title: Skeletal muscle anabolism is a side effect of therapy with the MEK inhibitor: selumetinib in patients with cholangiocarcinoma.
abstract: BACKGROUND
  Cancer cachexia is characterised by skeletal muscle wasting; however, potential for muscle anabolism in patients with advanced cancer is unproven.
  
  
  METHODS
  Quantitative analysis of computed tomography images for loss/gain of muscle in cholangiocarcinoma patients receiving selumetinib (AZD6244; ARRY-142886) in a Phase II study, compared with a separate standard therapy group. Selumetinib is an inhibitor of mitogen-activated protein/extracellular signal-regulated kinase and of interleukin-6 secretion, a putative mediator of muscle wasting.
  
  
  RESULTS
  Overall, 84.2% of patients gained muscle after initiating selumetinib; mean overall gain of total lumbar muscle cross-sectional area was 13.6 cm(2)/100 days (∼2.3 kg on a whole-body basis). Cholangiocarcinoma patients who began standard treatment were markedly catabolic, with overall muscle loss of -7.3 cm(2)/100 days (∼1.2 kg) and by contrast only 16.7% of these patients gained muscle.
  
  
  CONCLUSIONS
  Our findings suggest that selumetinib promotes muscle gain in patients with cholangiocarcinoma. Specific mechanisms and relevance for cachexia therapy remain to be investigated.
authors.affiliation: Department of Oncology, University of Alberta, Cross Cancer Institute, 11560 University Avenue, Edmonton, Alberta T6G 1Z2, Canada.
authors.forename: C M M
authors.initials: CM
authors.lastname: Prado
authors.forename: T
authors.initials: T
authors.lastname: Bekaii-Saab
authors.forename: L A
authors.initials: LA
authors.lastname: Doyle
authors.forename: S
authors.initials: S
authors.lastname: Shrestha
authors.forename: S
authors.initials: S
authors.lastname: Ghosh
authors.forename: V E
authors.initials: VE
authors.lastname: Baracos
authors.forename: M B
authors.initials: MB
authors.lastname: Sawyer
mesh_terms: D000328:Adult; D000368:Aged; D001562:Benzimidazoles / Q000009:adverse effects*; D001650:Bile Duct Neoplasms / Q000188:drug therapy* / Q000401:mortality; D001653:Bile Ducts, Intrahepatic; D002100:Cachexia / Q000188:drug therapy; D018281:Cholangiocarcinoma / Q000188:drug therapy* / Q000401:mortality; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors*; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000009:adverse effects*
chemical_list: C517975:AZD 6244; D001562:Benzimidazoles; D047428:Protein Kinase Inhibitors; D020929:Mitogen-Activated Protein Kinase Kinases