title: Pasireotide can induce sustained decreases in urinary cortisol and provide clinical benefit in patients with Cushing's disease: results from an open-ended, open-label extension trial.
abstract: OBJECTIVE
  Report the efficacy and safety of pasireotide sc in patients with Cushing's disease during an open-ended, open-label extension to a randomized, double-blind, 12-month, Phase III study.
  
  
  METHODS
  162 patients entered the core study. 58 patients who had mean UFC ≤ ULN at month 12 or were benefiting clinically from pasireotide entered the extension. Patients received the same dose of pasireotide as at the end of the core study (300-1,200 μg bid). Dose titration was permitted according to efficacy or drug-related adverse events.
  
  
  RESULTS
  40 patients completed 24 months' treatment. Of the patients who entered the extension, 50.0% (29/58) and 34.5% (20/58) had controlled UFC (UFC ≤ ULN) at months 12 and 24, respectively. The mean percentage decrease in UFC was 57.3% (95% CI 40.7-73.9; n = 52) and 62.1% (50.8-73.5; n = 33) after 12 and 24 months' treatment, respectively. Improvements in clinical signs of Cushing's disease were sustained up to month 24. The most frequent drug-related adverse events in patients who received ≥1 dose of pasireotide (n = 162) from core baseline until the 24-month cut-off were diarrhea (55.6%), nausea (48.1%), hyperglycemia (38.9%), and cholelithiasis (31.5%). No new safety issues were identified during the extension.
  
  
  CONCLUSIONS
  Reductions in mean UFC and improvements in clinical signs of Cushing's disease were maintained over 24 months of pasireotide treatment. The safety profile of pasireotide is typical for a somatostatin analogue, except for the frequency and degree of hyperglycemia; patients should be monitored for changes in glucose homeostasis. Pasireotide represents the first approved pituitary-targeted treatment for patients with Cushing's disease.
authors.affiliation: Medizinische Klinik IV, University of Munich, Munich, Germany.
authors.forename: Jochen
authors.initials: J
authors.lastname: Schopohl
authors.forename: Feng
authors.initials: F
authors.lastname: Gu
authors.forename: Robert
authors.initials: R
authors.lastname: Rubens
authors.forename: Luc
authors.initials: L
authors.lastname: Van Gaal
authors.forename: Jérôme
authors.initials: J
authors.lastname: Bertherat
authors.forename: Monica
authors.initials: M
authors.lastname: Ligueros-Saylan
authors.forename: Andrew
authors.initials: A
authors.lastname: Trovato
authors.forename: Gareth
authors.initials: G
authors.lastname: Hughes
authors.forename: Luiz R
authors.initials: LR
authors.lastname: Salgado
authors.forename: Marco
authors.initials: M
authors.lastname: Boscaro
authors.forename: Rosario
authors.initials: R
authors.lastname: Pivonello
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000652:urine; D004311:Double-Blind Method; D015536:Down-Regulation; D005060:Europe; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000652:urine*; D008297:Male; D008875:Middle Aged; D047748:Pituitary ACTH Hypersecretion / Q000175:diagnosis / Q000188:drug therapy* / Q000652:urine; D013004:Somatostatin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D015415:Biomarkers; D013004:Somatostatin; C517782:pasireotide; D006854:Hydrocortisone