title: Pasireotide in Acromegaly: An Overview of Current Mechanistic and Clinical Data.
abstract: BACKGROUND
  Acromegaly is an insidious neuroendocrine disorder caused by hypersecretion of growth hormone (GH) by a somatotroph adenoma. Somatostatin receptor ligands (SRLs) are recommended as first-line medical therapy in patients for whom surgery has failed or is contraindicated. There are 5 known somatostatin receptor subtypes (SSTRs), 2 of which, i.e. SSTR2 and SSTR5, are expressed by a majority of somatotroph adenomas. The currently available SRLs, i.e. octreotide and lanreotide, primarily bind to SSTR2. Pasireotide (SOM230) is a new multireceptor-targeted SRL which has a broader binding profile and an increased affinity for SSTR1, 2, 3, and 5.
  
  
  METHODS
  PubMed searches were performed to identify all of the available published English language data on pasireotide with regard to the mechanism of action, in vitro effects, and clinical data.
  
  
  RESULTS
  Preclinical studies have demonstrated that pasireotide has a broader range of functional activity than octreotide. Recently, the efficacy of pasireotide in attenuating GH and insulin-like growth factor 1 (IGF-1) levels in patients with acromegaly has been evaluated in phase III clinical trials. Pasireotide demonstrated superiority over octreotide in achieving biochemical control (i.e. GH ≤2.5 µg/l and age- and sex-matched IGF-1 normalization) in patients with acromegaly, as well as significant efficacy in treating patients who were previously inadequately controlled on the maximum allowed doses of octreotide and lanreotide. Pasireotide-induced hyperglycemia was the most concerning adverse event but was reversible upon discontinuation of pasireotide.
  
  
  CONCLUSIONS
  The clinical data support pasireotide as a promising new therapy for the treatment of acromegaly, and the long-acting formulation was recently approved in the US and Europe for the treatment of acromegaly.
authors: The Pituitary Center at Baylor St. Luke's Medical Center, Division of Endocrinology, Department of Medicine, Baylor College of Medicine, Houston, Tex., USA.
authors: Susan L
authors: SL
authors: Samson
mesh_terms: D000172:Acromegaly / Q000188:drug therapy* / Q000378:metabolism; D000818:Animals; D002986:Clinical Trials as Topic; D013006:Growth Hormone / Q000378:metabolism; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008297:Male; D015282:Octreotide / Q000493:pharmacokinetics / Q000627:therapeutic use; D010456:Peptides, Cyclic / Q000493:pharmacokinetics / Q000627:therapeutic use; D017481:Receptors, Somatostatin / Q000819:agonists; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D010456:Peptides, Cyclic; D017481:Receptors, Somatostatin; C060347:lanreotide; D013004:Somatostatin; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; C517782:pasireotide; D015282:Octreotide