scholarly journals A comparison between octreotide-LAR and lanreotide-SR in the chronic treatment of acromegaly

1999 ◽  
pp. 267-271 ◽  
Author(s):  
R Cozzi ◽  
D Dallabonzana ◽  
R Attanasio ◽  
M Barausse ◽  
G Oppizzi
Keyword(s):  
Chronic Treatment ◽  
Somatostatin Analogs ◽  
Somatostatin Analog ◽  
Normal Range ◽  
First Line ◽  
Hormonal Change ◽  
Upper Limit ◽  
Igf I ◽  
Long Acting ◽  
Active Disease

BACKGROUND: At present long-acting somatostatin analogs represent the first-line medical treatment of acromegaly. These drugs produce stable suppression of GH in most sensitive patients and IGF-I normalization in many; they also increase the compliance of acromegalic patients. The recent availability of octreotide (OC)-LAR, a somatostatin analog to be administered at 28-day intervals, has prompted us to compare, in the same group of patients, its effects and those of another somatostatin analog already available, lanreotide-SR (LSR, to be administered at 14-day intervals). PATIENTS: Twelve somatostatin analog-sensitive acromegalic patients with active disease were enrolled in a prospective open sequential study after giving their informed consent. After chronic treatment with LSR (6-24 months), the patients were changed to treatment with OC-LAR, without wash-out. LSR had been administered at individually tailored dosages (30 mg i.m. at 7-21-day intervals, median 10 days - every 7 days in seven patients, 10 days in two patients, 14 days in two patients and 21 days in one patient) according to GH and IGF-I responses. Disease stability was obtained, as shown by maximal GH/IGF-I suppression without any significant hormonal change between the last two control measurements. OC-LAR was administered i.m. at 28-day intervals six times at the dosage of 20 mg for the first three times and 10 or 30 mg for the last three times (according to individual GH/IGF-I responses). GH (mean of three, hourly samples) and IGF-I concentrations were evaluated on the same day as each administration of the drug, before its injection. RESULTS: GH and IGF-I values were significantly decreased by LSR treatment. GH decreased from 41.6 +/- 14.6 microg/l (mean +/- s.e.) to 7.2 +/- 1.5 microg/l (P < 0.02), whereas IGF-I values declined from 959 +/- 95 microg/l to 460 +/- 61 microg/l (P < 0.00001), expressed as absolute values, and from 287 +/- 30% to 137 +/- 19% expressed as percentage of the upper limit of normal range (% ULNR). At the end of the last cycle, OC-LAR treatment achieved a significant further suppression both in GH (to 5.1 +/- 1.1 microg/l, P < 0.05 compared with LSR) and in IGF-I concentrations (to 374 +/- 60 microg/l, P<0.05 compared with LSR, and to 112 +/- 19% as % ULNR). LSR decreased GH concentrations to less than 2.5 microg/l in one patient and normalized IGF-I concentrations in four patients. OC-LAR decreased GH concentrations to less than 2.5 microg/l in four patients and normalized or near-normalized IGF-I concentrations (i.e. to < 110% ULNR) in eight patients. CONCLUSIONS: These preliminary results show that the once-monthly OC-LAR administration schedule proved more efficacious than LSR given every 7-21 days, in a greater number of acromegalic patients.

scholarly journals Acromegaly: recent progress in diagnostics and treatment

2011 ◽  
Vol 57 (1) ◽  
pp. 46-59 ◽  
Author(s):  
N N Molitvoslovova
Keyword(s):  
Recent Progress ◽  
New Technologies ◽  
Somatostatin Analogs ◽  
Normal Range ◽  
Gh Receptor ◽  
Modern Methods ◽  
Igf I ◽  
Gh Receptor Antagonist ◽  
Serious Disease ◽  
Long Acting

