Single agents in the second-line treatment of non-small cell lung cancer

Abstract

The options available to patients with advanced non-small cell lung cancer (NSCLC) resistant or refractory to first-line chemotherapy are very limited. The older-generation drugs (etoposide, vindesine, epirubicin, and cisplatin) that are active against previously untreated NSCLC do not achieve a response rate greater than 10% when used in the second-line setting. The newer-generation agents with activity in previously untreated NSCLC include carboplatin, paclitaxel, docetaxel, vinorelbine, gemcitabine, and irinotecan. Although NSCLC remains relatively resistant to chemotherapy, the fact that second-line chemotherapy is being considered is tribute to the progress being made with first-line therapy. The taxanes have clearly become the agents of the 1990s. The activity of paclitaxel in the second-line setting is not well-defined, and the response rates have ranged from 0% to 3 31% using various schedules. However, docetaxel achieved response rates of 15% to 22% in five phase II trials, with a clinically meaningful survival rate of 25% at 1 year in one of the studies. Randomized trials of docetaxel versus best supportive care and of docetaxel versus vinorelbine or ifosfamide are in progress. The efficacy of vinorelbine and irinotecan in the second-line setting have been dismal. Gemcitabine demonstrated a response rate of 25% in a recently reported trial and needs further investigation. Further progress may come from a wider investigation of novel agents and their combination with biological and other selective therapies.