Efficacy of long-term lanreotide treatment in patients with acromegaly

Abstract

We investigated the effectiveness of lanreotide for the treatment of active acromegaly in a retrospectively multicenter case series including 53 patients (24 male, 29 female; mean age at diagnosis, 49.5 +/- 13.9 years) with acromegaly treated with lanreotide in nine different centers. Mean tumor diameter was 20 +/- 13 mm; mean basal levels of growth hormone (GH) and insulin-like growth factor I (IGF-I) were 21.3 +/- 26.3 and 579 +/- 177 mug/l, respectively. The primary mode of treatment was surgery in 70% of patients. Twenty-nine patients received only lanreotide (Prolonged Release, Autogel), whereas 24 subjects were also treated with octreotide at another treatment stage. Primary therapy with lanreotide was administered in five patients. Maximal monthly dose of lanreotide Autogel (n = 44) was 60 mg in 45%, 90 mg in 26%, 120 mg in 21% and 180 mg in 8%. During 36 months of lanreotide treatment, mean IGF-I levels decreased from 443 +/- 238 to 276 +/- 147 mug/l (P < 0.001), and mean GH levels, from 5.2 +/- 6.4 to 3.2 +/- 3.0 mug/l (P < 0.001). IGF-I levels normalized in 51% of patients and decreased by >50% towards normal in 32%; the normalization rate was higher in women (65%) than men (33%, P = 0.04). Safe random GH levels (</=2 mug/l) were achieved in 49% of patients. Both IGF-I normalization and safe GH levels were reached in 32% of the cohort. Lanreotide is an effective treatment for active acromegaly. Female sex was associated with higher rates of IGF-I normalization.

Expert consensus document: A consensus on the medical treatment of acromegaly

“…This figure is lower than those reported in previous guidelines and published papers that might have had patient selection bias due to the stringent inclusion and exclusion criteria required for clinical trials (MQ). 6,18,24 Long-term (>3 years) results on the efficacy and safety profile of SRLs are reassuring (HQ), 18,25,26 and lowering the SRL dose or decreasing the frequency of administration of SRLs might be considered for patients with long-term control of acromegaly (VLQ). 27 When reducing the SRL dose or decreasing the frequency of administration, patients should be reassessed at regular intervals to ensure maintenance of therapeutic effect (SR).…”

Hypothesis: Extra-hepatic acromegaly: a new paradigm?

“…Because of the expression of sst2 and sst5 on the somatotroph cells, pathological GH secretion can be inhibited by SA, which translates into reduced hepatic IGF1 production (31)(32)(33)(34). When this reduction is sufficient to normalize IGF1 levels, the treatment is traditionally considered adequate (31,(35)(36)(37).…”

Preparation, Characterization and Related <i>in Vivo</i> Release, Safety and Toxicity Studies of Long Acting Lanreotide Microspheres

“…While shaking, the in vivo release process of lanreotide from the microspheres was simulated under the in vitro buffered condition. Samples from the in vitro release system (20 µL) were taken at 1, 4 and 24 h as well as at 2,4,6,8,12,16,20,24,28,32,36 and 40 d and were analyzed by liquid chromatography to calculate the amount of lanreotide released at each time point using the external standard method. The liquid phase conditions were: column: C18 (GL Sciences, Inertsil ODS-2) (150 mm×4.6 mm, 5 µm); acetonitrile, hydroxide, tetramethylammonium and water as mobile phase gradient elution; detection wave length 220 nm; the peak retention time of 11 min.…”

“…The dosage in beagles was 2.67 mg/kg. Consistent with the in vitro sampling time points, blood samples were taken from the vein of the dog at 1, 4 and 24 h as well as at 2,4,6,8,12,16,20,24,28, 32, 36 and 40 d after treatment. LC-MS (API 4000 LC/MS/ MS System, Applied Biosystems, U.S.A.) was used to measure the plasma concentration of lanreotide at each time point.…”

“…7) Therefore, application of SSAs has become the treatment of choice for acromegaly, especially in patients whose tumor is large enough to obstruct the optic chiasm and impact surgical operation or in patients who have heart or lung complications, and SSAs are often used in the place of surgery. 8) Lanreotide is a somatostatin octapeptide analog with a surface disulfide bond and a non-physiological amino acid D-tryptophan in the molecular ring to increase its stability. D-β-Naphthyl alanine outside the molecular ring endows a higher selectivity.…”