Locally Advanced Non-Small Cell Lung Cancer: Optimal Chemotherapeutic Agents and Duration

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related mortality in the USA. The treatment of locally advanced NSCLC (LA-NSCLC) is challenging and must be individualized. For patients with completely resected stage III NSCLC, adjuvant cisplatin-based chemotherapy for 4 cycles is recommended. For patients with inoperable or unresectable stage III NSCLC, chemoradiation is the preferred treatment. Patients with a good performance status, minimal or no weight loss, and adequate pulmonary function should be offered concurrent chemoradiation. The optimal chemotherapeutic agents to be used concurrently with radiation remain undefined. In the USA, cisplatin plus etoposide or carboplatin plus paclitaxel are the most commonly used regimens. In addition, the optimal duration of therapy remains undefined, including the role of consolidation chemotherapy. Thus far, randomized phase III trials have failed to identify a survival advantage for administering chemotherapy beyond that delivered during radiation therapy. Molecularly targeted agents, angiogenesis inhibitors, and immunotherapy have a defined role for patients with metastatic disease. The role, if any, of these new classes of agents is undergoing investigation for patients with earlier stage disease, including stage III disease.