The role of taxanes in the adjuvant treatment of early stage breast cancer.
Adjuvant chemotherapy plays a significant incremental role in improving survival in patients with early stage breast cancer. Survival benefits gained in the adjuvant setting with anthracycline-based polychemotherapy regimens are now level- 1 evidence based, and in an attempt to further these gains, many randomized trials are examining new treatment options. Other important goals include defining the magnitude of benefit with current and investigational regimens in prospectively defined risk groups. The taxanes, docetaxel and paclitaxel, are under investigation in the adjuvant setting in a large series of randomized clinical trials that will enroll not less than 56,000 women, among whom 22,000 women will contribute to paclitaxel-related questions and 34,000 to docetaxel-related questions. The main focus of this review will be the first-generation trials (N = 31,000), which include at least one non-taxane arm. For the most part, trials with paclitaxel have evaluated the agent in sequence with anthracycline-based therapy, while trials with docetaxel are evaluating it as an alternative to one of the standard drugs in a combination regimen as well as in sequence with anthracycline-based regimens. To date, results from four randomized trials with adjuvant paclitaxel and two with docetaxel have been presented. All reports but one are based on interim analyses. Only one of the paclitaxel trials so far demonstrated a statistically significant improvement in disease-free and overall survival relative to the comparator, while a second trial demonstrated superiority of dose-dense chemotherapy over conventional dosing. Interim results with docetaxel suggest that substituting docetaxel for fluorouracil in combination with doxorubicin and cyclophosphamide results in improved disease-free survival, with a trend toward improved overall survival. Completion of ongoing trials and maturation of the current data will further define the role of taxanes in the adjuvant treatment of early stage breast cancer.
Piccart
Martine
M
Chemotherapy Unit, Jules Bordet Institute, Brussels, Belgium. martine.piccart@bordet.be
D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D000077143:Docetaxel; D005260:Female; D006801:Humans; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D016032:Randomized Controlled Trials as Topic; D016019:Survival Analysis; D043823:Taxoids
D000972:Antineoplastic Agents, Phytogenic; D043823:Taxoids; D000077143:Docetaxel; D017239:Paclitaxel