Development of docetaxel in advanced non-small-cell lung cancer

Abstract

Docetaxel, a semisynthetic taxane initially developed for the treatment of breast cancer, has a high degree of activity in lung cancer. Although the mechanisms of action of the taxanes docetaxel and paclitaxel are identical, docetaxel has almost a twofold higher binding affinity for the target site, beta tubulin. In clinical trials, individuals previously treated with paclitaxel benefited from docetaxel. Docetaxel is the standard of care in second-line therapy of advanced non-small-cell lung cancer (NSCLC) and is effective, alone and in combination, in first-line treatment of advanced NSCLC. The standard in first-line therapy of metastatic NSCLC is a platinum doublet with one of the third-generation chemotherapy agents, docetaxel, paclitaxel, gemcitabine, or vinorelbine. Each of these doublets offers similar therapeutic benefit. In a phase-III study comparing docetaxel-cisplatin and docetaxel-carboplatin with vinorelbine-cisplatin, patients treated in the two docetaxel arms had consistently improved global QoL compared to patients treated with the vinorelbine-cisplatin doublet. This landmark study led to Food and Drug Administration (FDA) approval of cisplatin-docetaxel for the treatment of advanced NSCLC. Non-platinum doublets such as docetaxel-gemcitabine have also demonstrated efficacy and safety. Docetaxel has undergone extensive evaluation and is the only agent approved for use in both first- and second-line therapy of advanced NSCLC.