Cetuximab plus irinotecan in refractory colorectal cancer patients

Abstract

Since the mid-1980s, it has been known that the epidermal growth factor receptor, an immunoglobulin G cytoplasmic membrane protein and member of the type I subfamily of tyrosine kinase receptors, plays a key role in tumor growth and metastasis. Cetuximab is the first immunoglobulin G1 monoclonal antibody that blocks the epidermal growth factor receptor, resulting in an inhibition of tumor growth, angiogenesis, tumor spread and metastasis. Cetuximab is active in heavily pretreated colorectal cancer, as a single agent or in combination with irinotecan, a conclusion that is strongly suggested by the Bowel Oncology with Cetuximab Antibody (BOND) study in terms of response rate (11% monotherapy vs 23% in combination; p < 0.007) and time to progression (1.5 vs 4.1 months; p < 0.001). The main adverse event related to cetuximab is skin reaction, the intensity of which is correlated with efficacy. The Monoclonal Antibody Erbitux in a European Pre-License (MABEL) study has confirmed these results, recently generating a median survival of 9.2 months, comparable to 8.6 months achieved in the BOND study. Cetuximab has shown efficacy (with or without irinotecan) as second-line treatment in patients who have failed irinotecan in combination with bevacizumab, an antivascular endothelial growth factor monoclonal antibody. The combination is currently being tested in the first-line management of advanced colorectal cancer, as well as in the adjuvant setting. The evaluation of other combinations either with oxaliplatin or capecitabine, is ongoing, with preliminary reports of promising activity.

Keywords::

• advanced colorectal cancer
• cetuximab
• chemotherapy
• epidermal growth factor irinotecan
• topoisomerase I inhibitor

Acknowledgements

The authors thank Steve Johnson (Taunton and Somerset Hospital, Somerset, UK) for advice and Elodie Brever and FM Delgado for technical assistance.