Epirubicin Regimen Cuts Risk of Death in Premenopausal Women With Early Breast Cancer

Premenopausal women with early breast cancer have a significantly better chance of living longer when treated with a chemotherapy regimen that includes epirubicin (Ellence), as opposed to a current standard combination regimen, according to data presented at the 35th meeting of the American Society of Clinical Oncology (ASCO).

In a large phase III study involving more than 1,000 women, researchers demonstrated that adjuvant treatment with the CEF regimen (cyclophosphamide, epirubicin, and fluorouracil) improved 6-year survival rates in premenopausal women with node-negative, grade 2-3 tumors. Patients treated with the epirubicin combination achieved a survival rate that was 10% higher (93% vs 83%; P < .01) than the rate achieved with the commonly used drug combination CMF (cyclophosphamide, methotrexate, and fluorouracil).

“This study shows that an epirubicin-based regimen offers highly significant disease-free and overall survival advantages for premenopausal breast cancer patients compared to a CMF regimen,” said Dr. Henning Mouridsen, principal trial investigator and general secretary at the Danish Breast Cancer Cooperative Group, Copenhagen University Hospital, Denmark. “By using the epirubicin-based regimen instead of CMF, we can decrease the risk of death from breast cancer in premenopausal women by approximately 20% to 25%.”

“The epirubicin combination and CMF are standard treatments around the world, so this study is of special importance,” said Dr. Mouridsen. “Although 10-year data will offer a true test of the treatment’s success, the 6-year survival data is very promising.”

Clinical Trial Design

The trial followed 1,195 premenopausal and postmenopausal women with early breast cancer for 6 years. Enrollees fell into one of three subgroups: premenopausal women with node-negative, grade 2-3 tumors (subgroup A); premenopausal women with node-positive, receptor-negative or receptor-unknown tumors (subgroup B); and postmenopausal women with node-positive, receptor-negative tumors (subgroup C). Following surgery, patients were randomly assigned to receive first-line chemotherapy with either CMF or CEF.

After 6 years, the combined overall survival rate in epirubicin-treated women from subgroups A and B was 76%, compared to 69% (P < .01) for those given the CMF combination. (A 24% death rate for the CEF arm compared to a 31% death rate for the CMF arm results in an absolute mortality reduction of 7% and a relative reduction of approximately 20% to 25%.) In subgroup A, women treated with CEF had a survival rate of 93%, while those receiving CMF had a survival rate of 83% (P < .01). Women in subgroup B who were treated with CEF had a survival rate of 66% vs a 60% survival rate for those given CMF. No statistically significant difference in survival rates between treatments was observed in subgroup C (50% vs 48%).

Toxicities Evenly Distributed

Hematologic toxicities were evenly distributed in the two groups. Side effects that occurred more frequently in the CEF group included transient hair loss (87% vs 7%) and loss of menstrual function (80% vs 60%).

“The study results concerning epirubicin will have a major impact on the management of breast cancer,” said Dr. Mouridsen. “Except in the United States, where epirubicin has not yet been approved,* women with early breast cancer are generally treated with a regimen based on either epirubicin or methotrexate. This study shows that epirubicin may be the better treatment option for premenopausal women.”

In the United States, two standard chemotherapy regimens, CMF and CAF (cyclophosphomide, Adriamycin, and fluorouracil), have demonstrated similar survival rates when used as adjuvant treatment.

*Editor’s Note: Since the ASCO meeting, epirubicin has received approval in the United States for the treatment of breast cancer.