New chemotherapy agents for small cell lung cancer

Approximately 45,000 new cases of small cell lung cancer (SCLC) will be diagnosed in the United States this year. Combination chemotherapy is the cornerstone of treatment for all stages of this disease and results in high response rates (65 to 85%), leading to a meaningful survival advantage for these patients. Patients with limited-stage disease enjoy a median survival of 10 to 15 months with chemotherapy, as compared to 3 months without drug therapy. With addition of chest radiotherapy, survival is further prolonged to 12 to 20 months. Patients with extensive-stage disease experience an average survival of 1.5 months without chemotherapy and 7 to 11 months with chemotherapy. However, no further improvement in survival has been demonstrated since combination chemotherapy regimens were introduced in the late 1970s and early 1980s, despite evaluating numerous strategies; the 5-year survival for all patients remains dismal at 5%. Clearly, new chemotherapy agents with novel mechanisms of action are needed.

This article will review the experience to date with six new agents that are active against SCLC. It includes two taxanes (paclitaxel and docetaxel), vinorelbine, two camptothecin derivatives (topotecan and irinotecan), and gemcitabine. Single-agent activity as well as combination regimens with other agents and radiotherapy will be discussed. The role of maintenance therapy with oral matrix metalloproteinase inhibitors also is evaluated.