Combined-modality treatment of locally advanced non-small cell lung cancer: incorporation of novel chemotherapeutic agents.

The role of multimodality management in locally advanced non-small cell lung cancer (NSCLC) continues to evolve and is a subject of ongoing clinical research. Induction chemotherapy followed by surgical resection with or without thoracic radiotherapy has proved superior to surgical resection alone in patients with ipsilateral mediastinal (N2) disease. Whether surgery alone still plays a role in these patients is the subject of an ongoing intergroup study. As no definitive, optimal effective chemotherapy regimen currently exists for NSCLC, future studies will attempt to incorporate novel and active agents like the taxanes, irinotecan, vinorelbine, and gemcitabine into combined-modality therapy for locally advanced NSCLC. Thoracic radiation therapy by itself provides local control and effective palliation of tumor-related symptoms but has minimal impact on the survival of patients with locally advanced disease. Novel schemes such as hyperfractionated radiotherapy and continuous hyperfractionated accelerated radiotherapy are currently being investigated and appear promising but need to be tested in combination with chemotherapeutic agents. Randomized studies have demonstrated the benefit of concurrent or sequential chemoradiation in selected patients with a good performance status and minimal weight loss. The exact sequence of combined-modality therapy has yet to be determined. The combination of paclitaxel and platinum compounds has shown impressive activity in advanced NSCLC in both phase II and III randomized studies. We have incorporated weekly low-dose paclitaxel and carboplatin with concurrent thoracic radiation in treating patients with locally advanced, inoperable NSCLC, and long-term follow-up has shown remarkable survival rates. Confirmation of these phase II combined-modality studies is needed. Combination sequential chemotherapy followed by concurrent chemoradiation in patients with advanced NSCLC has the potential to improve overall survival by increasing both local and distant control.