A clinical study assessing the tolerability and biological effects of infliximab, a TNF-alpha inhibitor, in patients with advanced cancer.
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.
Brown
E R
ER
University of Edinburgh, Cancer Research Centre, Crewe Road South, Cancer Research UK Building, Edinburgh EH4 2XR, UK.
Charles
K A
KA
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.
Hoare
S A
SA
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.
Rye
R L
RL
University of Edinburgh, Cancer Research Centre, Crewe Road South, Cancer Research UK Building, Edinburgh EH4 2XR, UK.
Jodrell
D I
DI
University of Edinburgh, Cancer Research Centre, Crewe Road South, Cancer Research UK Building, Edinburgh EH4 2XR, UK.
Aird
R E
RE
University of Edinburgh, Cancer Research Centre, Crewe Road South, Cancer Research UK Building, Edinburgh EH4 2XR, UK.
Vora
R
R
Centocor R&D Inc., Malvern, PA 19355, USA.
Prabhakar
U
U
Centocor R&D Inc., Malvern, PA 19355, USA.
Nakada
M
M
Centocor R&D Inc., Malvern, PA 19355, USA.
Corringham
R E
RE
Centocor R&D Inc., Malvern, PA 19355, USA.
DeWitte
M
M
Centocor R&D Inc., Malvern, PA 19355, USA.
Sturgeon
C
C
Department of Clinical Biochemistry, Edinburgh Royal Infirmary, Edinburgh EH16 4SA, UK.
Propper
D
D
Cancer Research UK, Medical Oncology Unit, St Bartholomew's Hospital, West Smithfield, London EC1A 7BE, UK.
Balkwill
F R
FR
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.
Smyth
J F
JF
University of Edinburgh, Cancer Research Centre, Crewe Road South, Cancer Research UK Building, Edinburgh EH4 2XR, UK. Electronic address: john.smyth@ed.ac.uk.
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
D000911:Antibodies, Monoclonal; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein; D000069285:Infliximab