Docetaxel (taxotere) plus trastuzumab (herceptin) in breast cancer

The rationale for the combined use of docetaxel (Taxotere; Aventis Pharmaceuticals, Inc, Parsippany, NJ) and trastuzumab (Herceptin; Genentech, South San Francisco, CA) in HER2/neu-overexpressing breast cancer patients are several-fold. Docetaxel is a highly active chemotherapeutic agent in metastatic breast cancer. Response rates, time to progression, and survival are improved when trastuzumab is combined with chemotherapy. Finally, preclinical findings demonstrate synergistic cytotoxic activity when docetaxel and trastuzumab are combined. In addition, their different mechanisms of action and a nonoverlapping toxicity profile suggest the potential for a highly useful combination while minimizing potential cardiotoxicity. An ongoing pilot phase II evaluation is being conducted with every-3-week docetaxel plus weekly trastuzumab. Preliminary findings suggest an active and well-tolerated regimen. Efficacy data indicate an encouraging overall major response rate of 45% in first- and second-line metastatic breast cancer patients. Preliminary results from a second phase II trial of weekly docetaxel and trastuzumab have been reported. In 14 patients treated to date, grade (3/4) toxicities are infrequent. An overall response rate of 54% is reported thus far with 26 cycles (156 weeks) of therapy delivered. The preliminary data for the docetaxel and trastuzumab combinations look favorable from both a safety and an efficacy perspective. The lack of cardiac function changes despite frequent cardiac monitoring is promising. For the adjuvant therapy of HER2/neu-overexpressing breast cancer, the high level of efficacy of docetaxel and the need to identify nonanthracycline agents for combined use with trastuzumab place a high emphasis on the potential utility of docetaxel and trastuzumab-based regimens.