Trastuzumab in combination with chemotherapy for the treatment of metastatic breast cancer.

Overview

Metastatic breast carcinoma still remains an incurable condition. The relentless search for novel agents that might prove useful for management has evolved toward monoclonal antibodies, in part because of a rapidly expanding understanding of breast cancer biology. Trastuzumab (Herceptin; Genentech, Inc, South San Francisco, CA) is a recombinant humanized monoclonal antibody against the HER-2 receptor that has shown antitumor activity as a single agent in phase I and II trials of patients with metastatic breast cancer overexpressing HER-2. The observation of increased antitumor activity between trastuzumab and some chemotherapeutic agents in preclinical models has prompted its use in combination with several drugs. Of particular interest is the use of trastuzumab with paclitaxel. Two trials were presented at the 1999 meeting of the American Society of Clinical Oncology that evaluated this combination. One multicenter phase III trial showed clinical benefit and increased survival for patients with HER-2-overexpressing metastatic breast cancer treated with chemotherapy plus trastuzumab. A phase II trial, reviewed in this report, evaluated the efficacy and safety of weekly paclitaxel plus trastuzumab for patients with metastatic breast carcinoma, including those overexpressing and nonoverexpressing HER-2.