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Drug combo effective in advanced breast cancer

A pair of studies at UCLA's Jonsson Cancer Center taking laboratory science to the patient bedside found that combining the molecularly targeted therapy Herceptin with a specific chemotherapy combination resulted in significant tumor response rates and longer relapse-free periods in women with an aggressive form of advanced breast cancer.

The results of the studies, the first done on cell lines in the laboratory and the second translated into more than 120 patients in two Phase II clinical trials, appear Tuesday (May 18) in the peer-reviewed Journal of the National Cancer Institute.

In an accompanying editorial, Dr. George W. Sledge, Jr., co-director of the Breast Cancer Program at the Indiana University School of Medicine, called the studies "an impressive example of translational research at its best."

"Designing a sequential series of experiments, both laboratory and clinical, that lead intentionally to proof-of-concept adjuvant (Phase III) trials is all too rare," Sledge states in the editorial. "But, as (UCLA researchers) remind us, it is not impossible."

Jonsson Cancer Center researchers first tested drug combinations in the laboratory with the goal of translating their results into patients with HER2/neu amplification, a genetic alternation found in 20 to 25 percent of patients that leads to an aggressive form of breast cancer.

Lead by researchers Dr. Dennis Slamon and Dr. Mark Pegram, the laboratory studies analyzed Herceptin for interaction with nine chemotherapy drugs commonly used to treat breast cancer. Researchers found that the chemotherapy agents Taxotere, Navelbine, Cyclophosphamide and the platinum salts Cisplatin and Carboplatin increased the activity of Herceptin in lab models with HER2/neu amplification. In other words, Herceptin and the chemotherapy agents each made the other more effective, a synergistic effect. The laboratory studies pointed researchers to the optimum chemotherapy combination, which
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Contact: Kim Irwin
kirwin@mednet.ucla.edu
310-206-2805
University of California - Los Angeles
18-May-2004


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