Non-small-cell lung cancer progression after first-line chemotherapy

Platinum-based chemotherapy is the cornerstone of care for patients with metastatic non-small-cell lung cancer (NSCLC). It provides symptom relief, improved quality of life, and prolongation of life, compared with supportive care alone. However, all patients with stage IV disease inevitably develop resistance to chemotherapy and progressive disease. Many of these patients continue to have acceptable performance status and would therefore be eligible for second-line or even third-line treatments. Unfortunately, despite an increasing number of chemotherapeutic agents (which are effective in chemo-naive NSCLC), very few have been shown to have reproducible activity in the second-line setting. Nevertheless, recent randomized clinical trials have demonstrated that single-agent docetaxel improves survival and quality of life when delivered as second-line therapy, resulting in FDA-approval for this indication. Phase II studies evaluating other new agents, delivered singly or in combination, also have reported that gemcitabine, weekly paclitaxel, and the epidermal growth factor receptor (EGFR) inhibitors are active in a subset of patients who progress after first-line platinum-based therapy. Clinical trials are imperative in identifying additional new agents and approaches that may improve outcomes in this disease. In view of the recently established role of docetaxel, ongoing randomized studies are using a common design of single-agent docetaxel versus docetaxel plus a novel investigational agent.