A study conducted by the Cancer and Leukemia Group B (CALGB) and presented at the 25th Annual San Antonio Breast Cancer Symposium assessed the effectiveness of reducing the interval between successive doses of a commonly used chemotherapy regimen to improve survival rates in breast cancer women. This study was conducted as follow-up of a mathematical model which was developed in the 1980s that suggested the value of increased dose density.
Researchers tested both dose dense and conventional chemotherapy regimens in 1,973 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):
Sequential administration (A followed by T, followed by C) in three-week intervals (conventional)
Sequential administration in two-week intervals, with filgrastim (dose dense)
Concurrent administration (A and C together, followed by T) in three-week intervals
Concurrent administration in two-week intervals, with filgrastim (dose dense)
The dose dense regimen was made tolerable to patients with the drug filgrastim, which helps prevent neutropenia, a serious complication of chemotherapy. In neutropenia there is a decline in the number of a certain type of white blood cells which hampers the immune system of the body. Filgrastim, also known as the granulocyte-colony stimulating factor (G-CSF), helps prevent neutropenia by stimulating the formation of white blood cells called neutrophils. Without it, chemotherapy dosing frequency is limited to longer intervals.
The researchers found that the disease-free survival was 82 per cent 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. They also found that the efficacy did not differ between the two dose regimens.
The study also indicated that dose dense chemotherapy could lead to higher overall survival rates. After three years, 92 percent of patients on the dose dense therapy were alive, compared to 90 percent of those on the conventionally administered regimens. This difference corresponded to a 31 percent overall reduction in the risk of death. However, the study authors cautioned that additional follow-up is necessary to confirm this overall survival benefit.
The study also found that patients on dose dense chemotherapy did not have increased side effects than those on the conventional treatments. It was also found that sequential administration produced slightly fewer side effects than the concurrent regimens, with equal efficacy.
Larry Norton, M.D., of Memorial Sloan-Kettering Cancer Center, Senior investigator of the study believed that this study which showed an improvement due to dose dense chemotherapy could advance knowledge of the biology of breast cancer and how best to treat it. He also added that further confirmed studies would affect the care of thousands of patients throughout the world with breast cancer and perhaps, eventually, other diseases.
Researchers also hypothesize that future clinical trials could examine the benefits of dose dense chemotherapy using other drugs and in other types of cancer as the mathematical model on which the study was based applied to most cancer types and many anti-cancer drugs.