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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miscellaneous tumors |
A clinical study assessing the tolerability and biological effects of infliximab, a TNF-
inhibitor, in patients with advanced cancer
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-
(TNF-) is an important regulator of the chronic inflammation contributing to tumour progression. Infliximab, an anti-TNF- 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-, 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- 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- and CCL2 being correlated with infliximab response.
Key words:
cytokine, inflammation, infliximab, TNF-, trial
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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