E R Brown1, K A Charles2, 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, J F Smyth6. 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. 6. University of Edinburgh, Cancer Research Centre, Crewe Road South, Cancer Research UK Building, Edinburgh EH4 2XR, UK. Electronic address: john.smyth@ed.ac.uk.
Abstract
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.
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.
Authors: Justin M M Cates; David B Friedman; Erin H Seeley; William D Dupont; Herbert S Schwartz; Ginger E Holt; Richard M Caprioli; Pampee P Young Journal: Int J Exp Pathol Date: 2010-03-26 Impact factor: 1.925