Treatment of advanced (stages III and IV) non-small-cell lung cancer

Lung cancer is the leading cause of cancer deaths, and approximately 85% of patients in whom this neoplasm is diagnosed will die of this disease as a result of micrometastatic disease from tumors that appeared surgically resectable or of surgically unresectable disease that is either locally advanced or metastatic. It will affect approximately 171,000 people in the United States in 1998 and about 75% of these cases will be non-small-cell lung cancer (NSCLC). In only 25% of cases can complete surgical resection and cure be considered. Despite this grim outlook, advances have recently been made that beckon in an era of cautious optimism. In this review, a discussion of the latest developments in the management of locally advanced and metastatic NSCLC will be presented in detail. One of the significant developments has been the modifications to the staging system after the natural history of various stages was better characterized by reviewing the outcome of more than 5000 patients. Advances have also been seen in the diagnostic field. Specifically, positron emission tomography and endoscopic ultrasonography and biopsy are being evaluated to determine their role in diagnosing and staging lung cancer. At the present, however, history and physical examination, serum evaluation, computed tomography, and conventional approaches for obtaining a histologic diagnosis are standard practice. The role of adjuvant therapy, both postoperatively and in the neoadjuvant setting, has been studied. There are no data to support the use of radiotherapy or chemotherapy, with or without radiotherapy, in the postoperative setting. In the neoadjuvant setting, some intriguing results in favor of adjuvant chemotherapy have been observed. As discussed in detail these results provide preliminary data and need to be evaluated on a larger scale. Before the 1990s radiotherapy was the principal treatment modality used in the treatment of patients with locally advanced NSCLC. However, the results of several studies have shown the superiority of chemotherapy and radiotherapy in combination for patients with unresectable stage III NSCLC. Many questions regarding the optimal modes of chemotherapy and radiotherapy and the timing of these two modalities have yet to be answered. Concurrent with these advances has been the development of new chemotherapeutic agents that have been extensively evaluated in phase I and II trials. These agents include gemcitabine, paclitaxel, docetaxel, vinorelbine, and irinotecan. These agents have shown significant activity and acceptable toxicity when used in combination with cisplatin or carboplatin, but the results from the large cooperative trials that are ongoing are eagerly awaited to help define the optimal regimen. Further studies are either planned or ongoing to further define the role of these newer agents in the treatment of metastatic disease, in combination with radiotherapy for unresectable disease, and in the surgical adjuvant setting.