A new clinical trial demonstrating that reducing the interval between successive doses of a commonly used chemotherapy regimen improves survival in women whose breast cancer has spread to the lymph nodes was presented at the 25th Annual San Antonio Breast Cancer Symposium in December. While previous research has evaluated the use of various forms of dose-dense chemotherapy, this is the first major controlled study to show a clear survival benefit for women with node-positive breast cancer. The first study was conducted by Cancer and Leukemia Group B (CALGB) for the Breast Cancer Intergroup, a consortium of National Cancer Institute (NCI)-sponsored Cooperative Clinical Trials Groups and enrolled 2,005 women with node positive breast cancer and randomized them to one of four regimens.
Marc L. Citron, M.D., Albert Einstein College of Medicine, who is the lead investigator of the study, has said, “This study suggests that many women with breast cancer may benefit from chemotherapy administered on a condensed schedule. With the availability of new drugs to control one of the most serious side effects of chemotherapy administration, we can further increase the chances of survival for women with breast cancer.” The newer dose dense regimen is made tolerable for patients by using the drug filgrastim (Neupogen), which helps prevent neutropenia, a serious complication of chemotherapy.
The researchers found that two dose dense regimens provided significantly higher disease-free survival rates than two regimens using conventional dosing, and that efficacy did not differ between the two dose dense regimens. Among patients on the dose dense regimens, disease-free survival was 82 percent after four years, compared to 75 percent for those who received conventional therapy. This difference corresponded to a 26 percent overall reduction in the risk of cancer recurrence. The findings confirm the predictions of a mathematical model developed in the 1980s that suggested the value of increased dose density, and which were the impetus for the study.
“The improvement in outcome could well represent an important advance in our knowledge of the biology of breast cancer and how best to treat it,” said Larry Norton, M.D., of Memorial Sloan-Kettering Cancer Center, senior investigator for the study and one of the developers of the original model. “If confirmed and extended by additional research, this finding could positively affect the care of thousands of patients throughout the world with breast cancer and perhaps, eventually, other diseases.”
The study tested both dose dense and conventional chemotherapy regimens in 2,005 women with node-positive primary breast cancer and no other metastases. Following surgical removal of their tumors, the women were assigned to one of four treatment regimens involving the standard chemotherapy drugs doxorubicin (A), paclitaxel (T), and cyclophosphamide (C):
Frequent administration of chemotherapy can result in
a decline in the number of a certain type of white blood cells, leading
to a condition called neutropenia. Researchers administered filgrastim
(Neupogen) also known as the granulocyte-colony stimulating factor (G-CSF),
to dose dense treatment
“It is too soon to determine whether a dose dense chemotherapy regimen with filgrastim should be the new standard of care,” said Jeffrey Abrams, the oncologist in charge of breast cancer treatment trials at NCI. “However, the reduced risk of cancer recurrence and the low occurrence of side effects are encouraging, and further follow-up as well as other studies testing this approach will hopefully confirm the findings.”
Side effects were found to be no more severe among patients
on the dose dense regimens than among those on the conventional treatments,
and patients on the dose dense regimens suffered fewer cases of neutropenia.
The study also showed that sequential administration produced slightly
fewer side effects than the concurrent regimens, with equal efficacy.
In addition to improved disease-free survival, the study indicated that
dose dense chemotherapy may also lead to higher overall survival rates.
Additional follow-up study is necessary to confirm a survival benefit.
The study will be published in the Journal of Clinical
Oncology. Citron, ML et al. Superiority of dose dense over conventional
scheduling and equivalence of sequential vs. combination adjuvant chemotherapy
for node-positive breast cancer (CALGB 9741, INT C9741).
Copyright © 2014 Bay Area Breast Cancer Network. All rights reserved.
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