Acromegaly is a serious disease with different complications leads to reduced life expectancy and increase mortality. Only early diagnosis and modern methods of management of disease lead to remission. According to consensus on criteria for cure of acromegaly (2010) the measurement of GH and age-matched total IGF-I concentrations are the most important biochemical variables for the diagnosis of acromegaly and for monitoring progression or treatment response. The optimal disease control is now defined as IGF-I level in the age – adjusted normal range, random GH levels less than 1,0 µg/liter and nadir GH level during OGTT less than 0,4 µg/liter. MRI with use a contract substance is the best method of adenoma visualization. The trassphenoidal surgery with new technologies (endoscope, intraoperative blood sampling, neuronavigation, intraoperative MRI), radiosurgery, modern medical treatment (multiligand long-acting somatostatin analogs, GH receptor antagonist) are effective modalities for treatment of acromegaly, which elaborated last decades.

scholarly journals What is the efficacy of switching to weekly pegvisomant in acromegaly patients well controlled on combination therapy?

2016 ◽  
Vol 174 (5) ◽  
pp. 663-667 ◽  
Author(s):  
A Muhammad ◽  
A J van der Lely ◽  
R D O’Connor ◽  
P J Delhanty ◽  
J Dal ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Baseline Level ◽  
Somatostatin Analogs ◽  
High Dose ◽  
Normal Range ◽  
Open Label ◽  
Upper Limit ◽  
Long Acting ◽  
Viable Treatment

Abstract Context Although combination therapy of acromegaly with long-acting somatostatin analogs (LA-SSAs) and pegvisomant (PEGV) normalizes insulin-like growth factor-1 (IGF1) levels in the majority of patients, it requires long-term adherence. Switching from combination therapy to monotherapy with weekly PEGV could improve patients’ comfort, but the efficacy is unknown. Objective To assess the efficacy of switching to PEGV monotherapy in patients well controlled on combination therapy of LA-SSAs and PEGV. Design Single-center, open-label observational pilot study. LA-SSA therapy was discontinued at baseline and all patients were switched to PEGV monotherapy for 12 months. If IGF1 levels exceeded 1.0 times upper limit of normal (ULN), PEGV dose was increased by 20 mg weekly. Subjects and methods The study included 15 subjects (eight males), with a median age of 58 years (range 35 – 80) on combination therapy of high-dose LA-SSAs and weekly PEGV for >6 months, and IGF1 levels within the normal range. Treatment efficacy was assessed by measuring serum IGF1 levels. Results After 12 months of weekly PEGV monotherapy, serum IGF1 levels of 73% of the subjects remained controlled. In one patient, LA-SSA had to be restarted due to recurrence of headache. IGF1 levels increased from a baseline level of 0.62 × ULN (range 0.30 – 0.84) to 0.83 × ULN (0.30 – 1.75) after 12 months, while the median weekly PEGV dose increased from 60 (30 – 80) mg to 80 (50 – 120) mg. Conclusion Our results suggest that switching from combination therapy of LA-SSAs and PEGV to PEGV monotherapy can be a viable treatment option for acromegaly patients without compromising efficacy.

Treatment of invasive growth hormone pituitary adenomas with long-acting somatostatin analog SMS 201–995 before transsphenoidal surgery

1994 ◽  
Vol 81 (1) ◽  
pp. 10-14 ◽  
Author(s):  
Tomás Lucas-Morante ◽  
José García-Uría ◽  
Javier Estrada ◽  
Gertrudis Saucedo ◽  
Ana Cabello ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Transsphenoidal Surgery ◽  
Somatostatin Analog ◽  
Clinical Activity ◽  
Tumor Shrinkage ◽  
Content Type ◽  
Gh Secretion ◽  
Igf I ◽  
Long Acting ◽  
Fine Print

