Toronto, ON, Canada M4N 
      3M5.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20161025
PL  - England
TA  - Therap Adv Gastroenterol
JT  - Therapeutic advances in gastroenterology
JID - 101478893
PMC - PMC5330615
OTO - NOTNLM
OT  - RADIANT
OT  - everolimus
OT  - neuroendocrine tumors
OT  - review
COIS- Conflict of interest statement: DC has received honoraria from Ipsen and travel 
      funding from Novartis. SS has received honoraria and travel funding from Ipsen, 
      Pfizer and Novartis.
EDAT- 2017/03/14 06:00
MHDA- 2017/03/14 06:01
PMCR- 2017/01/01
CRDT- 2017/03/14 06:00
PHST- 2017/03/14 06:00 [entrez]
PHST- 2017/03/14 06:00 [pubmed]
PHST- 2017/03/14 06:01 [medline]
PHST- 2017/01/01 00:00 [pmc-release]
AID - 10.1177_1756283X16674660 [pii]
AID - 10.1177/1756283X16674660 [doi]
PST - ppublish
SO  - Therap Adv Gastroenterol. 2017 Jan;10(1):132-141. doi: 10.1177/1756283X16674660. 
      Epub 2016 Oct 25.