A randomized, open-label, multicenter study to evaluate octreotide LAR with surgical therapy as primary therapy patients with acromegaly
A Colao1, H Bouterfa2, P Cappabianca3, P Caron4, E De Menis5, A Farrall6, M Gadelha7, A Reed8, M Reincke9, M Safari2, G T’Sjoen10 & R Cuneo11
Author affiliations
1II Policlinico II Università degli Studi di Napoli, Naples, Italy; 2Novartis Pharma AG, Basel, Switzerland; 3Universita degli Studi di Napoli Federico II, Naples, Italy; 4CHU de Rangueil-Larrey, Toulouse, France; 5Ospedale Generale Ca’Foncello, Treviso, Italy; 6University of Edinburgh, Edinburgh, United Kingdom; 7Hospital Universitário Clementino Fraga Filho – UFRJ, Rio de Janeiro, Brazil; 8University Hospital of Wales, Cardiff, United Kingdom; 9Klinikum der Universität München, Munich, Germany; 10University Hospital Gent, Gent, Belgium; 11Princess Alexandra Hospital, Brisbane, Australia.
This is the first prospective study to compare the efficacy and safety of medical therapy and surgery as primary therapy in acromegaly.
A total of 104 patients with untreated acromegaly were enrolled. Eighty-one patients randomized to receive either octreotide LAR 20 mg (n=40) or surgery (n=41) completed the 48 weeks treatment period, and constituted the population used for this analysis, regardless of response to treatment.
Biochemical response was assessed by changes in mean GH and IGF-I concentrations, determined at weeks 12, 24 and 48. Tumor size was assessed by contrast-enhanced MRI. Octreotide LAR-treated patients responding adequately (control of both GH and IGF-1) to treatment at either of the evaluations continued on the same dose, while partial responders (GH or IGF-1 control) had their dose titrated up to 30 mg at the following visit. Patients treated with surgery demonstrating a complete response at weeks 12 and 24 received no additional treatment, but those with a partial response commenced octreotide LAR.
Treatment success rates after 24 weeks of therapy were 43% and 51% for octreotide LAR and surgery groups, respectively. By week 48, these were 40% and 49%, respectively. At week 28, 49% had switched from surgery to octreotide LAR and 33% from octreotide LAR to surgery. Overall, 73% of patients treated with octreotide LAR had significant (>20%) tumor shrinkage over the 48-week study period, with a mean tumor volume reduction of 35% at the end of treatment.
This large prospective study confirms the effectiveness of octreotide LAR in the primary treatment of acromegaly, but also shows that its efficacy is similar to that of surgery. Given the good compliance, and low complication rate resulting from the medical treatment, primary therapy with octreotide LAR could be considered as first-line treatment for patients with acromegaly.