乳腺癌 FEC vs FEC-D

FIVE-YEAR RESULTS FROM PACS 01 Trial Show Advantage for
Women Over 50
r. Henri Roché reported that the addition of three cycles of
docetaxel to three cycles of standard FEC100 chemotherapy
results in
significantly improved disease-free survival in older
women
, compared to six cycles of FEC100. The combination

therapy also has the advantage of a better side-effect profile.
As of 1997, FEC100 (5-fluorouracil, epirubicin, and
cyclophosphamide, with epirubicin at a dose of 100 mg/m2)
was considered to be the standard adjuvant treatment for breast
cancer in France. The PACS 01 trial was designed to evaluate the
impact of the sequential addition of docetaxel to FEC100 on
disease-free survival. The study was open to women with
operable, node-positive, unilateral breast cancer. Patients were
stratified by study center, age (< or > 50), and nodal status (N
= 1-3 or N >3). Patients in study arm A received 6 cycles of
FEC100, with one cycle given every 21 days. Patients in study
arm B received three cycles of FEC100 followed by three cycles
of docetaxel, with one cycle given every 21 days. Radiotherapy
was given four weeks after the completion of the last
chemotherapy cycle. Tamoxifen was given for five years after
the completion of chemotherapy. The primary endpoint
of the study was disease-free survival. At five years, there was a
significant difference in disease-free survival between the two

study arms,
with an absolute difference of 5.1% in favor of

FEC100–docetaxel
(HR = 0.83, P = 0.041). Additional analyses
looked at the interaction with nodal status and age. When
patients were grouped for number of positive nodes (1-3
positive nodes versus >3 positive nodes),
there was a significant
benefit to FEC100–docetaxel in the 1-3 node group but not in
the >3 node group. There was also a significant interaction with
age, with the survival advantage specific to women over the age
of 50, and no advantage seen in women younger than 50.
These findings are unexpected and difficult to explain, as
chemotherapy regimens have more typically tended to favor
younger women. In French women over 50, approximately
25% are nonmenopausal, making this is a heterogeneous group
in terms of hormonal environment.
The number of first events, distant relapse events, and deaths
were all significantly higher in the FEC100 group compared with
the FEC100–docetaxel group The FEC100-docetaxel regimen
was also well tolerated. Women receiving the sequential
therapy experienced significantly fewer cardiac events, less
neutropenia at day 21, less cycle delay, and less use of G-CSF, in
spite of a higher rate of febrile neutropenia. Edema and nail
disorders were more frequent than in the FEC100 arm. The
PACS 04 trial, which has just closed, is comparing FEC100 with
combined, rather than sequential, FEC100–docetaxel. Other
trials are planned to directly compare sequential and
combination docetaxel-containing regimens, and to investigate
a longer duration and/or dose dense treatment specifically for
premenopausal women.