Novel approaches to locally advanced unresectable non-small cell lung cancer.

The management of advanced non-small cell lung cancer (NSCLC) is rapidly evolving. Advances in combined chemo-radiation therapy have led to improvements in patient survival which are statistically significant, but most patients still succumb to their disease. New chemotherapeutic agents, such as taxanes (paclitaxel, docetaxel), topoisomerase inhibitors (topotecan, irinotecan), and novel analogs (gemcitabine, vinorelbine), may offer the promise of improved outcome, but have not yet been tested in phase III trials. Molecular therapeutics, such as gene therapy, drugs that target specific oncogene activation (such as Ki-ras inactivation by farnesyl transferase inhibitors), and hypoxic cell toxins (such as tirapazamine), are in clinical trials. The optimum use of these agents awaits more rapid and widespread molecular diagnostics. Finally, technological advances in radiotherapy will allow higher tumor doses, while minimizing doses to dose-limiting normal structures, such as the esophagus, normal lung and heart. We describe a move towards molecular strategies, both for therapy and diagnostics, that may result in more effective treatment. While the outcome for patients with advanced non-small cell lung carcinoma is still poor, new agents are being developed rapidly and offer the hope of improved survival.