Control of IGF-I levels with titrated dosing of lanreotide Autogel over 48weeks in patients with acromegaly (original) (raw)
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Clinical Endocrinology, 2007
Background Somatostatin analogues have been used successfully for the treatment of acromegaly but no randomized studies have compared the effects of lanreotide Autogel (LAN) and octreotide acetate long-acting repeatable (OCT). Objective To compare the effect of LAN and OCT for the treatment of acromegaly in a randomized study design. Material and methods Twelve acromegalic patients were included and 10 patients completed treatment with LAN or OCT for 6 months and were then switched to the opposite treatment modality for 6 months without a washout period in a randomized crossover design. GH and IGF-I profiles, clinical and biochemical evaluations were performed at 0, 4, 6, 10 and 12 months. Results After 6 months of treatment, five patients had GH levels < 0·38 μ g/l during both therapies. The remaining patients had GH levels > 0·38 μ g/l during both LAN and OCT treatment. Four patients had normalized IGF-I levels during both treatment regimes. Two patients on LAN and one on OCT had normalized IGF-I levels during one treatment and not during the other. In three patients, IGF-I levels were elevated during both therapies. Four patients developed palpable nodules, two patients on LAN and two patients on OCT. Gastrointestinal complaints were seen in three patients during both therapies, in three patients only during LAN, and in one patient only during OCT. Two patients were withdrawn from the study because of serious adverse effects during LAN. After the study period, four patients preferred LAN and six patients preferred OCT treatment. Conclusion The effects of LAN and OCT therapy on GH and IGF-I levels were comparable, but 3/10 patients had different treatment efficacies and 6/10 had different side-effect profiles during the LAN and OCT treatment. These results indicate that a change from LAN to OCT or vice versa may be beneficial in some patients with treatment failure or side-effects.
European Journal of Endocrinology, 2010
ObjectiveTo evaluate the efficacy and safety of coadministered lanreotide Autogel (LA; 120 mg/month) and pegvisomant (40–120 mg/week) in acromegaly.DesignThis is a 28-week, multicenter, open-label, single-arm sequential study.MethodsPatients (n=92) biochemically uncontrolled, on somatostatin analogs (SSAs) or using pegvisomant monotherapy entered a 4-month run-in taking LA (120 mg/month). Patients uncontrolled after the run-in period (n=57) entered a 28-week coadministration period, receiving LA 120 mg/month plus pegvisomant (60 mg once weekly, adapted every 8 weeks based on IGF1 levels to 40–80 mg once weekly or 40 or 60 mg twice weekly).ResultsIn total, 33 (57.9%) patients had normalized IGF1 following coadministration (P<0.0001 versus 30% minimum clinically relevant); median pegvisomant dose in normalized patients was 60 mg/week. IGF1 normalized at any time during coadministration in 45 (78.9%) patients (P<0.0001) with median pegvisomant dose at 60 mg/week. Being nondiabeti...
European Journal of Endocrinology, 2018
Context Discordant GH and IGF-I values are frequent in acromegaly. The clinical significance and its dependence on treatment modality and of glucose-suppressed GH (GHnadir) measurements remain uncertain. Objective To evaluate the effects of targeting either IGF-I or GH during somatostatin analogue (SA) treatment. Patients and Methods 84 patients with controlled acromegaly after surgery (n = 23) or SA (n = 61) underwent a GH profile including an OGTT, at baseline and after 12 months. SA patients were randomized to monitoring according to either IGF-I (n = 33) or GHnadir (n = 28). SA dose escalation was allowed at baseline and 6 months. Main outcome measures GHnadir and IGF-I at baseline and 12 months, and disease-specific Quality of Life (QoL). Results IGF-I and fasting GH levels were comparable between the surgery and the SA group, whereas GHnadir (µg/L) was lower in the surgery group (GHnadir 0.7 ± 0.1 vs 0.3 ± 0.1, P < 0.01). SA dose increase was performed in 20 patients in the...
Pituitary, 2018
Purpose In clinical research involving acromegalic patients naïve to somatostatin-receptor ligands (SRLs), 19 and 31% of those receiving the SRLs octreotide LAR and pasireotide LAR, respectively, achieved GH < 2.5 ng/mL + normalized IGF-1 concentrations. The proportions achieving control appeared higher in the post-surgery compared with the de-novo setting with pasireotide, but more similar with octreotide. Using pooled data from multicenter clinical trials, we examined the biochemical efficacy of lanreotide depot/Autogel in similar settings. Methods Inclusion criteria: Ipsen-sponsored, 48-52-week trials in SRL-naïve acromegalic populations receiving lanreotide depot (60-120 mg); patients were included if de novo (no prior acromegaly treatment) or post-surgery (no medical treatment; radiotherapy allowed unless within previous 3 years). Efficacy endpoints included normalized IGF-1 levels and GH < 2.5 ng/mL + normalized IGF-1 at study end/last value available. Analyses: all patients (analysis #1) and subset with baseline GH > 5 ng/mL (analysis #2). Results Three studies were included. Analysis #1: normalized IGF-1 was achieved by 42% (71/171) of patients overall (postsurgery, 46% [21/46]; de-novo, 40% [50/125]); GH < 2.5 ng/mL + normalized IGF-1 was achieved by 35% (59/171) (39% [18/46] and 33% [41/125], respectively). Analysis #2: normalized IGF-1 levels, 39% (46/118) (post-surgery, 40% [10/25]; de-novo, 39% [36/93]); GH < 2.5 ng/mL + normalized IGF-1, 31% (36/118) (28% [7/25] and 31% [29/93], respectively). Conclusion In these pooled analyses of SRL-naïve patients receiving lanreotide depot, 39-42% achieved IGF-1 control and 31-35% achieved GH and IGF-1 control. Control rates within post-surgery cohorts did not differ markedly from those in corresponding de-novo cohorts.