✓ The purpose of this study was to determine whether the long-acting somatostatin analog SMS 201–995 (octreotide) shrinks growth hormone (GH)-secreting adenomas and improves the results of subsequent transsphenoidal surgery. Ten previously untreated active acromegalic patients (nine women and one man) with invasive tumors were treated with SMS 201–995 (100 µg subcutaneously every 8 hours) for 6 weeks prior to transsphenoidal surgery. The clinical activity, mean GH secretion, insulin-like growth factor (IGF)-I concentration, and tumor volume were measured under basal conditions and on Days 14, 28, and 42 of treatment. The SMS 201–995 improved the symptoms of acromegaly in all patients. Mean levels of both GH and IGF-I (± standard deviation) were significantly decreased by Day 14 (from 92.9 ± 30.5 to 44.9 ± 20.3 µg/liter and from 10.6 ± 7.4 to 5.9 ± 2.6 U/ml, respectively), after which there were only slight further decreases. Six (60%) of the 10 patients experienced tumor shrinkage ranging from 9% to 78% (mean 30%). When it occurred, tumor shrinkage was significant by Day 14 (7.9 ± 6.3 to 6.5 ± 5.1 cu cm) and no further shrinkage was achieved by longer administration. Transsphenoidal surgery reduced postoperative GH levels to less than 2 µg/liter and IGF-I to less than 1.5 U/ml in six patients (60%). This percentage of cure is higher than expected from the literature and the authors' previous experience. However, an investigation of the influence of this drug on several parameters, such as reduction of tumor size or GH and IGF-I concentrations, has failed to prove any relationship. Only pretreatment size of the tumor was of predictive value with respect to the surgical outcome.

scholarly journals Efficacy and tolerability of lanreotide Autogel therapy in acromegalic patients previously treated with octreotide LAR

2004 ◽  
pp. 317-324 ◽  
Author(s):  
O Alexopoulou ◽  
P Abrams ◽  
J Verhelst ◽  
K Poppe ◽  
B Velkeniers ◽  
...  
Keyword(s):  
Side Effects ◽  
Fixed Dose ◽  
Normal Range ◽  
Open Label ◽  
Technical Problems ◽  
Octreotide Lar ◽  
Igf I ◽  
Long Acting ◽  
Local Side ◽  
Lanreotide Autogel

OBJECTIVE: This open label, multicentre study was designed to evaluate the efficacy and tolerability of lanreotide Autogel (L-Autogel) in acromegalic patients over a 24-week period. The outcome of treatment with this new, long-acting, aqueous formulation of lanreotide was also compared with the patients' previous treatment with octreotide long acting repeatable (LAR). DESIGN AND METHODS: Twenty-five acromegalic patients (13 males, mean age 51+/-12 years) were switched from octreotide LAR (20-40 mg/4 weeks for at least 6 months) to L-Autogel, given deep subcutaneously at a fixed dose of 90 mg/4 weeks. After 12 weeks, the dose of L-Autogel was titrated according to patients' mean GH and IGF-I levels at week 8. It was increased to 120 mg/4 weeks if GH>2.5 microg/l or if IGF-I was above the age-adjusted normal range. It was reduced to 60 mg/4 weeks if mean GH<1 microg/l and IGF-I was within the normal range. If the values did not fall within these ranges, the dose remained unchanged at 90 mg. RESULTS: After 24 weeks of treatment with L-Autogel (final doses 60 mg in 3 patients, 90 mg in 4 patients and 120 mg in 18 patients), mean serum GH (2.9+/-2.4 microg/l) and IGF-I concentrations (332+/-193 microg/l) remained statistically unchanged when compared with baseline values under octreotide LAR (GH 2.4+/-1.8 microg/l and IGF-I 337+/-201 microg/l, non significant (NS)). There was a significant improvement of the acromegalic symptom score over the study period, from 4.8+/-3.4 to 2.8+/-2.5 (P<0.001) and a small but significant reduction in the residual pituitary tumour volume (P<0.05). Local side-effects were observed less frequently and no technical problems were encountered with the L-Autogel injections, as opposed to treatment with octreotide LAR (60 difficult injections/150 (P<0.001)). CONCLUSIONS: L-Autogel appears to be as effective as octreotide LAR in lowering GH and IGF-I concentrations in acromegalic patients. This treatment was also well tolerated by the patients, giving fewer local side-effects and technical problems with injections. These advantages may improve the long-term acceptability of medical treatment in acromegaly.

