More frequent dosing of chemotherapy for breast cancer can significantly improve survival without increasing toxicity
More frequent administration of chemotherapy
can lead to a 31 percent decrease in mortality among women with node-positive
breast cancer without increasing drug toxicity, according to study
results presented at the 25th Annual Breast Cancer Symposium.
“Since breast cancer is so common, and adjuvant
drug therapy has already been found to be so effective, a way to
make that treatment 31 percent more effective could potentially
save thousands of lives per year in the United States alone,” said
Larry Norton, M.D., senior author.
The question, “Is it better to use a higher dose of a drug less
often or a lower dose more often?” was the basis for the two types
of regimens studied, dose-dense and sequential therapy compared
with conventionally timed and concurrent therapy, respectively.
The study enrolled 2,005 women with primary breast cancer with lymph
node involvement but no other metastases. Women were randomized
postoperatively to one of four treatments: doxorubicin, paclitaxel,
and cyclophosphamide sequentially in either a 2-week or 3-week cycle
or concurrent doxorubicin and cyclophosphamide followed by paclitaxel
in either a 2-week or 3-week cycle.
Because of the risk of neutropenia, women
on dose-dense regimens received granulocyte colony stimulating factor
to permit drug cycles of 2 weeks rather than the conventional 3
weeks.
After 4 years of follow-up, researchers found that the dose-dense
(2-week) regimens, whether sequential or concurrent, were significantly
better than conventional (3-week) regimens in improving both disease-free
and overall survival. Among patients on dose-dense regimens, disease-free
survival was 82 percent compared with 75 percent for women who received
conventional therapy. At 3 years of follow-up, there was 92 percent
survival for patients on dose-dense therapy compared with 90 percent
for patients on conventionally timed regimens. The differences in
effect between dose-dense and conventional regimens were expected
to increase over time with continued patient follow-up.
Researchers found that side effects were no more severe among patients
on dose-dense regimens than among those on conventional regimens.
In addition, patients on dose-dense regimens suffered fewer cases
of neutropenia.
“These findings are significant because all
the women received the same individual and cumulative dosage of
each drug--the only difference was the interval between chemotherapy
treatments--and that one difference is shown to make a positive
impact on survival,” said lead author Marc L. Citron, M.D.
“The idea of dose density is really rather
simple: give the drugs more often and don’t give more than you need.
Then, each time you treat you’ll be starting with a smaller and
smaller amount of cancer, because you’re not giving the cancer as
much time to grow between treatments,” explained Clifford Hudis,
M.D., another coauthor. “One of the exciting things about this study
is that it demonstrates we are able to shorten the time patients
have to be on chemotherapy, decrease the side effects, and at the
same time improve outcomes.”
“If confirmed with additional research, this approach may change
the standard of care in breast cancer treatment,” said Norton, who
added that the same concept might apply to other types of cancer.
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