Overview of current and future chemotherapeutic agents in non-small cell lung cancer

The two-drug regimen consisting of a platinum compound (cisplatin or carboplatin) combined with either a vinca alkaloid or a podophyllotoxin has been considered by many to be the standard chemotherapy treatment for non-small cell lung cancer (NSCLC). Randomized trials with these regimens have demonstrated modest but statistically significant increases in survival for patients with stage IV disease compared to treatment with best supportive care, and especially for selected patients with stage III disease when combined with radiotherapy or surgery compared to these treatments alone. Recently, several new compounds with promising efficacy and acceptable toxicity profiles have been investigated for the treatment of NSCLC, including the taxanes paclitaxel and docetaxel, the novel pyrimidine analog gemcitabine, and the topoisomerase inhibitors irinotecan and topotecan. Small but significant improvements in response rates and survival have been achieved with two-drug combinations, which include several of these new agents combined with a platinum-based compound, in patients with advanced NSCLC. Modifications of dosing schedules and the use of premedication regimens have resulted in better efficacy and more manageable side effects with such combinations. These encouraging gains in patients with advanced NSCLC suggest a potentially greater impact in patients with early stage disease. Given the manageable toxicity profiles of many of these newer agents, various three-drug regimens may be feasible in the future.