Tumor Shrinkage With Lanreotide Autogel 120 mg as Primary Therapy in Acromegaly: Results of a Prospective Multicenter Clinical Trial
The Journal of Clinical Endocrinology and Metabolism (Impact Factor: 6.21). 12/2013; 99(4):jc20133318. DOI: 10.1210/jc.2013-3318
Context Methodological shortcomings often compromise investigations into the effects of primary somatostatin-analog treatment on tumor size in acromegaly. There are also limited data for the long-acting lanreotide formulation. Objective To better characterize the effects of primary lanreotide Autogel treatment on tumor size in patients with growth hormone (GH)-secreting macroadenomas. Design PRIMARYS-48-week multicenter open-label single-arm (ClinicalTrials.gov-NCT00690898; EudraCT-2007-000155-34). Setting Specialist endocrine centers. Patients Treatment-naïve acromegalic patients with GH-secreting macroadenomas. Intervention Subcutaneous lanreotide Autogel 120 mg every 28 days (without dose titration). Outcome measures Primary endpoint: null hypothesis (H0) -proportion of patients with clinically significant (≥20%) tumor volume reduction (TVR) at week 48/last post-baseline value available (LVA) is ≤55%, using central assessments from three readers. Secondary endpoints included: TVR at other time points; GH and insulin-like growth factor-1 (IGF-1); acromegalic symptoms; quality of life (QoL); safety. Results 64/90 (71.1%) patients completed the study. Clinically significant TVR at 48 weeks/LVA achieved by 62.9% [95%CI: 52.0, 72.9] of 89 patients in the primary analysis (intention-to-treat population; H0 not rejected) and 71.9-75.3% in sensitivity (n = 89) and secondary analyses (n = 63) (H0 rejected). At 12 weeks, 54.1% had clinically significant TVR. Early and sustained improvements also occurred in GH and IGF-1, acromegalic symptoms, and QoL. No patients withdrew due to gastrointestinal intolerance. Conclusions Primary treatment with lanreotide Autogel, administered at 120 mg (highest available dose) without dose titration, in patients with GH-secreting macroadenomas provides early and sustained reductions in tumor volume, GH and IGF-1, and acromegalic symptoms, and improves QoL.
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ABSTRACT: Acromegaly is a disease characterized by growth hormone (GH) excess originating, in approximately 95% of cases, from a somatotroph pituitary adenoma. Symptomatology and clinical features are due to GH and insulin-like growth factor 1 excess; unfortunately, for most patients diagnosis is delayed by several years. Acromegaly patients' morbidity and mortality are higher than those of the normal population. However, with adequate biochemical control mortality rates can be restored to normal. Tumor size and location, symptoms, comorbidities, and lastly, but not least, patient preference, are all important aspects in treatment decision making, and treatment approach should be individualized. Current therapy includes medical, surgical, and radiation. This review focuses on recent significant developments in medical therapy. There are three major therapeutic drug classes: somatostatin receptor ligands (SRLs), which represent the mainstay of medical therapy, GH receptor blockers, and dopamine agonists. Multi-ligand receptor SRLs such as pasireotide, should increase therapeutic choices for acromegaly patients currently uncontrolled on available SRLs. Furthermore, significant research has been focused in the development of novel delivery modalities (e.g., oral and long acting subcutaneous administration).
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ABSTRACT: Current guidelines do not recommend the routine use of somatostatin analogue pre-treatment prior to surgery in patients with growth hormone-secreting pituitary tumours. In theory, pre-surgical use of somatostatin analogues should improve metabolic control and reduce soft tissue swelling, leading to improved anaesthetic outcomes. Shrinkage of tumours prior to surgery might also improve surgical remission rates. Hence this article addresses the question: should all patients with acromegaly receive a somatostatin analogue prior to surgery? Clinical trials published before December 2013 were reviewed, although literature in this area remains relatively deficient.Conclusions(1) On the basis of limited data available, somatostatin analogue pre-treatment does not improve anaesthetic or immediate post-operative outcomes (i.e. hospital stay, rates of surgical complications and post-operative pituitary dysfunction). (2) Somatostatin analogues should be considered in all patients with growth hormone-secreting macroadenomas, including invasive macroadenomas, when the overall surgical remission rate for macroadenomas at the treating centre is below 50%. Four recent RCTs have demonstrated increased rates of surgical remission using such an approach. (3) When deemed appropriate, patients should be treated with somatostatin analogues for at least three months before surgery; there is currently no evidence that treatment beyond six months provides any additional benefit. Patients with minimally invasive macroadenomas are those most likely to benefit in terms of improved surgical remission.This article is protected by copyright. All rights reserved.
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ABSTRACT: Lanreotide Autogel(®) (ATG) [Somatuline(®) Autogel(®), Somatuline(®) Depot(®)] is a prolonged-release, supersaturated aqueous gel formulation of the somatostatin analogue lanreotide acetate that acts via somatostatin receptors to reduce both growth hormone and insulin-like growth factor-I levels. It is indicated for the treatment of patients with acromegaly who have had an inadequate response to or cannot be treated with surgery and/or radiotherapy. This article reviews the clinical efficacy and tolerability of lanreotide ATG in the treatment of acromegaly, as well as summarizing its pharmacological properties. Results of clinical trials and extension studies of up to 4 years duration showed that deep subcutaneous lanreotide ATG was a generally effective treatment in treatment-naive and treatment-experienced adults with acromegaly. Lanreotide ATG provided hormonal control and improved both health-related quality of life and acromegaly symptoms in most patients; it also reduced tumour volume to a clinically significant extent in studies of primary therapy. Moreover, lanreotide ATG was generally no less effective than intramuscular lanreotide long-acting microparticles and was as effective as intramuscular octreotide long-acting release in switching or crossover studies, including those with standard or extended dosing intervals. Lanreotide ATG is generally well tolerated; the most frequently reported adverse events were mild or moderate transient gastrointestinal symptoms. Lanreotide ATG also has the advantage of being available in a convenient pre-filled syringe and is given subcutaneously rather than intramuscularly. Thus, lanreotide ATG continues to be a valuable option in the treatment of acromegaly, with potential advantages being ease of administration and longer dosing intervals in patients who have an adequate response to initial therapy.
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