title: Everolimus: a new treatment option for advanced pancreatic neuroendocrine tumors.
abstract: OBJECTIVE
  To present the current clinical evidence on everolimus for use in pancreatic neuroendocrine tumors (pNET).
  
  
  METHODS
  A literature search was performed using PubMed and MEDLINE (1946-March 2012). Search terms were everolimus, RAD001, mTOR inhibitor, and pancreatic neuroendocrine tumors. Abstracts from the American Society of Clinical Oncology 2000-2012 meetings and Food and Drug Administration (FDA) reviews were searched to obtain otherwise unpublished data. The national clinical trials registry was searched for current and future studies of everolimus in pNET.
  
  
  METHODS
  Clinical studies available in the English language describing the pharmacology, pharmacokinetics, clinical activity, and safety of everolimus in pNET were included. All peer-reviewed, clinically relevant publications were reviewed for inclusion.
  
  
  RESULTS
  Everolimus is an oral mammalian target of rapamycin (mTOR) inhibitor approved by the FDA in May 2011 for the treatment of progressive, advanced pNET. Everolimus exerts its effect by inhibiting multiple downstream pathways of mTOR, which decreases cell proliferation, survival, and angiogenesis. Its pNET indication was based on the results of RADIANT-3, a Phase 3 trial demonstrating increased median progression-free survival (11 months) with everolimus 10 mg orally once daily compared to placebo (4.6 months). Everolimus was well tolerated in clinical trials. The most commonly reported adverse events included stomatitis, rash, diarrhea, fatigue, infections, nausea, and decreased appetite. Grade 3/4 events including anemia, thrombocytopenia, pneumonitis, and hyperglycemia occurred in approximately 5% of patients.
  
  
  CONCLUSIONS
  Based on review of the available literature, everolimus is a safe and effective treatment option for patients with low- to intermediate-grade, unresectable or metastatic pNET that have progressed on prior therapies. Until results of head-to-head, randomized controlled trials are conducted to compare everolimus to other treatment options, it cannot be said whether everolimus is more efficacious or tolerable than other treatment options.
authors.affiliation: Department of Clinical Pharmacy, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Aurora, CO, USA. Lisa.A.Thompson@ucdenver.edu
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Thompson
authors.forename: Miryoung
authors.initials: M
authors.lastname: Kim
authors.forename: Sarah D
authors.initials: SD
authors.lastname: Wenger
authors.forename: Cindy L
authors.initials: CL
authors.lastname: O'Bryant
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000068338:Everolimus; D006801:Humans; D018358:Neuroendocrine Tumors / Q000188:drug therapy*; D010190:Pancreatic Neoplasms / Q000188:drug therapy*; D020123:Sirolimus / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors
chemical_list: D000970:Antineoplastic Agents; D000068338:Everolimus; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus