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

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 (similar to 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 (similar to 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. British Journal of Cancer (2012) 106, 1583-1586. doi:10.1038/bjc.2012.144 www.bjcancer.com Published online 17 April 2012 (C) 2012 Cancer Research UK