A phase 1 trial of recombinant human IL-21 in combination with cetuximab in patients with metastatic colorectal cancer

Steele, N., Anthony, A., Saunders, M., Esmarck, B., Ehrnrooth, E., Kristjansen, P.E.G., Nihlén, A., Hansen, L.T. and Cassidy, J. (2012) A phase 1 trial of recombinant human IL-21 in combination with cetuximab in patients with metastatic colorectal cancer. British Journal of Cancer, 106(5), pp. 793-798. (doi: 10.1038/bjc.2011.599)

Abstract

<p>Background: Pre-clinical data indicate enhanced anti-tumour activity when combining recombinant human interleukin-21 (rIL-21), a class 1 cytokine, with cetuximab, a monoclonal antibody, targeting the epidermal growth factor receptor. This phase 1 trial assessed the safety and tolerability of escalating doses of rIL-21 in combination with cetuximab in chemo-naïve patients with stage IV colorectal cancer.</p> <p>Patients and methods: Sequential cohorts of PS 0–1, asymptomatic patients, were treated weekly with cetuximab 250 mg m−2 intravenously (i.v.) plus escalating i.v. doses of rIL-21 following an initial loading dose of cetuximab 400 mg m−2. Initial treatment period was 8 weeks, with extension permitted in patients without disease progression.</p> <p>Results: In all, 15 patients were included in this study. Adverse events related to rIL-21 or rIL-21 plus cetuximab included lethargy, nausea/vomiting, stomatitis, lymphopenia and pyrexia and were mainly grade 2. One dose limiting toxicity occurred (grade 3 diarrhoea). Maximum tolerated dose was not determined because of the premature study closure. Maximum administered dose was 100 μg kg−1 rIL-21 weekly. In all, 60% of the patients had stable disease. Immune activation was confirmed by various T- and NK-cell activation biomarkers, including dose-dependent increases in serum sCD25.</p> <p>Conclusion: rIL-21 weekly combined with cetuximab is well tolerated at doses up to 100 μg kg−1 and results in activation of immune response biomarkers.</p>

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Steele, Dr Nicola and Cassidy, Professor James
• Authors: Steele, N., Anthony, A., Saunders, M., Esmarck, B., Ehrnrooth, E., Kristjansen, P.E.G., Nihlén, A., Hansen, L.T., and Cassidy, J.
• College/School: College of Medical Veterinary and Life Sciences > School of Cancer Sciences
• Journal Name: British Journal of Cancer
• Publisher: Nature Publishing Group
• ISSN: 0007-0920
• ISSN (Online): 1532-1827
• Published Online: 07 February 2012