Lung cancer is the most lethal cancer in both men and women, accounting for 28% of all cancer deaths, and in absolute numbers representing more than 150,000 deaths annually in the United States.<sup>17 Boring C.C., Squires T.S., Tong T. , e al. Cancer statistics, 1994 CA Cancer J Clin 1994 ;  44 : 7  [cross-ref]

Cliccare qui per andare alla sezione Riferimenti</sup> This number is more than the combined deaths from breast, colon, and prostate cancer. The overall 5-year survival rate for patients developing lung cancer is approximately only 13%. Most of the deaths are secondary to metastatic spread of the disease.

Lung cancer is staged according to a four-stage system described by Mountain<sup>126 Mountain C.F. A new international staging system for lung cancer Chest 1986 ;  89 (suppl) : 225S-233S

Cliccare qui per andare alla sezione Riferimenti, 127 Mountain C.F. The new international staging system for lung cancer Surg Clin North Am 1987 ;  67 : 925

Cliccare qui per andare alla sezione Riferimenti</sup> in 1986. By that classification, the majority of lung cancer patients present with inoperable stage III disease or with metastases to distant organs (stage IV).<sup>126 Mountain C.F. A new international staging system for lung cancer Chest 1986 ;  89 (suppl) : 225S-233S

Cliccare qui per andare alla sezione Riferimenti, 127 Mountain C.F. The new international staging system for lung cancer Surg Clin North Am 1987 ;  67 : 925

Cliccare qui per andare alla sezione Riferimenti</sup> Patients with stage IIIB or IV disease cannot be cured with current chemotherapeutic approaches, and hence all measures are aimed at prolongation of life and palliation of symptoms as well as improving quality of life.

Given that chemotherapy for advanced disease is marginally beneficial and noncurative, its use must be governed judiciously, with each decision being evaluated individually for each patient. In addition, given this fact, intensive efforts have been devoted to the development of chemotherapeutic regimens that can improve survival as well as quality of life. The latter is, of course, a subjective endpoint, and extensive efforts are underway worldwide to develop tools for its measurement. Current chemotherapeutic approaches consist initially of defining new combinations of established chemotherapeutic agents that may act synergistically. In addition, new drugs with novel mechanisms of action are also being investigated, both as single agents and subsequently as agents to be used in combination with established drugs.

This report reviews major studies published over the last 20+ years in an attempt to identify systemic cytotoxic therapies that can lead to prolonged survival and/or provide palliation in patients with advanced non–small cell lung cancer (NSCLC), both as single agents and in combination regimens. Innumerable, small phase II studies have been published in NSCLC, ostensibly demonstrating improved efficacy for new single agents or new drug combinations. When subjected to the rigorous standards of well-designed, large phase III trials, however, the encouraging phase II data often did not hold up, mostly as a result of differences in patient selection factors. In contrast, relatively few well-controlled, randomized phase III studies have been carried out, although at least eight now exist that compare chemotherapy with supportive care in this disease. Their results and the subsequent meta-analyses will be reviewed. Finally, we will explore the newer drugs and combinations now actively under study for the treatment of this challenging malignant disease.