Therapeutic advances in second-line treatment of advanced non-small-cell lung cancer

A majority of patients with lung cancer present with advanced disease: approximately 30% with locally advanced disease and 45% with metastatic disease. The prognosis for these patients is poor, with 5-year survival rates ranging from 5% to 15% for stage IIIB disease and < 5% for stage IV disease. For patients confronting advanced disease, chemotherapy is an essential option for disease control and palliation. Although a number of effective first-line regimens exist, virtually all patients with advanced non-small-cell lung cancer (NSCLC) will have disease relapse. For these patients, identifying the optimal treatment course remains a challenge. This article reviews approved and investigational second-line therapeutic options in patients with relapsed advanced NSCLC. Recently, docetaxel has been shown to improve survival in patients with advanced NSCLC who had progressive disease following treatment with platinum-containing chemotherapy. Subsequently, permetrexed was compared with docetaxel in a second-line treatment study that showed survival for both patient groups was virtually identical. Recently, erlotinib was associated with significantly longer survival compared with best supportive care in the second- or third-line treatment settings. Salvage treatment for NSCLC is reviewed, and the relative merits of the currently available treatments as well as agents that are pending Food and Drug Administration approval as second-line treatments are discussed.