Docetaxel for locally advanced or metastatic non-small-cell lung cancer. Current data and future directions as front-line therapy.
Docetaxel (Taxotere) has shown activity both as a single-agent and in combination with multiple other cytotoxic agents in the front-line therapy of advanced, metastatic non-small-cell lung cancer (NSCLC). A randomized, phase III trial demonstrated a survival advantage for docetaxel over best supportive care in the front-line setting, with docetaxel achieving a 2-year survival of 12% vs 0% for best supportive care. Combinations of docetaxel with the platinum agents have been the most extensively studied in the front-line setting and have produced notably high response rates and encouraging median survivals. When compared to the paclitaxel/cisplatinum combination in a large, phase III randomized trial, the combination of docetaxel and cisplatin resulted in similar response, median survival, and 1-year survival rates. Another randomized phase III trial compared docetaxel/platinum combinations to the US Food and Drug Administration (FDA)-approved vinorelbine (Navelbine)/cisplatin regimen. The docetaxel/cisplatin combination produced a superior overall survival, 2-year survival, and overall response rates compared to vinorelbine/cisplatin. The combination of docetaxel and carboplatin (Paraplatin) demonstrated similar survival and response, and was associated with quality-of-life benefits over the vinorelbine/cisplatin arm. Docetaxel has been successfully combined with gemcitabine in multiple trials with impressive response and survival rates, and an acceptable toxicity profile. A large phase IIb trial demonstrated therapeutic equivalence and lesser toxicities for the docetaxel/gemcitabine combination compared to the combination of docetaxel and cisplatin. The docetaxel/gemcitabine combination therefore represents a viable nonplatinum regimen for first-line treatment of NSCLC. Other combinations that have been tested include docetaxel with vinorelbine, and docetaxel with irinotecan (CPT-11, Camptosar). Docetaxel is active in NSCLC and should be investigated further in combination with novel molecularly targeted drugs such as tyrosine kinase inhibitors, andfarnesyl transferase inhibitors.
Department of Thoracic/Head and Neck Medical Oncology, The University of Texas, M.D. Anderson Cancer Center, Houston 77030, USA. fkhuri@mail.mdanderson.org
Fadlo R
FR
Khuri
D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D002986:Clinical Trials as Topic; D000077143:Docetaxel; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D011788:Quality of Life; D043823:Taxoids
D000972:Antineoplastic Agents, Phytogenic; D043823:Taxoids; D000077143:Docetaxel; D017239:Paclitaxel