Rationale and clinical validation of epidermal growth factor receptor as a target in the treatment of head and neck cancer.
Recurrent/metastatic head and neck cancer is an area of high, unmet treatment need. There is a strong rationale for targeting the epidermal growth factor receptor (EGFR) in head and neck cancer as most of these tumors express high levels of EGFR relative to normal tissue, with high expression correlating with poor patient outcome. This rationale has been validated in extensive preclinical studies. Two small molecules with EGFR inhibitory activity, gefitinib ('Iressa', ZD1839) and erlotinib ('Tarceva', OSI-774), and a humanized monoclonal antibody against the EGFR extracellular domain, cetuximab ('Erbitux', C225), are in clinical trials for advanced head and neck cancer. The initial results of these trials are promising. Gefitinib and erlotinib show activity as monotherapy in patients with recurrent or metastatic head and neck cancer, and have an acceptable safety profile compared with conventional chemotherapy. Gefitinib, which can be given at doses below the maximum tolerated dose, is associated with slightly lower rates of adverse events than erlotinib, which is dosed at the maximum tolerated dose. Combinations of cetuximab with radiotherapy or platinum-based chemotherapy have also shown activity in phase I/II studies. Both gefitinib and cetuximab have entered phase III studies. The results of these trials, which will mature over the next few years, will help determine the optimal use of EGFR agents in head and neck cancers.
Caponigro
Francesco
F
Istituto Nazionale per lo Studio e la Cura dei Tumori 'Fondazione G. Pascale', Naples, Italy. caponigrof@libero.it
D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D000068818:Cetuximab; D002986:Clinical Trials as Topic; D016503:Drug Delivery Systems / Q000379:methods*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D000069347:Erlotinib Hydrochloride; D000077156:Gefitinib; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000209:etiology; D006801:Humans; D011799:Quinazolines / Q000008:administration & dosage / Q000627:therapeutic use
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D011799:Quinazolines; D000069347:Erlotinib Hydrochloride; D066246:ErbB Receptors; D000068818:Cetuximab; D000077156:Gefitinib