Future developments for paclitaxel in the treatment of breast cancer

Several clinical studies worldwide have demonstrated clearly the remarkable activity of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) in treating metastatic breast cancer. Future directions should focus on two strategic points: the optimal combination of paclitaxel with other cytotoxic drugs and the most appropriate time to administer a paclitaxel-containing combination. The Milan experience using doxorubicin plus paclitaxel indicated an objective response rate of 95% (complete remissions, 41%) among chemotherapy-naive patients with disseminated breast cancer. This very high response rate was recently confirmed in a study involving 12 women with primary inoperable disease (stage IIIB). To avoid cardiac effects, only four treatment cycles were used; the excellent tumor shrinkage was followed by mastectomy. Since no signs of myocardial toxicity were detected, we are currently testing the same drug schedule in women with smaller breast tumors (eg, 2.5 to 5.0 cm largest diameter) in an attempt to increase the frequency of pathologic complete remission following breast-conserving surgery. Thus, future research programs should exploit the efficacy of paclitaxel plus doxorubicin (or epirubicin) in the early stages of breast cancer. In turn, such studies should enable research physicians to build up more effective strategies with preoperative (neoadjuvant) and postoperative (adjuvant) breast cancer treatments.