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

• Author(s) / Creator(s)

  • Ghosh, Sunita
  • Doyle, L. Austin
  • Baracos, Vickie E.
  • Prado, Carla M.
  • Sawyer, Michael B.
  • Bekaii-Saab, Tanios
  • Shrestha, Suraj

• 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 cm2/100 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 cm2/100 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.

• Date created

  2012

• Subjects / Keywords

  • Cholangiocarcinoma
  • Skeletal muscles
  • Cachexia
  • Interleukin-6

• Type of Item

  Article (Published)

• DOI

  https://doi.org/10.7939/R36970B5C

• License

  © 2012 Cancer Research UK, distributed under an Attribution-NonCommerical-ShareALike 4.0 International