Introducing taxanes in the adjuvant treatment of breast cancer: expectations and reality.
Adjuvant chemotherapy in early breast cancer significantly improves disease-free and overall survival. However, a recent update of the world-wide overview indicated that improvements, though statistically significant, are of modest magnitude. Considering the results of individual clinical trials, further improvements in disease-free survival through introduction of new drugs as part of adjuvant treatment for breast cancer are expected to be small. Phase III studies in advanced, measurable disease, each involving several hundreds of patients, have been conducted with both paclitaxel and docetaxel and these results are now available. The high level of efficacy observed, especially with docetaxel, has led to their prompt introduction into adjuvant trials, and the results of one trial with paclitaxel are already available. In this trial, which included 3170 patients, paclitaxel was given every three weeks for four courses following an adjuvant treatment with four courses of doxorubicin and cyclophosphamide (AC) combination. The sequential use of the AC following by the taxane showed an early significant improvement of disease-free survival as compared to AC alone, but the difference observed was exclusively in the 40% of patients who had oestrogen receptor (OR)-negative disease. These patients, and a few of those with OR-positive primaries, did not receive tamoxifen following chemotherapy. Differences in duration of the entire adjuvant treatment programme might have influenced results leading to potentially the wrong conclusion being drawn that the taxane made the difference and other treatment variables had a negligible influence on outcome. Taxanes deserve a 'fair trial' in the adjuvant setting. Moreover, potential cardiotoxicity and long-term impact of high-dose steroids suggest that caution and longer follow-up are required before the definitive introduction of taxanes into the routine care of patients with early breast cancer.
Colleoni
M
M
Division of Medical Oncology, European Institute of Oncology, Milan, Italy. marco.colleoni@ieo.it
Orlando
L
L
Nole'
F
F
Goldhirsch
A
A