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

E. R. Brown; K. A. Charles; S. A. Hoare; R. L. Rye; D. I. Jodrell; R. E. Aird; R. Vora; U. Prabhakar; M. Nakada; R. E. Corringham; M. DeWitte; C. Sturgeon; D. Propper; F. R. Balkwill; J. F. Smyth

doi:10.1093/annonc/mdn054

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

E. R. Brown, K. A. Charles, S. A. Hoare, R. L. Rye, D. I. Jodrell, R. E. Aird, R. Vora, U. Prabhakar, M. Nakada, R. E. Corringham, M. DeWitte, C. Sturgeon, D. Propper, F. R. Balkwill, J. F. Smyth

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Abstract / Description of output

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.

Original language	English
Pages (from-to)	1340-1346
Number of pages	7
Journal	Annals of Oncology
Volume	19
Issue number	7
DOIs	https://doi.org/10.1093/annonc/mdn054
Publication status	Published - Jul 2008

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Brown, E. R., Charles, K. A., Hoare, S. A., Rye, R. L., Jodrell, D. I., Aird, R. E., Vora, R., Prabhakar, U., Nakada, M., Corringham, R. E., DeWitte, M., Sturgeon, C., Propper, D., Balkwill, F. R., & Smyth, J. F. (2008). A clinical study assessing the tolerability and biological effects of infliximab, a TNF-alpha inhibitor, in patients with advanced cancer. Annals of Oncology, 19(7), 1340-1346. https://doi.org/10.1093/annonc/mdn054

@article{67d437c8fac84cbe876d983c1975b7c7,

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.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.",

author = "Brown, {E. R.} and Charles, {K. A.} and Hoare, {S. A.} and Rye, {R. L.} and Jodrell, {D. I.} and Aird, {R. E.} and R. Vora and U. Prabhakar and M. Nakada and Corringham, {R. E.} and M. DeWitte and C. Sturgeon and D. Propper and Balkwill, {F. R.} and Smyth, {J. F.}",

year = "2008",

month = jul,

doi = "10.1093/annonc/mdn054",

language = "English",

volume = "19",

pages = "1340--1346",

journal = "Annals of Oncology",

issn = "0923-7534",

publisher = "Elsevier",

number = "7",

}

Brown, ER, Charles, KA, Hoare, SA, Rye, RL, Jodrell, DI, Aird, RE, Vora, R, Prabhakar, U, Nakada, M, Corringham, RE, DeWitte, M, Sturgeon, C, Propper, D, Balkwill, FR & Smyth, JF 2008, 'A clinical study assessing the tolerability and biological effects of infliximab, a TNF-alpha inhibitor, in patients with advanced cancer', Annals of Oncology, vol. 19, no. 7, pp. 1340-1346. https://doi.org/10.1093/annonc/mdn054

TY - JOUR

T1 - A clinical study assessing the tolerability and biological effects of infliximab, a TNF-alpha inhibitor, in patients with advanced cancer

AU - Brown, E. R.

AU - Charles, K. A.

AU - Hoare, S. A.

AU - Rye, R. L.

AU - Jodrell, D. I.

AU - Aird, R. E.

AU - Vora, R.

AU - Prabhakar, U.

AU - Nakada, M.

AU - Corringham, R. E.

AU - DeWitte, M.

AU - Sturgeon, C.

AU - Propper, D.

AU - Balkwill, F. R.

AU - Smyth, J. F.

PY - 2008/7

Y1 - 2008/7

N2 - 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.

AB - 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.

U2 - 10.1093/annonc/mdn054

DO - 10.1093/annonc/mdn054

M3 - Article

SN - 0923-7534

VL - 19

SP - 1340

EP - 1346

JO - Annals of Oncology

JF - Annals of Oncology

IS - 7

ER -

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

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