The use of taxanes in early breast cancer

The evidence is now clear that taxanes added to standard adjuvant regimens have acceptable toxicity and can improve outcomes for patients with breast cancer. The North American Intergroup 0 148 study (CALGB 9344) clearly showed a benefit in terms of disease-free survival and overall survival when paclitaxel 175 mg/m(2) was added to adjuvant doxorubicin (A) and cyclophosphamide (C) therapy in 3121 patients with node-positive breast cancer. Adding paclitaxel to AC therapy resulted in a hazard reduction of 17% for recurrence (adjusted Wald chi(2) P = 0.0023) and 18% for death (adjusted Wald chi(2) p = 0.0064). Results from a similar trial, NSABP 1328, in which paclitaxel was also added to standard AC adjuvant therapy and compared with standard AC therapy alone in 3060 patients with node-positive breast cancer are consistent with those of the CALGB trial. This trial also demonstrated a 17% reduction in disease-free survival events (P = 0.008) and a non-significant trend in overall survival when paclitaxel was added. A third large trial (BCIRG 001) testing taxanes as adjuvant therapy comparing 5-fluorouracil plus AC with docetaxel (T) plus AC (TAC vs FAC) yielded a significant improvement in disease-free survival (32% reduction in risk of recurrence, P = 0.0011), as well as a favourable trend in overall survival with the substitution of the taxane in place of 5-fluorouracil. Additional studies in the preoperative setting demonstrate benefits in terms of local tumour response and overall outcomes when taxanes are added to standard therapy. Very recent results suggest that dose-dense administration of chemotherapy including paclitaxel is associated with better outcomes than standard regimens in adjuvant therapy. Hence, the available data are clearly consistent with the hypothesis that taxanes can add to the benefits of existing chemotherapy regimens in the adjuvant setting. Future studies will need to identify subgroups of patients with greater or lesser benefits from taxanes and focus on optimisation of this class of agents. (C) 2003 Elsevier Science Ltd. All rights reserved.