Docetaxel (Taxotere) in HER-2-positive patients and in combination with trastuzumab (Herceptin).

In addition to being an important indicator of poor prognosis, human epidermal growth factor receptor-2 (HER-2) status may help identify those patients in whom chemotherapy is the most appropriate choice of therapy. In several studies, including a trial of sequential neoadjuvant therapy in which certain patients received docetaxel (Taxotere; Rhône-Poulenc Rorer, Antony, France) following four courses of cyclophophamide 1000 mg/m2, doxorubicin 50 mg/m2, vincristine 1.5 mg/m2 on day one, and prednisone 40 mg by mouth for 5 days, HER-2 positivity predicted response (including pathologic response) to chemotherapy. In vitro and in vivo, docetaxel has demonstrated true synergy with the recombinant human anti-HER-2 monoclonal antibody trastuzumab (Herceptin; Genentech, San Francisco, CA). In a phase III study comparing trastuzumab alone with trastuzumab plus chemotherapy (either paclitaxel or doxorubicin plus cyclophosphamide), combining the antibody with cytotoxic drugs increased response duration, time to progression, and survival in first-line metastatic breast cancer patients. Preliminary clinical data suggest that the combination of trastuzumab with docetaxel is active and well tolerated, and pilot studies of adjuvant therapy using trastuzumab and docetaxel combinations are under way in high-risk patients.