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

The management of advanced non-small cell lung cancer (NSCLC) is rapidly ev olving. Advances in combined chemo-radiation therapy have led to improvemen ts in patient survival which are statistically significant, but most patien ts still succumb to their disease. New chemotherapeutic agents, such as tax anes (paclitaxel, docetaxel), topoisomerase inhibitors (topotecan, irinotec an), and novel analogs (gemcitabine, vinorelbine), may offer the promise of improved outcome, but have not yet been tested in phase III trials. Molecu lar 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 hig her tumor doses, while minimizing doses to dose-limiting normal structures, such as the esophagus, normal lung and heart. We describe a move towards m olecular strategies, both for therapy and diagnostics, that may result in m ore effective treatment. While the outcome for patients with advanced non-s mall cell lung carcinoma is still poor, new agents are being developed rapi dly and offer the hope of improved survival. (C) 2000 Elsevier Science Irel and Ltd. All rights reserved.