The Journal of clinical endocrinology and metabolism, 2014
Treatment for acromegaly patients with long-acting somatotropin release-inhibiting factor (LA-SRIF) often does not result in complete normalization of IGF-1. Addition of pegvisomant (PEGV), a GH receptor antagonist, could improve this; however, the literature has not described long-term follow-up. To assess long-term efficacy and safety of this combined treatment in the largest current single-center cohort of patients, from 2004-2013. Acromegaly patients were treated for at least 6 months with a high-dose LA-SRIF. To patients with persistently elevated IGF-1 levels (>1.2 × upper limit of normal) or poor quality of life, PEGV was added as one weekly injection. The patients (n = 141) were treated with PEGV and LA-SRIFs for a median period of 4.9 years (range, 0.5-9.2). Efficacy, defined as the lowest measured IGF-1 level during treatment, was 97.0%. The median PEGV dose to achieve this efficacy was 80 mg weekly (interquartile range, 60-120 mg). Combination treatment-related adverse...
Therapeutic options in the management of acromegaly: focus on lanreotide Autogel®
Biologics: Targets & Therapy, 2008
Background: In acromegaly, expert surgery is curative in only about 60% of patients. Postoperative radiation therapy is associated with a high incidence of hypopituitarism and its effect on growth hormone (GH) production is slow, so that adjuvant medical treatment becomes of importance in the management of many patients. Objective: To delineate the role of lanreotide in the treatment of acromegaly. Methods: Search of Medline, Embase, and Web of Science databases for clinical studies of lanreotide in acromegaly. Results: Treatment with lanreotide slow release and lanreotide Autogel ® normalized GH and insulin-like growth factor-I (IGF-I) concentrations in about 50% of patients. The effi cacy of 120 mg lanreotide Autogel ® on GH and IGF-I levels was comparable with that of 20 mg octreotide LAR. There were no differences in improvement of cardiac function, decrease in pancreatic β-cell function, or occurrence of side effects, including cholelithiasis, between octreotide LAR and lanreotide Autogel ® . When postoperative treatment with somatostatin analogs does not result in normalization of serum IGF-I and GH levels after noncurative surgery, pegvisomant alone or in combination with somatostatin analogs can control these levels in a substantial number of patients.
The Journal of Clinical Endocrinology & Metabolism, 2003
tive open multicenter study to 92 patients with active acromegaly (61 women and 31 men, aged 20 -79 yr). LAN60 was given as adjuvant treatment (AT) in 62 patients; the other 30 patients [primary treatment (PT)] were de novo (n ؍ 20) or previously treated only by pharmacotherapy (n ؍ 10). After wash-out from previous treatments, LAN60 was started im every 28 d for 3 injections; the dose was then individually tailored, aiming at lowering GH to less than 2.5 g/liter and IGF-I to the normal range. After a median follow-up of 24 months (range, 6 -48 months), IGF-I normalized in 65% of patients, decreasing from 199 ؎ 8% (expressed as a percentage of the upper limit of normal range; mean ؎ SE) to 87 ؎ 4% (P < 0.0001). GH fell to less than 2.5 g/liter in 63% of patients and to less than 1 g/liter in 25%, decreasing from 20 ؎ 3 to 3 ؎ 0.4 g/liter (P < 0.0001). A progressive increase in the rate of IGF-I Ninety-two acromegalic patients (61 women and 31 men; aged 20 -79 yr; median, 50 yr), attending 5 different centers in Italy, entered this prospective open study. Inclusion criteria were active disease (according to the clinical picture, GH levels not suppressible to Ͻ1 g/liter after an oral glucose load and elevated age-adjusted IGF-I levels) and sensitivity Abbreviations: AT, Adjuvant treatment; HDL, high density lipoprotein; LAN, lanreotide; LAN30, lanreotide 30 mg; LAN60, lanreotide 60 mg; NS, neurosurgery; OC, octreotide; OC-LAR, octreotide long-acting repeatable; PT, primary treatment; RT, radiotherapy; SA, somatostatin analogs; ULNR, upper limit of normal range.
Effectiveness of lanreotide autogel 120 mg at extended dosing intervals for acromegaly
Endocrine
Purpose Recent data indicate that extended dosing intervals (EDIs) with lanreotide autogel 120 mg are effective and well-received among patients with acromegaly who have achieved biochemical control with monthly injections of long-acting somatostatin analogues (SSAs). We further evaluated the effectiveness of lanreotide autogel 120 mg delivered at EDIs (>4 weeks) in routine clinical practice. Methods Cross-sectional, multicentre, observational study conducted to determine the effectiveness—measured by control of serum insulin-like growth factor 1 (IGF-1)—of lanreotide autogel 120 mg at dosing intervals >4 weeks for ≥6 months in selected patients with acromegaly treated in routine clinical practice (NCT02807233). Secondary assessments included control of growth hormone (GH) levels, treatment adherence, patient satisfaction, and quality of life (QoL) using validated questionnaires (EQ-5D, AcroQoL, and TSQM-9). Patients who received radiotherapy within the last 6 months were excl...