Combinations of docetaxel, cisplatin or carboplatin, and the monoclonal antibody trastuzumab are feasible for the treatment of patients with HER2-positive advanced breast cancer in which tumor response rates are high, according to two new studies.

Human epidermal growth factor receptor 2 (HER2) is overexpressed in the tumors of 20-30% of breast cancer patients and is associated with an increased risk of relapse and death in patients with early-stage breast cancer. In earlier clinical trials, adding trastuzumab, which blocks the effects of HER2, to standard chemotherapy increased both the response rate of patients and survival, but an unacceptable number of patients experienced cardiac dysfunction, including congestive heart disease.

In the first of two studies designed to find safer chemotherapy combinations that include trastuzumab, Mark D. Pegram, M.D., of the University of California, Los Angeles, and colleagues characterized the interactions between trastuzumab and nine chemotherapy drugs commonly used in treating breast cancer in four cell lines that overexpress HER2. They found synergistic interactions of trastuzumab plus carboplatin, 4-hydroxycyclophosphamide, docetaxel, or vinorelbine, which indicated that these were reasonable combinations to test in human clinical trials.

In the second study, a second group of researchers also led by Pegram, conducted two phase II clinical trials to evaluate the combination of docetaxel and trastuzumab with either of two platinum salts, cisplatin or carboplatin. In each trial, the combinations were tested on 62 women with advanced breast cancer that overexpressed HER2. Both combinations had a similar toxicity to docetaxel plus platinum salts alone, and there was a low incidence of cardiac dysfunction. In addition, overall response rates were higher. The combinations are now being tested
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Contact: Sarah L. Zielinski
jncimedia@oupjournals.org
301-841-1287
Journal of the National Cancer Institute
18-May-2004