Reducing the interval between chemotherapy treatment cycles or administering chemotherapy medications sequentially at higher doses, rather than simultaneously at lower doses, increases treatment efficacy and decreases the risk of breast cancer recurrence and death, a study suggests.
The study, “Increasing the dose intensity of chemotherapy by more frequent administration or sequential scheduling: a patient-level meta-analysis of 37 298 women with early breast cancer in 26 randomised trials,” was published in The Lancet.
Previous studies have shown that conventional chemotherapy medications, such as anthracyclines (e.g., doxorubicin) and taxanes (e.g., paclitaxel and docetaxel), reduce breast cancer mortality by one-third in women at the earlier stages of disease. However, “the optimal dosage and timing of these two drugs is still unclear,” according to the study.
Additionally, previous modeling studies proposed that increasing chemotherapy dose intensity might enhance the elimination of cancer cells, reduce the odds of cancer recurrence, and maximize the chances of a cure.
In theory, there are two different ways to boost chemotherapy dose intensity: The first is to shorten the interval between treatment sessions; and the second is to administer chemotherapies one at a time (sequential chemotherapy) at higher doses, instead of all at the same time at lower doses (standard concurrent chemotherapy).
To test if this increase in chemotherapy dose intensity could improve patients’ clinical outcomes, the Early Breast Cancer Trialists’ Collaborative Group (EBCTCG; a group of researchers from the MRC Population Health Research Unit and the University of Oxford) reviewed data from 26 randomized clinical trials comparing the efficacy of dose-intense therapy with a standard regimen.
Researchers analyzed data from 37,298 women with early-stage (operable) breast cancer from around the world who were treated between 1985 and 2011.
Results showed that women receiving chemotherapy every two weeks were 17% less likely to relapse and 15% less likely to die from breast cancer within the next decade than those receiving chemotherapy every three weeks.
Similar findings were obtained for patients treated with sequential chemotherapy compared with a concurrent regimen. Overall, there was a 14% reduction in the risk of breast cancer recurrence and a 4.3% reduction of cancer resurgence over 10 years.
Results were identical for women with estrogen receptor (ER)-positive and ER-negative tumors.
“The number of deaths from breast cancer in the United Kingdom and many other countries has halved over the last 30 years because of a series of step-by-step improvements in treatment that, together, add up to make a big difference,” Richard Gray, a professor of medical statistics in the Nuffield Department of Population Health at the University of Oxford, said in a press release.
“Previous work by the EBCTCG has shown that standard chemotherapy schedules reduce the risk of death from early-stage breast cancer by about a third. Though the benefits of dose-intense over standard chemotherapy are only moderate, this new research does show that by using dose-intense chemotherapy, the risk of dying of breast cancer can be reduced by at least 40% compared to no chemotherapy,” he said.
Physicians may be concerned about side effects related to dose-intense chemotherapy, but according to Jeremy Braybrooke, PhD, one of the study’s co-authors, the present study showed few additional side effects over standard chemotherapy.
“Some centres prefer giving chemotherapy every three weeks and don’t usually offer treatment every two weeks because of concerns about side effects and uncertainty about the additional benefit,” he said. “Looking at the data from large numbers of women receiving dose-intense chemotherapy, we have found no evidence to justify these concerns, and the results show definite benefit from the more intense treatments, including the fact that treatment can be completed sooner.”
Therefore, according to the study, “if chemotherapy is to be given, a dose-intense regimen should at least be considered.”