Treatment of patients resistant to paclitaxel therapy

Although the taxoid drugs, paclitaxel (Taxol®) and docetaxel (Taxotere®) have a broadly similar mechanism of action, there are notable differences in their activities and they are distinct agents. Docetaxel is more potent than paclitaxel with regard to the promotion of the polymerization of tubulin and the inhibition of depolymerization, and has greater antitumour activity in many in vitro and in vivo tumour model systems. The development of drug resistance is a major problem in the treatment of metastatic breast cancer and observations indicating only partial cross-resistance between docetaxel and paclitaxel in vitro, combined with supporting clinical evidence of activity in patients with previously-treated tumours, including anthracycline-resistant breast cancer, led to the implementation of a prospective study of docetaxel treatment in patients with paclitaxel-resistant disease. Preliminary results in 27 patients recruited to this ongoing study indicate that docetaxel has activity in paclitaxel-resistant metastatic breast cancer.