title: NeuroEndocrine Tumor Therapy with Lutetium-177-octreotate and Everolimus (NETTLE): A Phase I Study.
abstract: OBJECTIVE
  To establish the optimal safe dose of everolimus in combination with (177)Lu-octreotate peptide receptor radionuclide therapy (PRRT) of advanced progressive gastro-entero pancreatic neuroendocrine tumors (GEP-NETs) and to define dose-limiting toxicity.
  
  
  METHODS
  Patients with advanced unresectable progressive well-differentiated GEP-NETS avid for (68)Ga-octreotate on positron emission tomography-computed tomography imaging underwent PRRT with four cycles of 7.8 GBq (177)Lu-octreotate at 8 week intervals. Successive cohorts of 3 patients received escalating doses of everolimus comprising 5, 7.5, and 10 mg daily for 24 weeks.
  
  
  RESULTS
  Sixteen patients comprised 4 at 5 mg, 9 at 7.5 mg, and 3 at 10 mg everolimus. Patient cohorts at 5 and 7.5 mg received 83% and 80% of the total planned dose of everolimus over 24 weeks. All patients required dose reduction or complete cessation of everolimus at the 10 mg level, which induced neutropenia and thrombocytopenia, and reduced creatinine clearance. The overall response rate was 44% (7 of 16 patients), and no patient progressed over the 6 month period of treatment. Four of 5 pancreatic NET patients achieved PR 80%. No patient progressed on study.
  
  
  CONCLUSIONS
  In combination, PRRT with (177)Lu-octreotate, the maximum tolerated dose of everolimus is 7.5 mg daily.
authors.affiliation: 1 Department of Oncology, Fremantle Hospital, The University of Western Australia , Fremantle, Australia .
authors.forename: Phillip G
authors.initials: PG
authors.lastname: Claringbold
authors.affiliation: 2 Department of Nuclear Medicine, Fremantle Hospital, The University of Western Australia , Fremantle, Australia .
authors.forename: J Harvey
authors.initials: JH
authors.lastname: Turner
mesh_terms: D000328:Adult; D000368:Aged; D000068338:Everolimus / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008187:Lutetium / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D018358:Neuroendocrine Tumors / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology; D011877:Radionuclide Imaging; D016896:Treatment Outcome
chemical_list: D008187:Lutetium; D000068338:Everolimus
keywords: PRRT; molecular therapy NET; targeted radionuclide-biological-therapy