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
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 treatments 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%
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
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.
*Editors Note: Since the ASCO meeting, epirubicin has
received approval in the United States for the treatment of breast cancer.