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Annals of Oncology Advance Access originally published online on March 5, 2008
Annals of Oncology 2008 19(7):1340-1346; doi:10.1093/annonc/mdn054
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© The Author 2008. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org

miscellaneous tumors

A clinical study assessing the tolerability and biological effects of infliximab, a TNF-{alpha} inhibitor, in patients with advanced cancer

E. R. Brown1,{dagger}, K. A. Charles2,{dagger}, S. A. Hoare2, R. L. Rye1, D. I. Jodrell1, R. E. Aird1, R. Vora3, U. Prabhakar3, M. Nakada3, R. E. Corringham3, M. DeWitte3, C. Sturgeon4, D. Propper5, F. R. Balkwill2 and J. F. Smyth1,*

1 University of Edinburgh, Cancer Research Centre, Crewe Road South, Cancer Research UK Building, Edinburgh EH4 2XR, UK
2 Centre for Translational Oncology, Institute of Cancer and the CR-UK Clinical Centre, Barts and The London, Queen Mary's School of Medicine and Dentistry, Charterhouse Square, London, EC1M 6BQ, UK
3 Centocor R&D Inc., Malvern, PA 19355, USA
4 Department of Clinical Biochemistry, Edinburgh Royal Infirmary, Edinburgh EH16 4SA, UK
5 Cancer Research UK, Medical Oncology Unit, St Bartholomew's Hospital, West Smithfield, London EC1A 7BE, UK

* Correspondence to: Prof. J. F. Smyth, University of Edinburgh, Cancer Research Centre, Crewe Road South, Cancer Research UK Building, Edinburgh EH4 2XR, UK. Tel: +44-131777-3512; Fax: +44-131-777-3520; E-mail: john.smyth{at}ed.ac.uk

Background: Tumour necrosis factor-{alpha} (TNF-{alpha}) is an important regulator of the chronic inflammation contributing to tumour progression. Infliximab, an anti-TNF-{alpha} monoclonal antibody was investigated in this trial of patients with advanced cancer. The primary objectives were to determine the safety profile and biological response of infliximab in a cancer population. Clinical response was a secondary objective.

Patients and methods: Forty-one patients received infliximab at 5 mg/kg (n = 21) or 10 mg/kg (n = 20) i.v. at 0 and 2 weeks and then every 4 weeks. Post-treatment samples were measured for changes in plasma and serum TNF-{alpha}, CCL2, IL-6 and C-reactive protein (CRP).

Results: Infliximab was well tolerated with no dose-limiting toxic effects. At both doses of infliximab, neutralisation of serum TNF-{alpha} was observed after 1 h while plasma CCL2, IL-6 and serum CRP were decreased 24 and 48 h following infliximab administration. Seven patients experienced disease stablisation (range 10–50+ weeks). There was no evidence of disease acceleration in any patient.

Conclusions: Infliximab treatment was safe and well tolerated in patients with advanced cancer. There was evidence of biological activity with baseline TNF-{alpha} and CCL2 being correlated with infliximab response.

Key words: cytokine, inflammation, infliximab, TNF-{alpha}, trial

{dagger} These authors contributed equally to this work.

Received for publication December 6, 2007. Revision received February 1, 2008. Accepted for publication February 5, 2008.


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