July 29, 2003
Targeted drug combination found effective in treating specific form of metastatic breast cancer
H. Burstein, MD, PhD
A two-drug combination has proved effective and well tolerated in women with a specific form of advanced breast cancer, according to a study led by investigators at Dana-Farber Cancer Institute.
The study, published in the August 1 issue of the Journal of Clinical Oncology, reports the results of a multi-center clinical trial in which women with "HER2-positive" breast cancer (a biologically distinct form of breast cancer in which cells overproduce a growth factor receptor called HER2) were treated with the front-line chemotherapy drug Navelbine (Glaxo Smith Kline; vinorelbine) and the anti-HER2 agent Herceptin (Genentech: trastuzumab). More than two-thirds of the women in the study experienced significant tumor shrinkage with the combination therapy.
The study also describes a strategy for determining which patients are at risk for treatment-related heart failure - a rare but potential complication of Herceptin use - and should therefore be taken off the treatment.
"This trial builds on our previous work suggesting that Herceptin and Navelbine can be highly effective and remarkably well-tolerated for women with advanced, HER2-positive breast cancer," said the study's lead author, Harold Burstein, MD, PhD, of Dana-Farber. "It is gratifying to see confirmation of this experience from clinical centers around the country."
The Herceptin-Navelbine regimen was developed several years ago by Dana-Farber researchers specifically for women with HER2-positive breast cancer, which accounts for 20 to 25 percent of all breast cancer cases. Laboratory studies indicated the two agents would work together in synergy - each enhancing the other's action. The low occurrence of side effects for Navelbine suggested it would be good to pair with Herceptin, which is also well tolerated. The study enrolled 54 women at 17 hospitals from New England and across the United States. All the patients were receiving their first chemotherapy treatment for advanced breast tumors that were highly HER2-positive.
E. Winer, MD
Participants received Herceptin and Navelbine once a week and had their health monitored throughout the study. Thirty-seven of the patients - 68 percent of the entire group - experienced tumor shrinkage, either partial or complete, six months after beginning treatment. Side effects were generally mild, with less than a third experiencing nausea or hair loss.
A substantial minority of the patients - 38 percent - had no worsening of their cancer through one year after starting treatment, although most tumors did eventually begin growing again.
Because of the possible risk of heart damage with Herceptin, researchers monitored the strength of heart function (through a measure known as left ventricular ejection fraction) at the beginning of the study and four months into treatment. They found that patients who were free of heart problems at the four-month timepoint did not develop them later on.
"Monitoring heart function offers a practical way of identifying patients who are, and are not, at risk for treatment-related heart failure as a result of this treatment," Burstein remarks. "The effectiveness of this therapy, and the low incidence of side effects, in treating advanced tumors suggests that it may also be useful for treating earlier stages of the disease. We are now exploring the use of this regimen as treatment for early-stage breast cancer."
Senior author of the study was Eric Winer, MD, of Dana-Farber. Other contributors are based at Duke University; South Carolina Oncology Associates; Evanston Hospital, Evanston, Ill.; University Hospitals of Cleveland; New Hampshire Hematology-Oncology; Capital District Hematology/Oncology, Latham, N.Y.; Miriam and Rhode Island Hospitals, Providence, R.I.; the Cancer Research Network of Plantation, Fla.; and Massachusetts General Hospital.
Dana-Farber Cancer Institute is a principal teaching affiliate of the Harvard Medical School and is among the leading cancer research and care centers in the United States. It is a founding member of the Dana-Farber/Harvard Cancer Center (DF/HCC), designated a comprehensive cancer center by the National Cancer Institute.
