SABCS 2017: Increasing the Dose Intensity of Chemotherapy May Lower the Risk of Breast Cancer Recurrence and Death
Increasing the dose intensity of chemotherapy—by either shortening the intervals between the cycles or by sequential administration instead of concurrent administration of the drugs—reduced the risk of early-stage breast cancer recurrence and death compared with standard chemotherapy regimens, according to data from an Early Breast Cancer Trialists' Collaborative Group (EBCTCG) meta-analysis study presented by Gray et al at the 2017 San Antonio Breast Cancer Symposium (Abstract GS1-01).
“The number of deaths from breast cancer in the United States and many other countries has halved over the past 30 years because of a series of step-by-step improvements in treatment that, together, add up to make a big difference,” said Richard Gray, MSc, Professor of Medical Statistics in the Nuffield Department of Population Health at University of Oxford. “It is important to continue to find out whether or not there are worthwhile benefits from one treatment compared to another.”
Meta-analysis Details
Dr. Gray and colleagues aimed to find out whether increasing the dose intensity of chemotherapy was more effective at lowering breast cancer recurrence and death rates than standard chemotherapy regimens for patients with early-stage breast cancer. The dose-dense chemotherapy trials used the same chemotherapy agents at the same doses—but administered every 2 weeks instead of every 3 weeks. The average weekly dose is therefore 1.5 times higher in the dose-dense group than with the standard schedule comparator, Dr. Gray explained.
“Another way of increasing the dose intensity of chemotherapy is to give the chemotherapeutics individually in sequence rather than administering all the drugs together at the same time,” said Dr. Gray. This sequential approach allows higher doses of the individual drugs to be used in each cycle while keeping the side effects manageable, he added.
For the meta-analysis, Dr. Gray and team used individual patient data from 7 randomized trials (10,004 women) that tested chemotherapy given every 2 weeks vs every 3 weeks, and from 9 randomized trials (11,533 women) that tested sequential vs concurrent anthracycline and taxane-based chemotherapies.
Major Findings
“We were surprised by how strong and consistent the findings from our study were,” Dr. Gray said.
Patients who received chemotherapy every 2 weeks were 17% and 15% less likely to have disease recurrence and die from breast cancer within 10 years, respectively, compared with those who received treatment every 3 weeks. Similarly, patients who received sequential chemotherapy were 14% and 13% less likely to have disease recurrence and die from breast cancer within 10 years, respectively, compared with those who received concurrent treatment.
“The results apply to most women receiving chemotherapy for early-stage breast cancer: The 15% reduction in recurrence with dose-intense chemotherapy across all trials was similar in estrogen receptor (ER)-positive and in ER-negative disease, and did not differ significantly by any other patient or tumor characteristics, including age, HER2 status, nodal status, tumor size, and grade,” noted Dr. Gray.
There were few additional side effects with the dose-intense schedule compared with standard schedule chemotherapy, and fewer patients who received dose-intense treatment died from non–breast cancer causes than those who received standard treatment.
“Some centers prefer giving chemotherapy every 3 weeks and offer treatment every 2 weeks less frequently because of concerns about side effects and uncertainty about the additional benefit. 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 consistent benefit from the more intense treatments,” Dr. Gray said.
A limitation of the study is that the chemotherapy used in the dose-intensification trials varied in the doses, the number of treatment cycles, and the agents used. So, although dose-intense chemotherapy is clearly more effective at eradicating cancers, it is difficult to recommend any one particular dose-intense chemotherapy regimen based on this study, said Dr. Gray.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
