High-Dose Chemotherapy for Advanced Breast Cancer: New Study Shows No Improvement in Outcomes for Persons who Responded to Initial Standard-Dose Chemotherapy


High-Dose Chemotherapy for Advanced Breast Cancer: New Study Shows No Improvement in Outcomes for Persons who Responded to Initial Standard-Dose Chemotherapy

Women with metastatic breast cancer—breast cancer that has spread beyond the breast and lymph nodes under the arm—often receive a combination of chemotherapy drugs to relieve the symptoms of the disease and to prolong survival time. A controversy has arisen among researchers as to whether the use of higher than standard doses of chemotherapy, followed by a stem cell transplantation (SCT), is of any added benefit. A large group of researchers now say that a recently studied high-dose chemotherapy regimen showed no benefit over standard-dose therapy for women with metastatic disease who responded to initial standard-dose chemotherapy.

Treatment for cancer of the breast, a common cancer in women, is dependent on many factors. One of the main considerations in making a treatment choice is the stage of cancer, or the extent of disease at the time of diagnosis. In the case of

advanced or

metastatic breast cancer, treatment options may include chemotherapy combinations, radiation therapy, hormone therapy, biologic therapy (to help the immune system fight the cancer), and/or sometimes surgery. In addition, some studies have shown that the use of high-dose chemotherapy with an SCT to be beneficial. High-dose chemotherapy can kill more cancer cells than standard chemotherapy; however, it also causes more damage to the blood cells, particularly those in the bone marrow. The bone marrow (and circulating blood) contains early blood-forming cells, called

stem cells, which grow and mature into the 3 blood cell types: white blood cells (protect the body from infection), red blood cells (carry oxygen to the tissues), and platelets (help the blood to clot). A

stem cell transplantation is a procedure that allows the stem cells that are destroyed by high-dose chemotherapy to be replaced with healthy stem cells. In the case of an

autologous SCT, stem cells are collected from the blood or bone marrow of the patient before the high-dose chemotherapy is given. The cells are frozen and stored and are then infused back into the patient after he or she has undergone the high-dose chemotherapy to kill the cancer cells. This procedure replaces the stem cells that have been destroyed by the high-dose chemotherapy, thereby allowing more rapid recovery and production of the red blood cells, white blood cells, and platelets that the body needs. Researchers have been studying this treatment strategy in an effort to provide women with metastatic breast cancer with greater relief of symptoms and prolonged survival times.

Researchers from several medical centers treated 553 women, ages 18 to 60 years, with 4 to 6 cycles of a standard-dose chemotherapy combination. Then, those who had a complete or a partial response to this therapy were assigned to receive additional therapy with either: A) up to 24 cycles of standard-dose chemotherapy with cyclophosphamide, methotrexate, and fluorouracil or B) a single course of high-dose chemotherapy with carboplatin, thiotepa, and cyclophosphamide. Results showed that, of the 553 women treated, 10.5% had a complete response and 46% had a partial response to the initial standard-dose chemotherapy. One hundred ten persons were then assigned to receive the additional high-dose regimen with SCT, 89 persons the additional standard-dose regimen. The 3-year survival rates were 38% for those receiving the standard chemotherapy, and 32% for those receiving the high-dose chemotherapy. Twelve percent of those in the standard-dose group had no progression of disease, compared with only 6% in the high-dose group. Furthermore, there were more side effects in the high-dose therapy group, including 1 treatment-related death.

This study indicates that there were no differences in survival between the standard-dose and high-dose chemotherapy regimens in women with metastatic breast cancer who had a complete or partial response to initial standard-dose therapy. However, the number of women treated in this trial does not allow the identification of any subsets of women that might benefit more than the overall group from the high-dose regimen.

Although these findings clearly suggest that the use of this high-dose chemotherapy regimen with SCT produced greater side effects with no added benefit over the standard-dose chemotherapy, other clinical trials to evaluate similar high-dose chemotherapy combinations are still underway. Some clinical trials are also investigating the use of the drug, Herceptin®, before and/or after receiving a high-dose chemotherapy regimen with a SCT. Individuals who have metastatic breast cancer may wish to talk with their doctor about the standard therapies available, as well as the risks and benefits of different high-dose chemotherapy combinations compared with the risks and benefits of other new treatments that are being studied in clinical trials. Sources of information on ongoing clinical trials that can be discussed with a doctor include a comprehensive, easy-to-use service provided by the National Cancer Institute (

cancer.gov) and the Clinical Trials section and service offered by Cancer Consultants.com (

www.411cancer.com). (

New England Journal of Medicine, April)

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