title: Pasireotide monotherapy in Cushing's disease: a single-centre experience with 5-year extension of phase III Trial.
abstract: OBJECTIVE
  A recent phase III randomized controlled trial (NCT00434148) showed efficacy of pasireotide in the treatment of patients with Cushing's disease (CD). Patients were invited to participate in an extension phase of the protocol and a subgroup had a sustained response. We report the experience with 4 patients in our center of which 2 full responders have completed 5.5 and 4.25 years of treatment with disease control.
  
  
  METHODS
  The trial protocol was described previously. The extension phase consisted of 3-monthly visits with clinical, biochemical, and imaging evaluation and investigator-driven pasireotide titration. Research charts were retrospectively analyzed.
  
  
  RESULTS
  Four patients with persistent CD following pituitary surgery completed the first 6 months of the trial and 3 continued in the next 6 month open-label phase. Two patients with baseline urinary free cortisol (UFC) 5.3-6.7 times the upper limit of normal had a rapid sustained response to pasireotide and entered the extension phase after 12 months. They remain in clinical and biochemical disease remission and 1 patient now only requires 300 μg daily of pasireotide. All 4 patients developed glucose intolerance; however, the two patients in the extension phase were eventually able to discontinue all diabetes pharmacotherapy. Adverse events included second degree atrioventicular block type 1 without QT prolongation in a patient with pre-existing sinus bradycardia, and symptomatic cholelithiasis requiring cholecystectomy in a second patient.
  
  
  CONCLUSIONS
  Pasireotide therapy can provide normalization of UFC and of clinical symptoms and signs of CD during up to 5 years of follow-up. This study demonstrates the possible recuperation of normoglycemia after continued use of pasireotide and control of underlying hypercortisolemia. Longer-term monitoring for potential adverse events related to continued use of pasireotide is indicated.
authors.affiliation: Division of Endocrinology, Department of Medicine and Research Center, Centre Hospitalier de l'Université de Montréal (CHUM)-Hotel-Dieu, 3850 Saint-Urbain Street, Montreal, QC, H2W 1T8, Canada.
authors.forename: Jessica
authors.initials: J
authors.lastname: MacKenzie Feder
authors.forename: Isabelle
authors.initials: I
authors.lastname: Bourdeau
authors.forename: Sophie
authors.initials: S
authors.lastname: Vallette
authors.forename: Hugues
authors.initials: H
authors.lastname: Beauregard
authors.forename: Louis-Georges
authors.initials: LG
authors.lastname: Ste-Marie
authors.forename: André
authors.initials: A
authors.lastname: Lacroix
mesh_terms: D000328:Adult; D015331:Cohort Studies; D004562:Electrocardiography / Q000187:drug effects; D005260:Female; D018149:Glucose Intolerance / Q000188:drug therapy / Q000209:etiology; D006801:Humans; D006854:Hydrocortisone / Q000652:urine; D008297:Male; D008875:Middle Aged; D047748:Pituitary ACTH Hypersecretion / Q000188:drug therapy*; D013004:Somatostatin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013575:Syncope / Q000139:chemically induced; D016896:Treatment Outcome
chemical_list: D013004:Somatostatin; C517782:pasireotide; D006854:Hydrocortisone