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

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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. © 2012 Cancer Research UK. All rights reserved.

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Prado, C. M. M., Bekaii-Saab, T., Doyle, L. A., Shrestha, S., Ghosh, S., Baracos, V. E., & Sawyer, M. B. (2012). Skeletal muscle anabolism is a side effect of therapy with the MEK inhibitor: Selumetinib in patients with cholangiocarcinoma. British Journal of Cancer, 106(10), 1583–1586. https://doi.org/10.1038/bjc.2012.144

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