TITLE

A Canadian multi-centre, open-label long-term study of Pegvisomant treatment in refractory acromegaly

AUTHOR(S)
Ezzat, Shereen; Gaspo, Rania; Serri, Omar; Ur, Ehud; Chik, Constance L.
PUB. DATE
December 2009
SOURCE
Clinical & Investigative Medicine;Dec2009, Vol. 32 Issue 6, pE265
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Purpose: Acromegaly is a rarely diagnosed condition with potentially serious complications including accelerated heart disease and reduced survival. After a mean interval of nearly 9 years from onset of disease, a significant proportion of patients are diagnosed with invasive adenomas precluding complete surgical resection. Furthermore, strict normalization of the growth hormone (GH) target insulinlike growth factor I (IGF-I) cannot always be achieved by adjunctive medical therapy with somatostatin analogues. Here we report the results of a Canadian multi-centre study open-label, dose-titrated long-term study examining safety and efficacy outcomes of a growth hormone receptor antagonist, pegvisomant in 19 patients with refractory acromegaly. Methods: Previously pegvisomant-treated and treatment naïve refractory acromegalic patients at least 18 yr of age were eligible (n=19). Patients received open-label daily subcutaneous injections of pegvisomant adjusted according to IGF-I levels. Safety and IGF-I levels were assessed every 4 to 6 wk. Baseline and follow-up visits at 3-month intervals also included administration of the Signs and Symptoms of Acromegaly uestionnaire. This study is registered with ClinicalTrials.gov, NCT00151437. Results: We show that, in escalating doses, pegvisomant results in age-adjusted normalization of IGF-I in nearly all such patients. This IGF-I normalization occurred early on and was maintained throughout the study period of 27 months (IGF-I standard deviation score (SDS), mean ± SE: 1.66 ± 0.36, P=0.0003 vs baseline), with a nadir at 18 months (IGF-I SDS, mean ± SE: 1.50 ± 0.38, P=0.0010 vs baseline). IGF-I control was also accompanied by measurable improvements in disease-associated symptoms and without radiographic evidence of pituitary tumour progression. Overall, the safety profile of pegvisomant therapy in this patient population was found to be satisfactory and suitable for a long-term treatment. Conclusion: Our findings provide support for the longterm safety and efficacy of the GH receptor antagonist pegvisomant in achieving IGF-I control in patients with refractory acromegaly.
ACCESSION #
47781874

 

Related Articles

  • Novel Somatostatin Analogs. James, Andy // Current Medical Literature: GH & Growth Factors;2004, Vol. 19 Issue 2, p29 

    Discusses novel somatostatin analogs. History on the discovery and therapeutic application of the peptide; Therapeutic roles of the somatostatin receptors based on cell type; Potency of octa- and hexapeptides in treating acromegaly, lowering growth hormones and causing tumor involutions;...

  • Somatostatin Receptor Expression in GH-Secreting Pituitary Adenomas Treated with Long-Acting Somatostatin Analogues in Combination with Pegvisomant. Franck, Sanne E.; Gatto, Federico; van der Lely, aart Jan; Janssen, Joseph a.M.J.L.; Dallenga, alof H.G.; Nagtegaal, a. Paul; Hofland, Leo J.; Neggers, Sebastian J.C.M.M. // Neuroendocrinology;Jun2017, Vol. 105 Issue 1, p44 

    Background: Growth hormone-secreting pituitary adenomas (somatotroph adenoma) predominantly express somatostatin receptors (SSTRs) subtypes 2 and 5. Higher SSTR2 expression on somatotroph adenomas results in a better response to somatostatin analogues (SSAs), which preferentially bind, but also...

  • Homologous Upregulation of sst2 Somatostatin Receptor Expression in the Rat Arcuate Nucleus in vivo. Tannenbaum, Gloria S.; Turner, Joel; Fang Guo, Joel; Videau, Catherine; Epelbaum, Jacques; Beaudet, Alain // Neuroendocrinology;2001, Vol. 74 Issue 1, p33 

    In vitro studies using various cell systems have provided conflicting results regarding homologous regulation of somatostatin (SRIH) receptors, and information on whether SRIH regulates the expression of its own receptors in vivo is lacking. In the present study we examined, by in situ...

  • Pathology of Acromegaly. Horvath, Eva; Kovacs, Kalman // Neuroendocrinology;2006, Vol. 83 Issue 3/4, p161 

    This review summarizes current knowledge on pituitary changes in patients with acromegaly. The histologic, immunohistochemical and electron microscopic study provided conclusive evidence that a marked diversity exists between the tumors which secrete growth hormone (GH) in excess, such as...

  • GH-Inhibitory Activity of Novel Somatostatin Agonists: Potential Applications in Acromegaly. Dasgupta, P. // Current Medicinal Chemistry - Immunology, Endocrine & Metabolic ;Jun2005, Vol. 5 Issue 3, p277 

    Acromegaly is a relatively rare debilitating disease caused by hypersecretion of growth hormone (GH). Despite a multimodality approach involving surgery, radiation, dopamine agonists and somatostatin agonists the management of acromegaly in some patients has remained a challenge. Although,...

  • somatostatin analogues. Peters, Michael // BMA A-Z Family Medical Encyclopedia;2004, p702 

    An encyclopedia entry for "somatostatin analogues" is presented. It is a medical term which refers to the synthetic version of somatostatin, a growth hormone inhibiting hormone. Somatostatin analogues is designed to treat acromegaly and symptoms associated with carcinoid syndrome. One example of...

  • IS STILL PLACE FOR NEW SOMATOSTATIN ANALOGS IN THE TREATMENT OF PITUITARY ADENOMAS ? Saveanu, A. // Acta Endocrinologica (1841-0987);Jul-Sep2007, Vol. 3 Issue 3, p323 

    Multi-sst ligand drugs, as pasireotide, and dopamine-somatostatin chimeras are presented as new opportunities in the treatment of pituitary adenomas. Nevertheless, actual somatostatin receptor (sst) analogs, octreotide and lanreotide, associated to surgery, radiotherapy and GH receptors...

  • Ectopic acromegaly due to a GH-secreting pituitary adenoma in the sphenoid sinus: a case report and review of the literature. Ramírez, Claudia; Hernández-Ramirez, Laura-Cristina; Espinosa-de-los-Monteros, Ana-Laura; Franco, Juan Manuel; Guinto, Gerardo; Mercado, Moises // BMC Research Notes;2013, Vol. 6 Issue 1, p1 

    Background In more than 98% of cases, acromegaly is due to a GH-secreting pituitary adenoma. The term "ectopic acromegaly" includes neuroendocrine tumors secreting GH releasing hormone (GHRH), usually located in the lungs, thymus and endocrine pancreas. Considerably less frequent are cases of...

  • THE AFFINITY OF RECEPTOR SPECIFIC PEPTIDES 111IN-DOTA-NOC AND 111IN-DOTA-TATE TO SOMATOSTATIN RECEPTORS IN VIVO AND IN VITRO. Melicharova, Ludmila; Laznicek, Milan; Laznickova, Alice; Petrik, Milos // Biomedical Papers of the Medical Faculty of Palacky University i;2007, Vol. 151, p55 

    An abstract of the medical research "THE AFFINITY OF RECEPTOR SPECIFIC PEPTIDES 111IN-DOTA-NOC AND 111IN-DOTA-TATE TO SOMATOSTATIN RECEPTORS IN VIVO AND IN VITRO," by Ludmila Melicharova, Milan Laznicek, Alice Laznickova and Milos Petrik is presented.

Share

Read the Article

Courtesy of THE LIBRARY OF VIRGINIA

Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics