title: A clinical study assessing the tolerability and biological effects of infliximab, a TNF-alpha inhibitor, in patients with advanced cancer.
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.
  
  
  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.affiliation: University of Edinburgh, Cancer Research Centre, Crewe Road South, Cancer Research UK Building, Edinburgh EH4 2XR, UK.
authors.forename: E R
authors.initials: ER
authors.lastname: Brown
authors.affiliation: 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.
authors.forename: K A
authors.initials: KA
authors.lastname: Charles
authors.affiliation: 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.
authors.forename: S A
authors.initials: SA
authors.lastname: Hoare
authors.affiliation: University of Edinburgh, Cancer Research Centre, Crewe Road South, Cancer Research UK Building, Edinburgh EH4 2XR, UK.
authors.forename: R L
authors.initials: RL
authors.lastname: Rye
authors.affiliation: University of Edinburgh, Cancer Research Centre, Crewe Road South, Cancer Research UK Building, Edinburgh EH4 2XR, UK.
authors.forename: D I
authors.initials: DI
authors.lastname: Jodrell
authors.affiliation: University of Edinburgh, Cancer Research Centre, Crewe Road South, Cancer Research UK Building, Edinburgh EH4 2XR, UK.
authors.forename: R E
authors.initials: RE
authors.lastname: Aird
authors.affiliation: Centocor R&D Inc., Malvern, PA 19355, USA.
authors.forename: R
authors.initials: R
authors.lastname: Vora
authors.affiliation: Centocor R&D Inc., Malvern, PA 19355, USA.
authors.forename: U
authors.initials: U
authors.lastname: Prabhakar
authors.affiliation: Centocor R&D Inc., Malvern, PA 19355, USA.
authors.forename: M
authors.initials: M
authors.lastname: Nakada
authors.affiliation: Centocor R&D Inc., Malvern, PA 19355, USA.
authors.forename: R E
authors.initials: RE
authors.lastname: Corringham
authors.affiliation: Centocor R&D Inc., Malvern, PA 19355, USA.
authors.forename: M
authors.initials: M
authors.lastname: DeWitte
authors.affiliation: Department of Clinical Biochemistry, Edinburgh Royal Infirmary, Edinburgh EH16 4SA, UK.
authors.forename: C
authors.initials: C
authors.lastname: Sturgeon
authors.affiliation: Cancer Research UK, Medical Oncology Unit, St Bartholomew's Hospital, West Smithfield, London EC1A 7BE, UK.
authors.forename: D
authors.initials: D
authors.lastname: Propper
authors.affiliation: 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.
authors.forename: F R
authors.initials: FR
authors.lastname: Balkwill
authors.affiliation: University of Edinburgh, Cancer Research Centre, Crewe Road South, Cancer Research UK Building, Edinburgh EH4 2XR, UK. Electronic address: john.smyth@ed.ac.uk.
authors.forename: J F
authors.initials: JF
authors.lastname: Smyth
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002097:C-Reactive Protein / Q000032:analysis; D018932:Chemokine CCL2 / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004342:Drug Hypersensitivity; D005260:Female; D006801:Humans; D006968:Hypersensitivity, Delayed / Q000139:chemically induced; D000069285:Infliximab; D007262:Infusions, Intravenous; D015850:Interleukin-6 / Q000097:blood; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D012680:Sensitivity and Specificity; D013280:Stomatitis / Q000139:chemically induced; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000097:blood
chemical_list: D000911:Antibodies, Monoclonal; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein; D000069285:Infliximab