OBJECTIVE: Somatostatin analogue treatment is first-line medical therapy for acromegaly. This study compared the efficacy and tolerability of titrated doses of the long-acting somatostatin analogue preparation lanreotide Autogel® with fixed doses and with lanreotide prolonged release (PR) 30 mg microparticles. PATIENTS: Patients entering the initial study had received a diagnosis of active acromegaly within the previous 5 years. DESIGN: This open, comparative, multicentre study was a 1-year extension of a previous trial during which patients with acromegaly had switched from lanreotide PR 30 mg microparticles injected intramuscularly every 7, 10 or 14 days, for at least 3 months, to one of three fixed doses of lanreotide Autogel® (120, 90, or 60 mg every 28 days, respectively). In this extension study, patients continued to receive 60, 90, or 120 mg of lanreotide Autogel® by deep subcutaneous injection every 28 days for 1 year. Doses could be titrated at entry or after four or eight injections, according to the GH/IGF-I response (dose increased if GH > 2.5 μg/l, or decreased if GH < 1 μg/l with normal IGF-I). MEASUREMENTS: Mean ± SEM GH and IGF-I concentrations were analysed and gallbladder echography performed at weeks 0, 16, 32, and 48. Acromegaly symptoms were recorded monthly and tolerance and side-effects were monitored throughout the study. RESULTS: In total, 130 patients entered this extension phase. After 1 year of treatment with titrated doses of lanreotide Autogel®, mean GH (2.4±0.2 μg/l) and IGF-I (287 ± 12 μg/l) concentrations were significantly lower than with lanreotide microparticles (GH, 2.8 ± 0.2 μg/l, P < 0.001; IGF-I, 332 ± 15 μg/l, P < 0.01) or with fixed-dose lanreotide Autogel® (GH, 3.0 ± 0.2 μg/l, P < 0.001; IGF-I, 310 ± 14 μg/l, P = 0.02). GH hypersecretion was reduced to ≤2.5 μg/l in 68% of patients with titrated-dose lanreotide Autogel® compared with 49% with microparticles (P < 0.001) and 56% with fixed-dose lanreotide Autogel® (P ≤ 0.005). In the 65 patients who did not require any dose titration, there was no substantial change in serum lanreotide concentration, GH or IGF-I levels over the 12-month study duration. Acromegaly was effectively controlled (GH ≤ 2.5 μg/l and normalized IGF-I) in significantly more patients (43%) compared with microparticles (32%; P < 0.05). There was a trend for improved control of acromegalic symptoms with dose titration, whereas the incidence of gastrointestinal symptoms and local tolerance was similar with lanreotide Autogel® and lanreotide microparticles. Gallbladder echographies showed new lithiasis in 8% of lanreotide Autogel® patients. CONCLUSION: Dose titration of lanreotide Autogel® improved GH and IGF-I control in patients with acromegaly beyond that achieved using fixed doses of lanreotide Autogel® or lanreotide microparticles. Titrated long-term lanreotide Autogel® treatment is well tolerated.
ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism