Inhibition of epidermal growth factor receptor and symptom improvement in advanced non-small cell lung cancer

The majority of patients with non-small cell lung cancer (NSCLC) are not candidates for curative resection because of advanced disease at the time of diagnosis. Systemic chemotherapy has been employed with modest success to provide symptom relief and prolonged survival for patients with this incurable disease. Any benefit derived from chemotherapy in this palliative setting must be balanced against the substantial toxicity associated with cytotoxic drugs. A novel approach to anticancer treatment based on specific targeting molecular processes has recently demonstrated efficacy. ZD1839 is a low-molecular-weight molecule that is capable of inhibiting epidermal growth factor receptor (EGFR)-associated tyrosine kinase activity. Consequently, ZD1839 interrupts EGFR-mediated activities such as tumor cellular proliferation, motility, survival, and invasiveness. In vitro and in vivo studies have shown that ZD1839 has activity against NSCLC. The results of ZD1839 in randomized clinical trials of patients with advanced NSCLC are reported in this review. In addition to evaluating response rates and clinical endpoints, these trials prospectively evaluated symptom improvement and quality of life.