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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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