Future directions in the treatment of non-small cell lung cancer

In recent years significant advances have been made in the treatment of metastatic non-small cell lung cancer. These advances have been due to both the discovery of new, more active drugs and an enhanced understanding of the biology of the disease, which has guided treatment decisions. Today, agents such as paclitaxel, docetaxel, vinorelbine, irinotecan, and gemcitabine are used in combinations that have demonstrated higher overall response rates and longer median overall survival durations than the previous generation of regimens based primarily on cisplatin, etoposide, and vinblastine. Of these new agents, paclitaxel has been the most widely studied and has demonstrated considerable activity when administered in a wide range of doses and schedules. Regimens with significant activity include paclitaxel and carboplatin as well as paclitaxel, carboplatin, and gemcitabine. However, because the optimal doses and schedules have not been clearly elucidated, current research efforts continue to focus on variations of these regimens. Just as advances have been made in the treatment of metastatic disease, it also has been clearly demonstrated that preoperative chemotherapy (+/- radiation) dramatically improves the overall survival for patients with stage III disease. The identification of growth factors, growth factor receptors, oncogenes, and tumor suppressor genes, which influence this disease, is providing new targets for future treatment strategies. Likewise, new therapeutic entities such as antiangiogenesis agents and matrix metalloproteinase inhibitors are being evaluated.