Docetaxel (Taxotere) for the treatment of anthracycline-resistant breast cancer.

Until the introduction of the taxoids, docetaxel (Taxotere; Rhône-Poulenc Rorer, Antony, France) and paclitaxel (Taxol; Bristol-Myers Squibb Oncology, Princeton, NJ), in the 1990s, anthracyclines were widely recognized as the best single agents for the treatment of breast cancer. However, even when anthracyclines are used in combination regimens with response rates of over 50%, including complete responses in 17% of patients, few women (3%) with metastatic disease remain disease free at 5 years after treatment. The low level of sustained responses is largely due to the phenomenon of drug resistance. Anthracycline resistance often involves multidrug resistance efflux mechanisms, but also can involve factors affecting topoisomerase II and apoptosis. When combining other cytotoxic agents with anthracyclines, it is of value to use non-cross-resistant drugs so that the induction of anthracycline-resistance mechanisms does not also affect the efficacy of other agents in the combination therapy. Clinical studies have shown that docetaxel, which is highly active against metastatic breast cancer as a single agent, has a high level of non-cross-resistance with anthracyclines. The overall response rate to docetaxel monotherapy in patients with anthracycline-resistant or refractory metastatic disease has been shown to be 41%. The response rate to first-line docetaxel monotherapy for metastatic breast cancer has been shown to be 61%, suggesting that two thirds of the activity of docetaxel is retained in anthracycline-resistant disease. Treatment with a simultaneous combination of docetaxel and doxorubicin has been found to be very active, with a response rate of 89%, and trials to exploit the lack of cross-resistance between these agents, in sequential regimens and adjuvant therapies, are under way.