Adjuvant chemotherapy: Controversies and the role of taxanes

The role of taxanes as adjuvant breast cancer therapy continues to evolve. In the first reported randomized trial (CALGB 9344) paclitaxel was evaluated in sequence to AC (doxorubicin/cyclophosphamide). This trial demonstrated a statistically significant improvement in disease free survival and a non-significant improvement in overall survival for patients randomized to paclitaxel. There was a suggestion that the benefit from paclitaxel was mainly seen in patients with receptor-negative tumors. Mature results from a second trial of similar design (NSABP B-28) are not available yet. A recently reported trial comparing the triple combination TAC (docetaxel/doxorubicin/cyclophosphamide) to FAC (5 fluorouracil/doxorubicin/cyclophosphamide) has also demonstrated a statistically significant improvement in disease-free survival and a non-significant improvement in overall survival for patients randomized to the TAC regimen. In that trial the benefit was seen irrespective of receptor status and was more pronounced in patients with 1-3 positive nodes. In the neoadjuvant setting, several randomized trials have shown that the sequential administration of taxanes after an anthracycline/cyclophosphamide-containing regimen can significantly improve pathologic complete response (pCR) rates in the breast and can downstage involved axillary nodes. Since achievement of pCR following administration of anthracyline-containing chemotherapy regimens has been significantly correlated with improved outcome, it is hoped that the increase in pCR rates seen with the sequential addition of taxanes will translate to an overall survival improvement. However, such results are not available yet.