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

C. M.M. Prado, T. Bekaii-Saab, L. A. Doyle, S. Shrestha, S. Ghosh, V. E. Baracos, M. B. Sawyer

Research output: Contribution to journalArticlepeer-review

76 Scopus citations

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

Original languageEnglish (US)
Pages (from-to)1583-1586
Number of pages4
JournalBritish journal of cancer
Volume106
Issue number10
DOIs
StatePublished - May 8 2012

Keywords

  • Cachexia
  • Cholangiocarcinoma
  • Interleukin-6
  • Skeletal muscle

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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