First Clinical Trial Opens to Study Antibody for Treatment of Early Breast Cancer

The University of Texas M.D. Anderson Cancer Center has opened the first clinical trial to study a new therapy that enhances the effectiveness of the standard regimen of chemotherapy in early-stage, preoperative breast cancer.

Herceptin, the new therapy, is a monoclonal antibody-an antibody derived from a single cell in large quantities for use against cancer. Herceptin has proven successful when administered with chemotherapy in the treatment and stabilization of metastatic breast cancer, says Dr. Aman Buzdar, professor in M.D. Anderson’s Department of Breast Medical Oncology and principal investigator of the study. This will be the first time that it will be administered in earlier-stage breast cancer, prior to surgical procedures.

Under M.D. Anderson’s Department of Breast Medical Oncology, this Phase III clinical trial is recruiting 164 women with untreated breast cancer tumors that express the human epidermal growth factor receptor known as Her2/neu. Researchers are conducting the trial to learn if the addition of Herceptin to standard chemotherapy regimen can shrink breast tumors to reduce the need for invasive surgery and reduce the risk of recurrence.

Research has shown that 25 to 30 percent of women with breast cancer over-express the Her2/neu gene. The disease often recurs in patients who express this gene, and are statistically more likely to die from breast cancer than those who do not express Her2/neu.

"We are initially studying Herceptin as an early-phase treatment in patients who have an unfavorable prognosis in beating their disease simply because of the makeup of their tumors’ genes," says Dr. Buzdar. "With the addition of Herceptin to standard neoadjuvant chemotherapy regimen prior to surgery, we hope to downstage the size of the primary tumor, possibly reducing the need for a major breast surgery, such as a mastectomy, in favor of a less-invasive surgery option. We also want to see if this combination decreases the risk of local recurrences."

Dr. Buzdar explains that one of the benefits of administering Herceptin as a neoadjuvant therapy prior to surgery, rather than post-surgery, is that researchers can determine much faster if there is a benefit to adding this drug to the standard chemotherapy regimen.

"If we were administering Herceptin after surgery, we would have to wait decades to know if the treatment was effective," says Dr. Buzdar. "By administering prior to surgery, we should have a good idea, once all of these women have finished the 24-week regimen, if Herceptin is a successful addition to the standard therapy."

The randomized study will compare patients on chemotherapy and Herceptin to patients on the chemotherapy alone. All participants will receive the standard preoperative chemotherapy 24-week regimen given to Her2/neu-positive women. This includes 12 weeks (four cycles) of Taxol and the three-drug combination of 5-Fu, Epirubicin and Cytoxan, known as FEC. Simultaneous with this chemotherapy regimen, half of the women enrolled in the trial also will receive Herceptin. Throughout the chemotherapy regimen, participants will receive mammograms and physical examinations to monitor tumor size. Following the 24 weeks, all participants will undergo surgery. Surgical options will be determined by the size of the tumor after chemotherapy.

"We already know that the Taxol and FAC combination shrinks breast tumors to some extent in 80 percent of women who are Her2/neu-positive," says Dr. Buzdar. "By including Herceptin in this drug regimen, we want to learn if we can shrink the tumor in a larger percentage of these patients and if the tumor itself shrinks even smaller, possibly disappearing altogether."

One known risk associated with Herceptin is damage to the heart muscle, a condition Dr. Buzdar says can be repaired in a majority of patients.

To minimize the potential for any such risk, prospective patients will receive a baseline echocardiogram prior to trial enrollment to determine that they have normal cardiac function. Patients’ heart function will be monitored throughout the protocol and blood tests will also be administered on a routine basis.

Bristol Myers Squibb, Genentech Inc. and Pharmacia Upjohn are sponsoring the Phase III trial. Prospective participants and/or referring physicians who would like to learn more about the study, as well as additional inclusion requirements, should call (713) 792-4124 or The M.D. Anderson Information Line at 1-800-792-1611.

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©2006 Texas Medical Center

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