title: High-dose intramuscular octreotide in patients with acromegaly inadequately controlled on conventional somatostatin analogue therapy: a randomised controlled trial.
abstract: OBJECTIVE
  In acromegaly, 25-50% of patients respond inadequately to conventional long-acting somatostatin analogue (SSA) therapy. Response may be improved by increasing SSA frequency or dose. This study evaluated the biochemical efficacy and safety of high-dose octreotide in patients with acromegaly.
  
  
  METHODS
  A 24-week prospective, multicentre, randomised, open-label trial conducted from 12 December 2005 to 23 October 2007 in patients with persistently uncontrolled acromegaly despite > or =6 month conventional SSA therapy.
  
  
  METHODS
  Patients with > or =50% reduction in GH levels during previous SSA treatment were randomised to high-dose (60 mg/28 days) or high-frequency (30 mg/21 days) octreotide i.m. injection. Primary end-points were week 12 and 24 reduction in serum IGF1 and GH from baseline. Secondary end points included IGF1 normalisation and tumour shrinkage rates, and safety/tolerability evaluations.
  
  
  RESULTS
  Significantly, more patients (10 out of 11) achieved week 24 IGF1 reduction in the high-dose than the high-frequency group (8 out of 15; P<0.05). In the high-dose group only, week-24 IGF1 values were significantly reduced (P=0.02) versus baseline. Normalisation of IGF1 occurred only with the high-dose regimen (4/11; P=0.02). Out of 14 patients experiencing adverse events, 5 reported drug-related gastrointestinal effects. No dose-response relationship was seen. Safety parameters were similar between treatment groups, apart from a slight decrease in HbA1c in the high-dose group only.
  
  
  CONCLUSIONS
  High-dose octreotide treatment is safe and effective (normalisation of IGF1 levels) in a subset of patients with active acromegaly inadequately controlled with long-term SSA. Individualised octreotide doses up to 60 mg/28 days may improve outcomes of SSA therapy.
authors.affiliation: Department of Medical and Surgical Sciences, University of Brescia, 25123 Brescia, Italy. a.giustina@libero.it
authors.forename: Andrea
authors.initials: A
authors.lastname: Giustina
authors.forename: Stefania
authors.initials: S
authors.lastname: Bonadonna
authors.forename: Giovanna
authors.initials: G
authors.lastname: Bugari
authors.forename: Annamaria
authors.initials: A
authors.lastname: Colao
authors.forename: Renato
authors.initials: R
authors.lastname: Cozzi
authors.forename: Salvatore
authors.initials: S
authors.lastname: Cannavo
authors.forename: Laura
authors.initials: L
authors.lastname: de Marinis
authors.forename: Ettore
authors.initials: E
authors.lastname: Degli Uberti
authors.forename: Fausto
authors.initials: F
authors.lastname: Bogazzi
authors.forename: Gherardo
authors.initials: G
authors.lastname: Mazziotti
authors.forename: Francesco
authors.initials: F
authors.lastname: Minuto
authors.forename: Marcella
authors.initials: M
authors.lastname: Montini
authors.forename: Ezio
authors.initials: E
authors.lastname: Ghigo
mesh_terms: D000172:Acromegaly / Q000097:blood / Q000188:drug therapy*; D000328:Adult; D000368:Aged; D005260:Female; D019382:Human Growth Hormone / Q000097:blood; D006801:Humans; D007273:Injections, Intramuscular; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D015282:Octreotide / Q000008:administration & dosage*; D011446:Prospective Studies; D013004:Somatostatin / Q000008:administration & dosage / Q000031:analogs & derivatives*
chemical_list: D019382:Human Growth Hormone; D013004:Somatostatin; D007334:Insulin-Like Growth Factor I; D015282:Octreotide