scholarly journals MON-297 Withdrawal from Long-Acting Somatostatin Receptor Ligand Injections in Adult Patients with Acromegaly: Results from the Phase 3, Randomized, Double-Blind, Placebo-Controlled CHIASMA OPTIMAL Study

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Lisa B Nachtigall ◽  
Susan Leanne Samson ◽  
Maria Fleseriu ◽  
Marek Bolanowski ◽  
William Henry Ludlam ◽  
...  
Keyword(s):  
Placebo Group ◽  
Somatostatin Receptor ◽  
Adult Patients ◽  
Open Label ◽  
Phase 3 ◽  
Igf I ◽  
Open Label Extension ◽  
Long Acting ◽  
Somatostatin Receptor Ligand ◽  
Active Disease

Abstract Data on the impact of withdrawal from long-acting somatostatin receptor ligand (SRL) injections on disease activity in patients with acromegaly are limited. The phase 3 Octreotide capsules versus Placebo Treatment In MultinationAL centers (OPTIMAL) study assessed the efficacy and safety of oral octreotide capsules in adult patients with acromegaly responding to injectable SRL therapy. The placebo-controlled arm of this study allowed for assessment of acromegaly biochemical and disease activity in patients after withdrawal from SRL treatment. A multinational, randomized, placebo-controlled study was conducted in 56 adult patients with active acromegaly. Patients were ≥ 18 years of age, had evidence of active disease (defined as IGF-I ≥1.3 x ULN after last pituitary surgery), and an average IGF-I ≤ 1.0 x ULN in response to a stable dose of SRL injection. Patients were randomized, 1 month following their last injection, to octreotide capsule or placebo for 36 weeks, with an option to enroll in an open-label extension. The primary aim was to determine the proportion of patients maintaining biochemical response, defined as IGF-I ≤1.0 x ULN (average of week 34 and 36). The trial met the primary endpoint, with 58% (16/28) of patients receiving octreotide capsules maintaining IGF-I response vs 19% (5/28) receiving placebo (P=0.008). The median time to loss of response (2 criteria evaluated: IGF-I &gt;1.0 and ≥ 1.3 x ULN for 2 consecutive visits) was 16 weeks in the placebo group, while it was not reached in the octreotide capsule group. Of the 5 patients in the placebo group who maintained their biochemical response at 36 weeks, only 2 (7% of placebo group) did not meet loss of response criteria. When IGF-I values for any 2 consecutive visits were analyzed for patients receiving placebo, 93% (26/28) lost response based on IGF-I &gt; 1 x ULN and 79% (22/28) lost response based on IGF-I ≥ 1.3 x ULN. Irrespective of biochemical control of acromegaly, 26/28 patients receiving placebo experienced active disease-related symptoms reported as AEs of special interest (AESIs). Most common AESIs (≥ 5%) included arthralgia/arthritis (60.7%), soft tissue swelling (35.7%), headache (32.1%), hyperhidrosis (25%), carpal tunnel (14.3%), musculoskeletal pain (14.3%), weight increased (7.1%) and tongue disorders (7.1%). The 5 patients receiving placebo with controlled IGF-I at 36 weeks received active medical treatment in the open label extension by decision of their study PIs, as they were deemed to have either lost their response during the study or had continuing active acromegaly symptoms. 93% of patients receiving placebo lost response following withdrawal of injectable SRLs, with a median duration of 16 weeks. All 5 patients receiving placebo who met the primary endpoint criteria at the end of the study were assessed clinically to have active disease and were continued on oral SRL treatment in the open label extension.

scholarly journals Place of Cabergoline in Acromegaly: A Meta-Analysis

2011 ◽  
Vol 96 (5) ◽  
pp. 1327-1335 ◽  
Author(s):  
Laure Sandret ◽  
Patrick Maison ◽  
Philippe Chanson
Keyword(s):  
Treatment Duration ◽  
Meta Analysis ◽  
Single Agent ◽  
Somatostatin Analogs ◽  
Somatostatin Analog ◽  
Individual Data ◽  
Duration Of Treatment ◽  
Single Agent Therapy ◽  
Accurate Picture ◽  
Igf I

