Combined therapies for cancer: a review of EGFR-targeted monotherapy and combination treatment with other drugs
The epidermal growth factor receptor (EGFR) is a transmembrane tyrosine kinase (TK) receptor that is frequently expressed in many epithelial tumors. The signaling pathways of EGFR is involved in cancer cell proliferation, apoptosis, angiogenesis, invasions and metastasis. The EGFR was the first receptor to be proposed for cancer therapy and two EGFR-targeted pharmacological approaches have been successfully developed: monoclonal antibodies and small-molecule inhibitor of the EGFR TK enzymatic activity. Erlotinib is a quinazoline derivative that selectively and reversibly inhibits the TK activity of EGFR. Erlotinib, on the basis of the results of a large randomized phase III clinical trial (BR21) in which show a survival benefit versus placebo-treated patients, received regular approval for the treatment of advanced non-small-cell lung cancer (NSCLC) patients after failure a platinum-containing chemotherapy. Erlotinib was recently approved in combination with gemcitabine chemotherapy for the treatment of advanced pancreatic cancer, and continues to be investigated in a number of tumor types. Furthermore, it has been investigated the role of factors that would predict the efficacy of erlotinib treatment, including anatomoclinical, pathologic and molecular features. This review will focus on the clinical results available with erlotinib in the treatment of NSCLC, pancreatic, head and neck and other tumor types.