Cetuximab in combination therapy from bench to cl

Authors: David E Gerber Hak Choy

Publish Date: 2010/02/08

Volume: 29, Issue: 1, Pages: 171-180

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Abstract

Cetuximab a chimeric IgG1 monoclonal antibody directed against the ligandbinding domain of the epidermal growth factor receptor offers a paradigm for the combination of molecularly targeted therapies with cytotoxic agents In preclinical models the addition of cetuximab to chemotherapy or radiation therapy enhances antitumor activity Proposed mechanisms include reducing tumor cell proliferation angiogenesis and DNA repair capacity increasing apoptosis and inducing cell cycle arrest at treatmentsensitive points These effects may enhance and restore tumor sensitivity to cytotoxic therapies In clinical trials the addition of cetuximab to chemotherapy improves outcomes of patients who had previously failed such agents as illustrated in irinotecanresistant and oxaliplatinrefractory metastatic colorectal cancer As initial therapy the addition of cetuximab to chemotherapy extends survival in colorectal cancer lung cancer and head and neck cancer Combining cetuximab with radiation therapy extends survival in locally advanced head and neck cancer As predictive biomarkers are identified it may become possible to select patients most likely to benefit from such combinations

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