title: Role of everolimus in pancreatic neuroendocrine tumors.
abstract: Survival from pancreatic neuroendocrine tumors has not improved over the past two decades and, until recently, streptozocin was the last therapeutic agent approved for this malignancy. Everolimus blocks mTOR, which plays an integral role in cell growth, mitosis and angiogenesis. Abnormal PI3K-Akt/PKB-mTOR pathway signaling has been implicated in the pathogenesis of pancreatic neuroendocrine tumors. In a Phase III study, patients with low- and intermediate-grade advanced pancreatic neuroendocrine tumors were randomized to receive everolimus 10 mg/day or placebo. Median progression-free survival was significantly greater in patients treated with everolimus than placebo - 11 versus 4.6 months - and drug-related adverse events were consistent with the known side-effect profile of everolimus. Everolimus represents a significant treatment development for pancreatic neuroendocrine tumors.
authors.affiliation: UCL Cancer Institute, Paul O'Gorman Building, 72 Huntley Street, London, WC1E 6BT, UK.
authors.forename: Robert
authors.initials: R
authors.lastname: Goldstein
authors.forename: Tim
authors.initials: T
authors.lastname: Meyer
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D018572:Disease-Free Survival; D004353:Drug Evaluation, Preclinical; D000068338:Everolimus; D006801:Humans; D009367:Neoplasm Staging; D018358:Neuroendocrine Tumors / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016032:Randomized Controlled Trials as Topic; D020123:Sirolimus / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D000068338:Everolimus; D020123:Sirolimus