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Taking One Chemotherapy After Another May Lengthen Survival

8-year trial results show treatment with doxorubicin followed by docetaxel is superior to the two given at once

February 4, 2014

Written By Nicole Katze, MA, Editor and Manager, Publications
Reviewed By Heather L. McArthur, MD, MPH

Among women with early-stage breast cancer that travels to one or more lymph nodes in the underarm, treatment with the chemotherapy medicines doxorubicin (Adriamycin) followed by docetaxel (Taxotere) may lengthen survival more than giving the two at once. This finding comes from long-term results of the Breast International Group (BIG) trial 02-98.

Survival benefits in the study’s secondary analyses were seen in longer disease-free survival (DFS), the time from the start of treatment until the cancer grew or spread. They were also seen in overall survival (OS), the time from the start of treatment until death from any cause. 

Background

When BIG trial 02-98 opened in 1998, doctors knew chemotherapy given after surgery reduced the risk of breast cancer returning. Past trial findings made it clear that taxane-based chemotherapy, including docetaxel and paclitaxel, and anthracycline-based chemotherapy such as doxorubicin were very effective as first-line therapy for metastatic breast cancer. The role of these medicines in treating early-stage disease was not yet clear.

To fill this gap, the BIG trial team explored whether adding docetaxel to doxorubicin-based chemotherapy helped women with early-stage cancer that was also in the lymph nodes live longer without the disease coming back. They also assessed whether following doxorubicin with docetaxel, instead of giving the two medicines at one time, offered greater survival benefits.

Five-year follow-up data available in 2006 suggested that adding docetaxel to doxorubicin-based treatment might be more likely to improve DFS than doxorubicin-based treatment alone. The trial team also found that giving one medicine followed by the next, instead of the two combined, might lead to slightly longer periods of OS. Yet, more follow-up was needed to find out whether these trends would mean improved breast cancer-specific outcomes and, ultimately, survival.

After 8 years of follow-up, further data on DFS and OS are now available to help us know which way of giving these chemotherapies is best.

Design

A total of 2,887 women with early-stage breast cancer that traveled to at least one lymph node enrolled in the trial between June 1998 and 2001. They were treated in 173 cancer centers located in 21 countries and were between 18 and 70 years old.

The women were randomly assigned to one of four treatment groups. Each received doxorubicin (Adriamycin, A) followed by standard CMF chemotherapy for three cycles. In two of the four arms of the study, docetaxel was given either concurrently, together with an anthracycline, or sequentially, one after the other. The four courses of therapy given were:

  • Arm A (no taxane sequential arm): A at 75mg/m² once every 3 weeks for four cycles followed by CMF for three cycles
  • Arm B (no taxane concurrent arm): A at 60mg/m² with cyclophosphamide at 600mg/m² (AC) once every 3 weeks for four cycles followed by CMF for three cycles
  • Arm C (sequential arm with taxane): A at 75mg/m² once every 3 weeks for three cycles followed by docetaxel (T) at 100mg/m² once every 3 weeks for three cycles and then by CMF for three cycles
  • Arm D (concurrent arm with taxane) AT (50/75mg/m², respectively) every 3 weeks for four cycles then CMF for four cycles

Results

At 8 years of follow-up, the trial team found:

  • Adding docetaxel to doxorubicin-based chemotherapy did not improve DFS.
  • The group receiving the AT regimen (doxorubicin, followed by docetaxel, followed by CMF) experienced significant benefits in DFS and OS, seen as a 4.6 and 4.0 percent improvement, respectively, when compared with the  group receiving the AT regimen (doxorubicin plus docetaxel, followed by CMF).  These benefits must be viewed with caution given the limitations of the study.

Limitations

At 8 years of follow-up, DFS and OS benefits were seen from receiving doxorubicin followed by docetaxel. Yet, it is important to know that in the primary analysis there was no significant difference in DFS for those receiving the chemotherapies in this way. The primary analysis is the one the study was mainly designed to assess. In addition, there were differences across study arms in the dosing of the medicines and length of the treatment, making the results hard to interpret. More study is needed.

What This Means for You

If you and your doctor are planning your course of treatment for early-stage, node-positive breast cancer, it is OK to share these results and discuss the pros and cons of the order of chemotherapy medicines given. Ask your doctor to explain what he or she suggests and how it will help you most.

This study showed in a secondary analysis that women treated with doxorubicin, followed by a course of docetaxel, experienced longer DFS and OS than did women who received the two therapies at one time. You and your doctor may wish to consider these findings when planning your treatment. Yet, know each woman’s course of therapy will be unique to her needs.

To learn more about treatment options, see LBBC’s Guide to Understanding Treatment Decisions.

Oakman, C, Francis, P, Crown, J, et al. Overall survival benefit for sequential doxorubicin-docetaxel compared with concurrent doxorubicin and docetaxel in node-positive breast cancer – 8-year results of the Breast International Group 02-98 phase III trial. 2013; (24) 10: 1203 –1211.

Denver, CO  ·  September 13, 2014

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