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Chemotherapy Combination Less Toxic to Heart

April 8, 2010

Written By Mary Alice Hartsock
Reviewed By Edith A. Perez, MD

When used with trastuzumab after surgery, chemotherapies with and without anthracyclines worked similarly, but combinations without anthracyclines proved less harmful to the heart, a study of women with HER2 positive, early breast cancer indicates.

Researchers presented this updated analysis of the Phase III trial BCIRG 006 at the 2009 San Antonio Breast Cancer Symposium (Abstract 62). Women who took trastuzumab plus docetaxel and carboplatin (brand names: Herceptin, Taxotere and Paraplatin) received fairly similar benefit as those who took trastuzumab plus the anthracycline-containing medicine doxorubicin (brand name: Adriamycin). However, those who took doxorubicin had more side effects to the heart. There were no deaths related to heart problems among any study participants.

Study Background

Anthracyclines are a family of chemotherapy treatments used to stop the spread and growth of cancer cells. These standard treatments for early-stage disease have been proved in clinical trials to improve survival and to decrease the chances of breast cancer returning. Herceptin, a targeted therapy, blocks a receptor on the cancer cell that has too much HER2 protein.

Used individually or with other treatments, anthracyclines and trastuzumab may increase the risk for heart problems, depending on the dosage and how the medicines are given. When used together at the doses and frequency of the past—which tend to be higher than doctors use today—.these medicines have caused serious side effects, leaving researchers looking for other effective combinations.

Study Design

The researchers randomly assigned 3,222 women with HER2 expressing, lymph node positive or high-risk lymph node negative breast cancer to receive one of three treatments.

Group 1 received doxorubicin and cyclophosphamide followed by docetaxel (called ACT).

Group 2 received doxorubicin and cyclophosphamide followed by docetaxel with trastuzumab (called ACTH).

Group 3 received docetaxel plus carboplatin plus trastuzumab (called TCH).

Study Conclusions

After five-and-a-half years, the women who received anthracycline-containing treatments had roughly equivalent disease-free survival (time during the study without cancer returning) and overall survival (time lived during the study) to those who did not receive anthracycline-containing treatments:

  • Group 1, who received ACT, had 75 percent disease-free survival and 87 percent overall survival
  • Group 2, who took ACTH, had 84 percent disease-free survival and 92 percent overall survival
  • Group 3, who got TCH, had 81 percent disease-free survival and 91 percent overall survival

All women who took trastuzumab did better than those who did not; today, trastuzumab-containing treatments are the standard of care for HER2 positive disease. ACTH was slightly more effective at reducing recurrence than TCH: 83 participants in the ACTH arm died of breast cancer, versus 97 women in the TCH group.

The women whose treatment did not contain an anthracycline (TCH) had fewer acute and chronic heart problems than those taking ACTH. Also, women in the groups with anthracycline-containing chemotherapies developed congestive heart failure (trouble pumping blood through the heart) more often than those in the TCH group.

What This Study Means for You

These study results confirm that trastuzumab added to chemotherapy will reduce the risk of recurrence and improve chances of survival in early-stage, HER2 positive breast cancer. They suggest that another treatment combination, TCH, might be an option for you if you cannot take an anthracycline-based medicine for other reasons. Regardless of what chemotherapy you take, if you receive Herceptin, your doctor should monitor your heart health and address any problems you have along the way. For more information on making choices about medicine, please download a copy of our Guide to Understanding Treatment Decisions.

Phase III Randomized Trial Comparing Doxorubicin and Cyclophosphamide Followed by Docetaxel (AC→T) with Doxorubicin and Cyclophosphamide Followed by Docetaxel and Trastuzumab (AC→TH) with Docetaxel, Carboplatin and Trastuzumab (TCH) in HER2neu Positive Early Breast Cancer Patients: BCIRG 006 Study. San Antonio Breast Cancer Symposium, December 2009. Abstract 62.

Read more about this chemotherapy study.