Dose Intense Chemotherapy Improves Survival in Early Stage Breast Cancer

Multiple studies and long term follow-up data confirm benefit of dose dense therapy in early stage breast cancer

Dose Intense Chemotherapy Improves Survival in Early Stage Breast Cancer

Giving chemotherapy drugs every two weeks instead of every three weeks reduces the risk of breast cancer recurrence and death in women undergoing adjuvant chemotherapy for early stage breast cancer. The analyses was performed by British physicians from the Early Breast Cancer Trialists Collaborative Group and published in the Lancet medical journal in April 2019. The doctors evaluated the outcomes of 37,000 women who participated in 26 clinical trials evaluating dose dense and standard dose chemotherapy.

In the United States (US) “dose intensive” chemotherapy is considered standard of care for the treatment of women with early stages of breast cancer. Adoption of this approach has lagged in the rest of the world and in some areas of the US.

The current analysis was designed to further determine if 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 is 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.

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 allows higher doses of the drugs to be used in each cycle while keeping the side effects manageable.

The researchers confirmed what several trials have already demonstrated; 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.

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 estrogen receptor (ER) positive and in ER-negative disease and did not differ significantly by any other characteristics.

Previous research demonstrated that standard chemotherapy schedules reduce the risk of death from early-stage breast cancer by about a third. The analyses confirmed once again the value of dose-intense chemotherapy and highlights that the overall risk of dying of breast cancer can be reduced by at least 40% when compared to no chemotherapy.

It is well known that some doctors administer chemotherapy every three weeks instead of every two weeks because of their concerns about side effects and “perceived” uncertainty about additional benefit form dose intensive therapy. The results of this study further demonstrate the inferiority of every 3 week chemotherapy.(1)

According to results presented at the 2006 San Antonio Breast Cancer Symposium (SABCS), updated results continue to demonstrate better efficacy with dose-dense chemotherapy than with conventional chemotherapy in early breast cancer.

Dose-dense chemotherapy (chemotherapy with a shortened interval between doses), has demonstrated improvement in outcomes compared to conventional chemotherapy in patients with high-risk, early breast cancer. Due to concerns about side effects, however, studies continue to evaluate the long-term effects of dose-dense therapy.

To compare dose-dense chemotherapy to conventional chemotherapy in patients with high-risk early breast cancer, researchers in Germany conducted a Phase III clinical trial.

The study enrolled 1,284 patients under the age of 65 who had at least four involved axillary (underarm) lymph nodes. Patients were assigned to receive either dose-dense or conventional chemotherapy with epirubicin, cyclophosphamide, and paclitaxel.

The results presented at the SABCS were from the third interim analysis.

  • There were no treatment-related deaths during therapy.
  • At five years relapse-free survival was 70% in the dose-dense arm, compared with 62% in the conventional-dose arm.
  • At five years overall survival was 82% in the dose-dense arm and 77% in the conventional-dose arm.
  • Quality of life declined during dose-dense therapy, but was recovered three months following completion of therapy.
  • 7% of patients in the dose-dense arm were hospitalized for febrile neutropenia (a low white blood cell count accompanied by fever), compared with just 2% in the conventional-dose arm.
  • There were no severe adverse effects on the heart and no unusual toxicities noted.

The researchers concluded that longer follow-up continues to demonstrate a significant improvement in relapse-free survival for dose-dense chemotherapy compared to conventional-dose chemotherapy in high-risk early breast cancer patients.

References:

  1. Moebus V, Leuck H, Thomssen C, et al. Dose-dense sequential chemotherapy with epirubicin, paclitaxel and cyclophosphamide in comparison to conventional dosed chemotherapy in high-risk breast cancer patients ³4+LN), mature results of an AGO-trial. Proceedings from the 2006 San Antonio Breast Cancer Symposium. Oral presentation December 17 2006. Abstract# 53.

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