IMC-C225, an anti-epidermal growth factor receptor monoclonal antibody, for treatment of head and neck cancer

Squamous cell carcinoma (SCC) of the head and neck (H&N) remains a clinical challenge due to its high rate of locoregional disease recurrence. The imp ortance of the epidermal growth factor receptor (EGFR) in the development a nd progression of many solid tumours (including SCC of the H&N) is well und erstood; increased expression is associated with enhanced tumour invasion, resistance to chemotherapy and decreased patient survival. Several approach es have been developed to achieve EGFR blockade as an anticancer treatment strategy, including an anti-EGFR monoclonal antibody (mAb), IMC-C225, which competetively binds to the extracellular receptor site to prevent binding by natural EGFR ligands (EGF and TGF-alpha). Preclinical studies evaluating this chimeric mAb in human cancer cell lines in vitro and human tumour xen ografts in vivo have demonstrated its potent antitumour activity. The clini cal efficacy of IMC-C225 appears to involve multiple anticancer mechanisms, including inhibition of cell cycle progression, induction of apoptosis, an tiangiogenesis, inhibition of metastasis and its ability to enhance the res ponse to chemotherapy and radiation therapy. Phase I studies of IMC-C225 co mbined with chemotherapy or radiation for SCC of the H&N demonstrate excell ent response rates in patients with recurrent or refractory disease. Phase II and III trials examining the efficacy and safety of these combinations a re currently underway. To date, IMC-C225 has been well-tolerated, with skin rashes and allergic reactions being the most clinically important adverse events reported. IMC-C225 displays dose-dependent elimination characteristi cs and a half-life of approximately 7 days. Current recommendations for dos ing include a 400 mg/m(2) loading dose, followed by weekly infusions of 250 mg/m(2).