Docetaxel in combined-modality treatment of inoperable locally or regionally advanced lung cancer

Abstract

Although most clinicians use a combination of a platinum-containing regimen and radiation therapy to treat non-small-cell lung cancer (NSCLC), there is no reference regimen for inoperable stage-III NSCLC. Limited phase-III data suggest concurrent chemoradiotherapy is preferable to sequential therapy. Combined-modality chemoradiotherapy with cisplatin plus agents such as vindesine, mitomycin C, vinblastine, etoposide, vinorelbine, or paclitaxel yield a median survival of only 15-17 months, with distant metastases being the most common reason for failure. The need for new therapeutic approaches to target distant metastases is a critical issue. In addition to its proven antitumor properties in NSCLC, docetaxel has radiosensitizing activity, making it well-suited for use in combined-modality regimens. Several phase-I/II studies have demonstrated that concurrent docetaxel, cisplatin, and radiation therapy is a feasible regimen, yielding objective response rates of 70-90%. A regimen of cisplatin plus docetaxel induction followed by thoracic radiotherapy plus docetaxel resulted in an objective response of 58% in a phase-II trial. A second phase-II trial evaluating a unique regimen of chemoradiotherapy using cisplatin and etoposide followed by consolidation docetaxel yielded a median survival of 26 months. This compares favorably to historical data demonstrating a median survival of 15 months using cisplatin, etoposide, and radiation therapy without consolidation docetaxel. Phase-III research is currently underway to confirm the favorable phase-II results with docetaxel.