Tumor Shrinkage With Lanreotide Autogel 120 mg as Primary Therapy in Acromegaly: Results of a Prospective Multicenter Clinical Trial
ABSTRACT 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: The presence/persistence of microorganisms in the pulp and periapical area corresponds to the maintenance of an exacerbated immune response that leads to the start of periradicular bone resorption and its perpetuation. In endodontic treatment, the available intracanal medications do not have all the desirable properties in the context of endodontic infection and apical periodontitis; they need to include not only strong antimicrobial performance but also an immunomodulatory and reparative activity, without host damage. In addition, there are various levels of resistance to root canal medications. Thus, antimicrobial agents that effectively eliminate resistant species in root canals could potentially improve endodontic treatment. In the emergence of new therapies, an increasing number of studies on antimicrobial peptides (AMPs) have been seen over the past few years. AMPs are defense biomolecules produced in response to infection, and they have a wide spectrum of action against many oral microorganisms. There are some studies that correlate peptides and oral infections, including oral peptides, neuropeptides, and bacterial, fish, bovine and synthetic peptides. So far, there are around 120 published studies correlating endodontic microbiota with AMPs but, according to our knowledge, there are no registered patents in the American patent database. There are a considerable number of AMPs that exhibit excellent antimicrobial activity against endodontic microbiota at a small inhibitory concentration and modulate an exacerbated immune response, down-regulating bone resorption. All these reasons indicate the antimicrobial peptide-based endodontic treatment as an emerging and promising option.Biotechnology Advances 11/2014; 33(1). DOI:10.1016/j.biotechadv.2014.10.013 · 8.91 Impact Factor
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ABSTRACT: Patients with acromegaly usually harbor macroadenomas measuring between 10-30 mm in maximal diameter. Giant (adenoma size > 40 mm) growth hormone (GH)-secreting pituitary tumors are rarely encountered. We have identified 34 patients (15 men, 19 females) with giant adenomas among 762 subjects (4.5%) with acromegaly in our records, and characterized their clinical characteristics and response to treatment. Mean age at diagnosis was 34.9+12.5 years (range, 16-67 years). Mean adenoma size 49.4+9.4 mm (range, 40-80 mm); 30 adenomas showed cavernous sinus invasion and 32 had suprasellar extension. Twenty-nine (85%) had visual fields damage. Mean baseline IGF-1 was 3.4+1.8 x ULN. All patients beside one underwent pituitary surgery (1-3 procedures) but none achieved hormonal remission following 1st surgery. Among the 28 subjects with visual disturbances, 14 recovered post-operatively and 13 improved. Treatment with somatostatin analogues was given to all patients after surgical failure. Six achieved remission, nine others were partially controlled (IGF-1< 1.5 x ULN; 3/9 when combined with cabergoline), and 17 did not respond (two were lost). Nine patients were treated with pegvisomant, alone (n=4), or combined with somatostatin analogs (n=5); five are in remission, two are partially controlled. Pasireotide-LAR achieved hormonal remission in one of 6 patients. Currently, after a mean follow-up of 8.9 years, 17 patients are in biochemical remission, 8 are partially controlled, and 7 are uncontrolled (two not in follow-up). Giant GH-adenomas are invasive, uncontrolled by surgery, and respond poorly to medical treatment. Aggressive multimodal therapy is critical for their management, enhancing control rate and biochemical remission.European Journal of Endocrinology 03/2015; 172(6). DOI:10.1530/EJE-14-1117 · 3.69 Impact Factor
Article: Pegvisomant treatment in Acromegaly[Show abstract] [Hide abstract]
ABSTRACT: Historically medical treatment of acromegaly has mainly used as adjuvant after surgery. In the last decades, an increase range of medical therapy options was available. Somatostatin analogues became the cornerstone of medical treatment in acromegaly and are even seen as primary treatment in a selected group of acromegaly subjects. The most recent medical treatment available for acromegaly patients is pegvisomant, a growth hormone receptor antagonist. To date it is the most effective medical treatment, but it is costly. Pegvisomant is used as monotherapy and combined with somatostatin analogues. In this article we review clinical studies and cohorts that have documented the efficacy of pegvisomant monotherapy and combined and give a concise view on side effects. © 2015 S. Karger AG, Basel.Neuroendocrinology 03/2015; DOI:10.1159/000381644 · 4.93 Impact Factor