title: The efficacy and safety of everolimus for the treatment of progressive gastroenteropancreatic neuroendocrine tumors: A multi-institution observational study in Taiwan.
abstract: OBJECTIVE
  Everolimus is an inhibitor of mTOR, approved for treatment of advanced pancreatic neuroendocrine tumors (NETs). The purpose of this observational study was to evaluate the efficacy and safety of everolimus in treatment of progressive, advanced gastroenteropancreatic neuroendocrine tumors (GEP-NETs) in Taiwan.
  
  
  METHODS
  Fifty-three patients with progressive, advanced GEP-NETs who received everolimus treatment between January 2008 and August 2014 were selected. Patient characteristics, tumor features, safety profiles and treatment efficacy were retrospectively analyzed.
  
  
  RESULTS
  Mean follow-up duration was 23.7 (1.2-70) months and 37 of 53 patients (69.8%) remained alive at the end of study. The one- and two-year overall survival rates were 90.5% and 75.4%, respectively. The median progression-free survival (PFS) was 18.9 (95% confidence interval; 10.9-26.8) months. Partial response was observed in 15 (28.3%) patients, 29 (54.7%) patients had stable disease and nine (17%) patients had progressive disease. Patients with World Health Organization (WHO) grade I NETs, nonfunctional tumors and liver metastasis burden <10% had significantly better PFS with everolimus treatment. Adverse events observed were stomatitis (35.8%), hyperglycemia (22.6%) and rash (18.8%). Seven (15.4%) patients experienced severe adverse events (grade 3 or more), including hyperglycemia (4.4%), anemia (4.4%), fatigue (2.2%) and elevated liver function (2.2%). One (2.2%) patient died from grade 5 interstitial pneumonitis.
  
  
  CONCLUSIONS
  Everolimus was an effective treatment for Taiwanese patients with progressive advanced GEP-NETs. Patients with nonfunctional NETs had a trend toward longer PFS, whereas patients with liver metastases burden <10% had a trend toward longer overall survival time receiving everolimus treatment.
authors.affiliation: Division of Hematology-Oncology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Chien-Ting
authors.initials: CT
authors.lastname: Liu
authors.affiliation: Taipei Veterans General Hospital, Division of Hematology & Oncology- Department of Medicine, Taipei, Taiwan.
authors.forename: Ming-Huang
authors.initials: MH
authors.lastname: Chen
authors.affiliation: Division of Hematology-Oncology, Linkou Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan.
authors.forename: Jen-Shi
authors.initials: JS
authors.lastname: Chen
authors.affiliation: National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan.|Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan.|Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
authors.forename: Li-Tzong
authors.initials: LT
authors.lastname: Chen
authors.affiliation: Department of Surgery, National Cheng Kung University Hospital, Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Yan-Shen
authors.initials: YS
authors.lastname: Shan
authors.affiliation: Chang Gung Memorial Hospital-Chiayi, Division of Hematology and Oncology- Department of Internal Medicine-, Chang Gung University College of Medicine, Chiayi, Taiwan.
authors.forename: Chang-Hsien
authors.initials: CH
authors.lastname: Lu
authors.affiliation: Division of Hematology-Oncology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Yu-Li
authors.initials: YL
authors.lastname: Su
authors.affiliation: Division of Hematology and Oncology, Department of Medicine, Changhua Show-Chwan Memorial Hospital, Changhua, Taiwan.
authors.forename: Fan-Chen
authors.initials: FC
authors.lastname: Ku
authors.affiliation: Division of Hematology-Oncology, Linkou Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan.
authors.forename: Wen-Chi
authors.initials: WC
authors.lastname: Chou
authors.affiliation: Division of Hematology-Oncology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
authors.forename: Yen-Yang
authors.initials: YY
authors.lastname: Chen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000740:Anemia / Q000139:chemically induced; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D018450:Disease Progression; D018572:Disease-Free Survival; D003875:Drug Eruptions / Q000209:etiology; D000068338:Everolimus / Q000009:adverse effects / Q000627:therapeutic use*; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006943:Hyperglycemia / Q000139:chemically induced; D007414:Intestinal Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D008113:Liver Neoplasms / Q000556:secondary*; D017563:Lung Diseases, Interstitial / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D018358:Neuroendocrine Tumors / Q000188:drug therapy* / Q000473:pathology*; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D012189:Retrospective Studies; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D013280:Stomatitis / Q000139:chemically induced; D015996:Survival Rate; D013624:Taiwan; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D000068338:Everolimus
keywords: everolimus; gastroenteropancreatic neuroendocrine tumors; neuroendocrine tumor