Hak Choy, MD

Locally advanced non–small-cell lung cancer represents 30% to 40%of all pulmonary malignancies. Most patients will die of the diseaseafter aggressive contemporary treatments. Therefore, significant improvementin therapeutic methods must be implemented to improveoverall survival rates. The arrival of a new generation of chemotherapeuticagents-including the taxanes, gemcitabine (Gemzar), andtopoisomerase inhibitors such as irinotecan (Camptosar) and topotecan(Hycamtin)-offers the hope of significant advances in the treatmentof lung cancer. Irinotecan and topotecan are camptothecin derivativesthat inhibit topoisomerase I enzyme. It is believed that topoisomerase Iinhibitors stabilize a DNA/topoisomerase I complex and interact withreplication machinery to cause cell death. A significant amount of datademonstrates that these topoisomerase I inhibitors also act asradiosensitizers. With the increasing data that support concurrentchemoradiation treatment for malignancies, including lung cancer andhead and neck cancers, there is an impetus to pursue the additionaldrugs that may potentially improve local control and survival. Irinotecanis undergoing early clinical trials in the combined-modality setting inseveral different disease sites. This paper will review the data on therole of camptothecin derivatives as a radiosensitizer and as a componentof combined-modality therapy for lung cancer. It is hoped thatnewer treatment strategies, like the combination of radiation andtopoisomerase I inhibitors, will have a significant impact on cure ratesin the future.

Lung cancer is the leading cause of cancer-related death in the United States. There was rapid progress in the treatment of lung cancer during past decades, but local control and survival rates are still poor.

Gemcitabine has demonstrated activity in a broad range of solid tumors with good tolerance. In combined modality therapy, gemcitabine has achieved response rates ranging between 30% and 60% in patients with non-small-cell

The management of non-small-cell lung cancer is undergoing rapid evolution. Although the advent of combined-modality therapy has led to improved survival, most patients eventually succumb to the disease. The arrival of a

After nearly 4 decades of use in treating small-cell lung cancer (SCLC), thoracic radiation has become integral to the management of limited-stage disease. Many prospective randomized trials have demonstrated that adding

Preclinically, the taxanes appear to potentiate radiation more effectively than do the platinum compounds. In our phase I trial (LUN-17) in patients with advanced non-small-cell lung cancer, we defined the maximum tolerated