Chemotherapy with doxorubicin plus cyclophosphamide followed by docetaxel improved overall time lived after breast cancer compared to two other combinations, results of a recent study indicate.

The results of this study were presented at the 31st Annual San Antonio Breast Cancer Symposium in December 2008. The data came from the National Surgical Adjuvant Breast and Bowel Project, trial B-30, a Phase III study involving more than 5,000 women.

The researchers compared schedules and combinations for the chemotherapies doxorubicin (brand name: Adriamycin), cyclophosphamide (brand name: Cytoxan) and docetaxel (brand name: Taxotere). They did not compare these medicines against other common chemotherapy treatments.

Study Background

In some early-stage breast cancers, cancer cells have the ability to travel away from the breast. One of the first places that cancer cells may travel is to the lymph nodes under the arm. The presence of cancer in the lymph nodes raises the possibility that other cells may have escaped and that a few microscopic cancer cells could have traveled throughout the body. To kill those cells, an oncologist may recommend chemotherapy to get any additional cancer missed by surgery.

In this study, researchers compared several chemotherapy medicines commonly given after surgery (called adjuvant therapy).

Cyclophosphamide, which belongs to a class of medications known as the alkylators, damages the proteins that control growth in the genes of the tumor cell. Docetaxel is a taxane, a medicine that works by slowing and stopping cell growth and division. Doxorubicin, an anthracycline, works by killing cancer cells.

The purpose of this study was to compare different schedules and combinations of these three medicines and determine what combination benefits women to the greatest extent.

Study Design

A total of 5,351 women participated in the study. The women all had breast cancers that could be removed with surgery and that had traveled to their lymph nodes. All participants with hormone receptor-positive breast cancers received the hormonal therapy tamoxifen after the completion of chemotherapy. Some of the women had radiation therapy after chemotherapy.

The women were divided randomly into three groups:

• Group one received four treatments with doxorubicin plus cyclophosphamide every three weeks, followed by four treatments with docetaxel also given every three weeks (receiving eight cycles of chemotherapy).
• Group two received four treatments with doxorubicin plus docetaxel every three weeks.
• Group three received four treatments with docetaxel, doxorubicin and cyclophosphamide together every three weeks.

The researchers followed the women for an average of 73 months after treatment. They evaluated overall survival, or overall time lived after treatment and disease-free survival, or time lived after treatment without evidence of breast cancer.

Study Results

The researchers found that the group one combination of doxorubicin plus cyclophosphamide followed by docetaxel decreased mortality by 17 percent compared to the group two combination of doxorubicin plus docetaxel without cyclophosphamide. This significant finding suggests the group one combination is the more effective treatment of the two.

The group one combination decreased mortality by 14 percent compared to the group three combination of docetaxel, doxorubicin and cyclophosphamide. The difference between groups one and three was small and not considered statistically significant. The treatments given to groups two and three were equally effective at improving overall survival, but the group one combination was superior to the other two regimens.

Women in group one were 17 percent less likely to have a recurrence compared to women in group three. They were 20 percent less likely to have a recurrence than women in group two.

Women experienced vomiting, mouth sores, low white blood cell counts, increased risk of infection and diarrhea. Several of these side effects were most severe in group one.

The researchers also found that some premenopausal women stopped having periods during chemotherapy. Those who stopped having periods for six months or longer had increased overall survival and increased disease-free survival.

Limits of the Study

This study has limitations because of its structure. The group one regimen may have been more effective because it was given for eight cycles instead of four cycles, as it was in the other two groups. Also, women in group one received docetaxel at a higher dose than the women in the other two groups. The difference in timing and dosage may explain why women in group one had more severe side effects than those in the other two groups.

Also, this study does not help researchers to determine how the group one regimen would fare if compared directly to other commonly used chemotherapy regimens. These include doxorubicin plus cyclophosphamide followed by paclitaxol (brand name: Taxol), often called AC/T, or docetaxel, doxorubicin and cyclophosphomide given for six cycles, often called TAC.

What Does This Study Mean for Me?

These findings show that four treatments with doxorubicin plus cyclophosphamide every three weeks, followed by four treatments with docetaxel also given every three weeks is an effective treatment for operable, node-positive breast cancer. It provides you and your healthcare team with another good option to consider, along with the standard chemotherapy regimens of AC/T and TAC.

Like all clinical trials, this study highlights the importance of research in advancing the treatment of breast cancer and the need to find more effective and less toxic combinations. If you are receiving chemotherapy, you can help by talking with your doctor about open studies. For example, open trials are looking at the use of novel chemotherapy treatment combinations and at adding the targeted therapy bevacizumab (brand name: Avastin) to standard chemotherapy. .

If you are a young woman, these findings suggest that by causing your ovaries to stop working, chemotherapy may further decrease your risk of recurrence.. If you want to have children, talk about your family-planning options with your doctor before you begin treatment. Your options may include choosing an alternative treatment or using fertility interventions such as preserving your eggs for after treatment.

For more information on fertility, listen to a podcast from our 2008 fall conference workshop session, Fertility and Pregnancy: Medical Update.

Read more about the study comparing chemotherapies for early breast cancer.