Increasing Chemotherapy Dose Intensity May Lower Risk of Breast Cancer Mortality

A meta-analysis presented at the 2017 San Antonio Breast Cancer Symposium suggests that increasing the dose intensity of chemotherapy may reduce the risk of disease recurrence and death among patients with breast cancer.

The researchers found that shortening the length of time between treatments or opting for sequential administration may present significant benefits to patients with early-stage disease compared with standard chemotherapy.

“The number of deaths from breast cancer in the United States 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,” said researcher Richard Gray, MSc. “It is important to continue to find out whether or not there are worthwhile benefits from one treatment compared to another.”

The study authors aimed to determine whether increasing the amount of chemotherapy delivered at once was more effective at reducing disease recurrence and mortality rates compared with the standard approach.

In the analysis, the same chemotherapy at the same doses was administered every 2 weeks instead of every 3 weeks, meaning that the weekly dose was 1.5 times higher.

“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,” Gray said.

The authors noted that the sequential approach allows for higher doses of individual drugs while limiting side effects.

Included in the study were 10,004 women from 7 randomized trials that examined the effects of 2-week administration and another 11,544 women from 9 randomized trials that examined sequential anthracycline and taxane-based chemotherapies.

“We were surprised by how strong and consistent the findings from our study were,” Gray said.

The findings showed that patients who were administered chemotherapy every 2 weeks were 17% less likely to experience disease recurrence and 15% less likely to die from breast cancer within 10 years compared with patients treated every 3 weeks, according to the study.

The authors also found that patients who received sequential chemotherapy were 14% less likely to experience disease recurrence and 13% less likely to die from breast cancer within 10 years compared with patients 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 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,” Gray said.

However, the analysis showed that patients experienced additional side effects on a dose-intense schedule compared with the standard regimen. Also, fewer patients on dose-intense treatment died from non-breast cancer causes compared with those who received standard treatment, which may have skewed results, according to the study.

“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,” Gray concluded.