Increasing the dose intensity of chemotherapy reduces the risk of breast cancer recurrence and death
11 February 2019
Giving chemotherapy drugs every 2 weeks instead of the usual every 3 weeks reduces the risk of breast cancer recurrence and death, according to research published in The Lancet on 7 February 2019.
The study, undertaken by the Early Breast Cancer Trialists’ Collaborative Group (EBCTCG), analysed data from over 37,000 women with early (operable) breast cancer who had taken part in 26 randomised trials from across the world that compared dose-intense chemotherapy with standard schedule chemotherapy.
The analysis aimed to find out whether increasing the dose intensity of chemotherapy (the amount of drug delivered per unit time), was more effective at lowering breast cancer recurrence and death rates than standard schedule chemotherapy regimens. One way to increase dose intensity was to use the same chemotherapy agents at the same doses but administer treatment every two weeks instead of every three weeks. ‘The average weekly dose is therefore 50% higher with 2-weekly treatment than with the standard 3-weekly schedule comparator,’ explained Professor Richard Gray, Professor of Medical Statistics in the Nuffield Department of Population Health at the University of Oxford, and one of the study authors.
Another way of increasing the dose intensity of chemotherapy was to give the drugs individually in sequence rather than administering all the drugs together at the same time. This allowed higher doses of the drugs to be used in each cycle while keeping the side effects manageable.
‘We were surprised by how strong and consistent the findings from our study were,’ Gray said. ‘Patients who received chemotherapy every two weeks were 17% less likely to have disease recurrence and 15% less likely to die from breast cancer within 10 years, compared with those who received treatment every three weeks. Similar results were seen for patients who received sequential chemotherapy rather than concurrent treatment and, overall, analysing all the patients together there was a 14% proportional reduction in the risk of breast cancer recurrence. The reduction in the 10-year risk of breast cancer recurrence was 4.3%.’
The results apply to most women who are recommended chemotherapy for early-stage breast cancer. The reduction in recurrence with dose-intense chemotherapy across all trials was similar in oestrogen receptor (ER) positive and in ER-negative disease, and did not differ significantly by any other patient or tumor characteristics.
‘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. 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,’ said Gray.
There were few additional side-effects with the dose-intense schedule compared with standard schedule chemotherapy. ‘Some centres prefer giving chemotherapy every 3 weeks and don’t usually offer treatment every 2 weeks 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 definite benefit from the more intense treatments, including the fact that treatment can be completed sooner,’ said Dr Jeremy Braybrooke, another of the study authors, and Senior Clinical Research Fellow in the Nuffield Department of Population Health, University of Oxford.
‘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, more research is still needed as it is difficult to recommend any one particular dose-intense chemotherapy regimen based on this study,’ said Braybrooke.
The research was funded by Cancer Research UK and the UK Medical Research Council.
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Notes for editor:
Richard Gray, Professor of Medical Statistics in the Nuffield Department of Population Health at the University of Oxford, United Kingdom
Jeremy Braybrooke Consultant Medical Oncologist at University Hospitals Bristol NHS Foundation Trust and Senior Clinical Research Fellow, Nuffield Department of Population Health at the University of Oxford, United Kingdom.
The authors declare no conflicts of interest.
Nuffield Department of Population Health The (NDPH) is a world-leading research institute, based at the University of Oxford, that investigates the causes and prevention of disease. NDPH has over 500 staff working in a number of world-renowned population health research groups, including the Clinical Trial Service Unit and Epidemiological Studies Unit (CTSU), the Cancer Epidemiology Unit (CEU), the National Perinatal Epidemiology Unit (NPEU) the World Health Organization Collaborating Centre on Population Approaches for Non-Communicable Disease Prevention (CPNP) and other groups working on public health, health economics, ethics and health record linkage. It is also a key partner in the new Oxford University Big Data Institute. For further information, please visit ndph.ox.ac.uk.
The Early Breast Cancer Trialists’ Collaborative Group
The Early Breast Cancer Trialists’ Collaborative Group (EBCTG) was established in 1985 to bring together all the evidence on major questions relating to long-term benefits and side-effects of different breast cancer treatment options. Several hundred research groups have shared individual patient data on more than 600,000 women in 500 randomised trials for the EBCTCG meta-analyses that have produced definitive estimates of the effects of various treatments on time to recurrence, breast cancer death, second cancers and death from other causes. The large EBCTCG datasets also allow the most reliable possible exploration of any differences in the effects of the treatments in particular subgroups of women, or between treatments within the same class. The group’s findings are widely used in consensus statements, clinical guidelines, decision aids, and treatment decisions around the world. They have influenced the care of millions of women over the last four decades, making a major contribution to the large falls in worldwide breast cancer mortality seen over this period. For further information, please visit ctsu.ox.ac.uk/research/ebctcg.
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