Taxoids: effective agents in anthracycline-resistant breast cancer

The results of recent clinical trials have shown that docetaxel (Taxotere; Rhône-Poulenc Rorer, Antony, France), like paclitaxel (Taxol; Bristol-Myers Squibb Oncology, Princeton, NJ), has high levels of activity in patients with anthracycline-resistant breast cancer. Agents that are at least partially non-cross-resistant with anthracyclines are especially promising for the treatment of breast cancer; the taxoids (docetaxel and paclitaxel) are such agents. Although preclinical evaluations shows clear instances of strong cross-resistance (particularly in cells lines expressing the P-glycoprotein, multidrug resistance), high response rates have been reported in patients with prior anthracycline exposure and/or anthracycline resistance. Phase I studies of anthracycline and taxoid combinations have been conducted. Excellent response rates have been noted in some of these studies. In some studies using regimens combining doxorubicin and paclitaxel, unanticipated toxicities have occurred, such as typhlitis, as well as congestive heart failure at lower than expected cumulative doses of doxorubicin. Phase II and III studies of regimens including both anthracyclines and taxoids have been initiated. Docetaxel and paclitaxel appear to be valuable agents for use in anthracycline-resistant breast cancer patients, and may find a place in anthracycline-containing combination regimens.