ASCOSubstituting epirubicin for methotrexate in a commonly used
adjuvant regimen significantly increased survival for premenopausal
women with node-negative early-stage breast cancer in a randomized
study by the Danish Breast Cancer Cooperative Group and Swedish
Oncology Centers reported at the American Society of Clinical
Oncology annual meeting.
Henning Mouridsen, MD, of Copenhagen University Hospital, reporting
for the group, said, 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
cyclophosphamide, methotrexate, fluorouracil (CMF) regimen. 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%.
Epirubicin is included in standard treatment regimens for breast
cancer in many countries and is currently being considered for
approval by the FDA. [Epirubicin recently received an FDA advisory
panels recommendation for approval as adjuvant therapy.] Dr.
Mouridsen said the researchers used epirubicin rather than
doxorubicin because studies suggest that the two anthracyclines have
similar efficacy while epirubicin is less cardiotoxic.
The study results concerning epirubi-cin will have a major
impact on the management of breast cancer, Dr. Mouridsen said.
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.
The study included 1,195 pre- and postmenopausal women with
early-stage breast cancer. Following surgery, patients were
randomized to intravenous CMF; intravenous CEF (cyclophosphamide,
epirubicin, fluorouracil); or one of these regimens plus oral
pamidronate. Median follow-up was 61 months, and 1,175 patients were
evaluable. Dr. Mouridsen presented data only on the arms directly
comparing CMF to CEF, without pamidronate (see Table
At 6 years of follow-up, survival of premenopausal women with
node-negative, grade 2-3 tumors was 93% with CEF vs 83% with CMF (P
< .01, Table 2). Survival of all
premenopausal patients was 76% with CEF vs 69% with CMF
(P = .01). Dr. Mouridsen said that this constituted a 23% relative
reduction in mortality with CEF in premenopausal women. There was no
significant advantage for CEF in the subgroup of premenopausal women
with node-positive, receptor-negative or receptor status unknown
tumors, nor were there significant differences between the two
regimens in postmenopausal women.
Therapy was well tolerated, and doses were delivered as scheduled to
96% of women receiving CEF and to 95% of women receiving CMF.
Hematologic toxicities were evenly distributed in the two groups.
There were no instances of congestive heart failure or of leukemia.
However, alopecia occurred in 87% of the CEF group vs only 7% in the
CMF arm. Amenorrhea was induced in 80% of women on CEF vs 60% of
women on CMF.
In premenopausal women, CEF is superior to CMF in terms of
recurrence-free survival and overall survival, but this superiority
is achieved at the cost of hair loss and loss of menstrual
function, Dr. Mouridsen concluded.
During the discussion, a question arose as to whether the increased
efficacy of CEF might not be attributable to the induction of early
menopause. Dr. Mouridsen doubted that this was the case, since
patients with and without amenorrhea achieved the same benefit with
CEF as with CMF. If you look at the total population of
patients with amenorrhea during treatment, they do better than
patients who do not have amenorrhea, but this may also be due to an
interaction with the receptor status, he said. He noted that
recent data from the International Breast Cancer Study Group suggest
that there is no clear effect of chemotherapy-induced amenorrhea when
adjusted for node status, receptor status, and age.