Skeletal muscle anabolism is a side effect of therapy with the MEK inhibitor: selumetinib in patients with cholangiocarcinoma

Br J Cancer. 2012 May 8;106(10):1583-6. doi: 10.1038/bjc.2012.144. Epub 2012 Apr 17.


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.

Conclusion: Our findings suggest that selumetinib promotes muscle gain in patients with cholangiocarcinoma. Specific mechanisms and relevance for cachexia therapy remain to be investigated.

Publication types

  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Benzimidazoles / adverse effects*
  • Bile Duct Neoplasms / drug therapy*
  • Bile Duct Neoplasms / mortality
  • Bile Ducts, Intrahepatic*
  • Cachexia / drug therapy
  • Cholangiocarcinoma / drug therapy*
  • Cholangiocarcinoma / mortality
  • Female
  • Humans
  • Male
  • Middle Aged
  • Mitogen-Activated Protein Kinase Kinases / antagonists & inhibitors*
  • Muscle, Skeletal / drug effects*
  • Muscle, Skeletal / metabolism
  • Protein Kinase Inhibitors / adverse effects*


  • AZD 6244
  • Benzimidazoles
  • Protein Kinase Inhibitors
  • Mitogen-Activated Protein Kinase Kinases