Anthracyclines and taxanes are commonly used chemotherapy agents in the adjuvant treatment of early breast cancer. Anthracyclines are usually administered before taxanes (or combined with taxanes), a practice which reflects the sequence of administration used in clinical trials rather than research-based evidence. However, recent data suggest that the administration of a taxane first, followed by an anthracycline, may be preferable in line with the Norton-Simon hypothesis.
At least six randomized studies have investigated the optimum sequence of anthracycline and taxane administration in the adjuvant or neoadjuvant setting. Three out of four adjuvant trials found that the taxane-first regimens were favourable in terms of the relative drug dose intensity achieved. Larger, nonrandomized adjuvant studies lend support to these observations. In a series of 284 patients who first received three cycles of FEC (fluorouracil, epirubicin and cyclophosphamide) followed by three cycles of docetaxel, the mean relative dose intensity was 91% for FEC and 76% for docetaxel, whereas in another series of 378 patients who received three cycles of docetaxel followed by four cycles of EC (epirubicin plus cyclophosphamide), a median docetaxel dose intensity of 100% was achieved.