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The clinical development of chemotherapeutic agents in non-small cell lung cancer (NSCLC) was initially focused in the setting of stage IV disease. During the 1980s and early 1990s, six drugs, namely cisplatin, ifosfamide, mitomycin C, etoposide, vindesine, and vinblastine, were considered active against NSCLC, with response rates reported in excess of 15%. 1,2 Combination chemotherapy, most commonly cisplatin-based, was also investigated. Generally, higher objective responses were achieved but still the benefit for the patients was unclear by that time. Subsequent randomized trials and meta-analyses established the value of chemotherapy in the treatment of patients with advanced NSCLC. 3,4 The next steps were aimed at the development of chemotherapy from a palliative measure to a curative one, through its incorporation into aggressive combined modality treatments for locoregionally advanced disease, and/or its administration as adjuvant to radical surgery. More recently, during the 1990s, a new generation of compounds such as the taxanes (paclitaxel and docetaxel), the topoisomerase inhibitors (irinotecan, topotecan), active analogs (gemcitabine), antimetabolites (pemetrexate), and vinka alkaloids (vinorelbine) were integrated in the treatment of NSCLC. 5 These drugs administered in patients with metastatic disease obtained singleagent activity in the range of 20-30%. When used in combination with other active agents such as the platinums, significant response rates, often in excess of 40%, were reported in pilot phase II studies. The newer agents have been also successfully used in chemotherapy regimens for the treatment of patients with earlier stages of disease as well as in combined-modality treatment programs.