A phase 1 trial of recombinant human IL-21 in combination with cetuximab in patients with metastatic colorectal cancer

Pre-clinical data indicate enhanced anti-tumour activity when combining recombinant human interleukin-21 (rIL-21), a class 1 cytokine, with cetuximab, a monoclonal antibody, targeting the epidermal growth factor receptor. This phase 1 trial assessed the safety and tolerability of escalating doses of...

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Bibliographic Details
Published in:British journal of cancer 2012-02, Vol.106 (5), p.793-798
Main Authors: Steele, N, Anthony, A, Saunders, M, Esmarck, B, Ehrnrooth, E, Kristjansen, P E G, Nihlén, A, Hansen, L T, Cassidy, J
Format: Article
Language:English
Subjects:
Adult
Aged
Aged, 80 and over
Antibodies, Monoclonal - administration & dosage
Antibodies, Monoclonal - adverse effects
Antibodies, Monoclonal - therapeutic use
Antibodies, Monoclonal, Humanized
Antineoplastic Agents - administration & dosage
Antineoplastic Agents - adverse effects
Antineoplastic Agents - therapeutic use
Antineoplastic Combined Chemotherapy Protocols - administration & dosage
Antineoplastic Combined Chemotherapy Protocols - adverse effects
Antineoplastic Combined Chemotherapy Protocols - therapeutic use
Asymptomatic
Biomarkers
Cancer research
Cancer therapies
Cetuximab
Chemotherapy
Clinical Study
Colorectal cancer
Colorectal Neoplasms - drug therapy
Colorectal Neoplasms - pathology
Cytokines
Epidermal growth factor
Female
Humans
Immunotherapy
Interleukins - administration & dosage
Interleukins - adverse effects
Interleukins - therapeutic use
Male
Maximum Tolerated Dose
Medical research
Metastasis
Middle Aged
Neoplasm Metastasis
Receptor, Epidermal Growth Factor - immunology
Toxicity
Treatment Outcome
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Summary:Pre-clinical data indicate enhanced anti-tumour activity when combining recombinant human interleukin-21 (rIL-21), a class 1 cytokine, with cetuximab, a monoclonal antibody, targeting the epidermal growth factor receptor. This phase 1 trial assessed the safety and tolerability of escalating doses of rIL-21 in combination with cetuximab in chemo-naïve patients with stage IV colorectal cancer. Sequential cohorts of PS 0-1, asymptomatic patients, were treated weekly with cetuximab 250 mg m(-2) intravenously (i.v.) plus escalating i.v. doses of rIL-21 following an initial loading dose of cetuximab 400 mg m(-2). Initial treatment period was 8 weeks, with extension permitted in patients without disease progression. In all, 15 patients were included in this study. Adverse events related to rIL-21 or rIL-21 plus cetuximab included lethargy, nausea/vomiting, stomatitis, lymphopenia and pyrexia and were mainly ≤ grade 2. One dose limiting toxicity occurred (grade 3 diarrhoea). Maximum tolerated dose was not determined because of the premature study closure. Maximum administered dose was 100 μg kg(-1) rIL-21 weekly. In all, 60% of the patients had stable disease. Immune activation was confirmed by various T- and NK-cell activation biomarkers, including dose-dependent increases in serum sCD25. rIL-21 weekly combined with cetuximab is well tolerated at doses up to 100 μg kg(-1) and results in activation of immune response biomarkers.
ISSN:0007-0920
1532-1827
DOI:10.1038/bjc.2011.599