High-dose intramuscular octreotide in patients with acromegaly inadequately controlled on conventional somatostatin analogue therapy: a randomised controlled trial.
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.
Giustina
Andrea
A
Department of Medical and Surgical Sciences, University of Brescia, 25123 Brescia, Italy. a.giustina@libero.it
Bonadonna
Stefania
S
Bugari
Giovanna
G
Colao
Annamaria
A
Cozzi
Renato
R
Cannavo
Salvatore
S
de Marinis
Laura
L
Degli Uberti
Ettore
E
Bogazzi
Fausto
F
Mazziotti
Gherardo
G
Minuto
Francesco
F
Montini
Marcella
M
Ghigo
Ezio
E
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*
D019382:Human Growth Hormone; D013004:Somatostatin; D007334:Insulin-Like Growth Factor I; D015282:Octreotide