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

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

Research output: Contribution to journalArticle

62 Citations (Scopus)

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
Externally publishedYes

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Cholangiocarcinoma
Mitogen-Activated Protein Kinase Kinases
Skeletal Muscle
Muscles
Cachexia
Therapeutics
Mitogen-Activated Protein Kinase 12
AZD 6244
Group Psychotherapy
Mitogens
Interleukin-6
Neoplasms
Tomography

Keywords

  • Cachexia
  • Cholangiocarcinoma
  • Interleukin-6
  • Skeletal muscle

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Skeletal muscle anabolism is a side effect of therapy with the MEK inhibitor : Selumetinib in patients with cholangiocarcinoma. / Prado, C. M.M.; Bekaii-Saab, Tanios; Doyle, L. A.; Shrestha, S.; Ghosh, S.; Baracos, V. E.; Sawyer, M. B.

In: British Journal of Cancer, Vol. 106, No. 10, 08.05.2012, p. 1583-1586.

Research output: Contribution to journalArticle

Prado, C. M.M. ; Bekaii-Saab, Tanios ; Doyle, L. A. ; Shrestha, S. ; Ghosh, S. ; Baracos, V. E. ; Sawyer, M. B. / Skeletal muscle anabolism is a side effect of therapy with the MEK inhibitor : Selumetinib in patients with cholangiocarcinoma. In: British Journal of Cancer. 2012 ; Vol. 106, No. 10. pp. 1583-1586.
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