Context: Cabergoline is widely considered to be poorly effective in acromegaly. Objective: The aim of this study was to obtain a more accurate picture of the efficacy of cabergoline in acromegaly, both alone and in combination with somatostatin analogs. Design: We systematically reviewed all trials of cabergoline therapy for acromegaly published up to 2009 in four databases (PubMed, Pascal, Embase, and Google Scholar). We identified 15 studies (11 prospective) with a total of 237 patients; none were randomized or placebo-controlled. A meta-analysis was conducted on individual data (n = 227). Results: Cabergoline was used alone in nine studies. Fifty-one (34%) of the 149 patients achieved normal IGF-I levels. In multivariate analysis, the decline in IGF-I was related to the baseline IGF-I concentration (β = 1.16; P &lt;0.001), treatment duration (β = 0.28; P &lt; 0.001), and baseline prolactin concentration (β = −0.18; P = 0.01), and with a trend toward a relation with the cabergoline dose (β = 0.38; P =0.07). In five studies, cabergoline was added to ongoing somatostatin analog treatment that had failed to normalize IGF-I. Forty patients (52%) achieved normal IGF-I levels. The change in IGF-I was significantly related to the baseline IGF-I level (β = 0.74; P &lt; 0.001) but not to the dose of cabergoline, the duration of treatment, or the baseline prolactin concentration. Conclusion: This meta-analysis suggests that cabergoline single-agent therapy normalizes IGF-I levels in one third of patients with acromegaly. When a somatostatin analog fails to control acromegaly, cabergoline adjunction normalizes IGF-I in about 50% of cases. This effect may occur even in patients with normoprolactinemia.

scholarly journals MON-288 TSH Deficiency in Patients on Somatostatin Analog for TSH-PitNET

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Frederic Illouz ◽  
Philippe Chanson ◽  
Emmanuel D Sonnet ◽  
Thierry Christian Brue ◽  
Amandine Ferriere ◽  
...  
Keyword(s):  
Somatostatin Analogs ◽  
Inclusion Criteria ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Tumor Reduction ◽  
Central Hyperthyroidism ◽  
Third Line ◽  
Long Acting ◽  
Tsh Deficiency

Abstract Background: Somatostatin analogs (SSA) are efficiently used to control central hyperthyroidism in patients with thyrotropin-secreting pituitary neuroendocrine tumor (TSH-PitNET). The aim of this study was to describe the frequency of thyrotropin (TSH) deficiency under SSA in patients with TSH-PitNET. Methods: We retrospectively recruited patients presenting a central hyperthyroidism due to TSH-PitNET. Inclusion criteria were patients treated in first, second or third line by short or long-acting SSA, with central hyperthyroidism before SSA. Patients treated by radiotherapy or dopamine agonist were excluded. TSH deficiency was defined by either a low FT4 or low FT4 and FT3, associated with non-elevated TSH concentrations during SSA therapy. We analyzed the frequency of TSH deficiency and the characteristics of patients with or without TSH deficiency. Results: 46 patients were included in the study. SSA were used as the first-line therapy in 21 of 46 patients (46%). Central hyperthyroidism was controlled in 36 of 46 patients (78%). TSH deficiency appeared in 7 of 46 patients (15%), after a median time of 4 weeks (4–7) after the starting of SSA, and for a median duration of 3 months (2.5–3). The TSH deficiency occurred after 1 to 3 injections of long-acting SSA. There were no differences in terms of clinical and hormonal features and size of adenomas between patients with or without TSH deficiency. Conclusions: In patients with central hyperthyroidism due to TSH-PitNET, SSA can induce TSH deficiency. Thyrotropic function should be assessed before each injection of SSA in order to adapt the frequency of injection when control of thyrotoxicosis rather than tumor reduction is purpose of the treatment.

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