BACKGROUND: Approximately 150,000 people were diagnosed with non-small cell lung cancer (NSCLC) in the United States in 2005. Most presented with inoperable advanced-stage disease. Although combination chemotherapy remains the standard treatment, median survival with these regimens is only 8 to 10 months. Recent advances in our understanding of lung cancer on a molecular level have led to the introduction of targeted therapies. METHODS: We reviewed the mechanism of action of gefitinib and erlotinib as well as the results of phase I, II, and III trials with these drugs. RESULTS: No survival advantage was seen with the addition of gefitinib or erlotinib to combination chemotherapy in first-line treatment of advanced NSCLC. Erlotinib has shown a survival advantage over placebo in patients with NSCLC after first- or second-line chemotherapy. Recently, mutations in the epidermal growth factor receptor-tyrosine kinase domain have been identified. Patients who express these mutations have shown a higher probability of response to gefitinib. CONCLUSIONS: Combination chemotherapy remains the first-line treatment of advanced NSCLC. The benefit of alternating drug schedules and combinations has been small. Targeted therapies such as gefitinib and erlotinib, although to date have shown no survival advantage when combined with chemotherapy in the first-line setting, remain promising. Ongoing studies of patient characteristics of responding patients and molecular studies of tumors may help to identify patients most likely to respond to these therapies.
BACKGROUND: Approximately 150,000 people were diagnosed with non-small cell lung cancer (NSCLC) in the United States in 2005. Most presented with inoperable advanced-stage disease. Although combination chemotherapy remains the standard treatment, median survival with these regimens is only 8 to 10 months. Recent advances in our understanding of lung cancer on a molecular level have led to the introduction of targeted therapies. METHODS: We reviewed the mechanism of action of gefitinib and erlotinib as well as the results of phase I, II, and III trials with these drugs. RESULTS: No survival advantage was seen with the addition of gefitinib or erlotinib to combination chemotherapy in first-line treatment of advanced NSCLC. Erlotinib has shown a survival advantage over placebo in patients with NSCLC after first- or second-line chemotherapy. Recently, mutations in the epidermal growth factor receptor-tyrosine kinase domain have been identified. Patients who express these mutations have shown a higher probability of response to gefitinib. CONCLUSIONS: Combination chemotherapy remains the first-line treatment of advanced NSCLC. The benefit of alternating drug schedules and combinations has been small. Targeted therapies such as gefitinib and erlotinib, although to date have shown no survival advantage when combined with chemotherapy in the first-line setting, remain promising. Ongoing studies of patient characteristics of responding patients and molecular studies of tumors may help to identify patients most likely to respond to these therapies.