Author | Hak Choy, MD


Chemoradiation in NSCLC: Focus on the Role of Gemcitabine

July 01, 2004

Research to identify the optimal drugs for use in chemoradiotherapyhas led to the development of the potent radiosensitizing agentgemcitabine (Gemzar), which has exhibited excellent activity in non-small-cell cancer. When used in sequential chemoradiotherapy regimens,gemcitabine has been associated with response rates of 57% to68%. A full dose of gemcitabine (1,000 mg/m2) can be safely used asinduction therapy, and there is no definitive indication of enhancementof radiotoxicity. In addition, results from phase I/II trials supportthe efficacy of concurrent gemcitabine/radiation therapy in improvingoverall response rates and overall survival. Rates of 68%, 37%, and28%, respectively, for 1-, 2-, and 3-year survival have been reported forgemcitabine/cisplatin chemotherapy administered concurrently withradiotherapy. Although the optimal dose has yet to be determined, aweekly dose of 300 mg/m2 appears to be effective with an acceptabletoxicity level. Additional clinical trials are warranted to assess the longtermefficacy and safety of gemcitabine in combination with other chemotherapeuticagents and radiation therapy for treatment of non-smallcelllung cancer.

Topoisomerase I Inhibitors in the Combined-Modality Therapy of Lung Cancer

June 01, 2004

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.

Irinotecan in Combination With Radiation Therapy for Small-Cell and Non-Small-Cell Lung Cancer

September 02, 2002

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.

Irinotecan and Radiation in Combined-Modality Therapy for Solid Tumors

July 01, 2001

Irinotecan (CPT-11, Camptosar) is a camptothecin derivative thatis thought to exert its cytotoxic effects by targeting topoisomerase