LEXINGTON, KY (June 15, 1998) -- Researchers at the University of Kentucky Markey Cancer Center recently announced the beginning of a novel clinical trial designed to improve the outcome of metastatic breast cancer in some women. The most frequently diagnosed non-skin cancer among women in the United States, breast cancer was expected to kill more than 40,000 women in 1997.
Decades of research with traditional anti-cancer therapies, such as conventional chemotherapy and hormone manipulation, have improved outcomes only marginally, although many women do live longer as a result.
"Women with advanced breast cancer benefit from transplants, but are rarely cured," said Kenneth Foon, M.D., chief of hematology/oncology and director of the UK Markey Cancer Center. "It is our hope that by adding a vaccine therapy to stimulate an immune response, we will destroy residual tumor cells that remained following chemotherapy."
Foon and Donna Reece, M.D., a hematologist/oncologist and director of the Blood and Marrow Transplant Outpatient Clinic, have combined two treatment methods into a single treatment program to improve survival rates.
The first requires high-dose chemotherapy to kill the cancer cells. The second involves the administration of a vaccine to enhance the body's immunity against cancer cells.
High-dose chemotherapy and autologous stem cell rescue are the first treatment steps. Autologous stem cell rescue involves the use of the patient's own blood to obtain stem cells, the precursors of all blood cells. Stem cells will regenerate bone marrow function in the patient after high-dose chemotherapy.
Because high-dose chemotherapy will destroy the patient's bone marrow, stem cells are collected after a small dose of chemotherapy and growth factors. The purified cells are frozen in liquid nitrogen for later use.
Metastatic breast cancer recurs in up to 90 percent of cases after high-dose therapy. To combat the recurrence of disease, a vaccine, called an anti-idiotypic monoclonal antibody, is administered as the second component of the new treatment. Developed by Foon and colleague Malaya Chatterjee, Ph.D., professor of internal medicine, UK College of Medicine, the vaccine mimics a protein found on tumor cell surfaces in order to stimulate an immune response in the body.
The patient's body is unable to recognize tumor cells as foreign, and therefore does not generate an immune response against the cancer. The vaccine lets the body recognize cancer cells as foreign and to mount an immune response against them. Accordingly, use of the vaccine after a transplant - when the volume of residual tumor cells is relatively low - may be the ideal situation.
However, an inevitable period of severe suppression in the patient's immune system is seen following a stem cell transplant. Until the immune system fully recovers, the vaccine likely would not stimulate the patient's re-emerging immune defense mechanisms against the cancer. In light of this fact, the patient's immune system is stimulated by the vaccine before stem cell collection. Cells that "remember" immunity are, therefore, collected with the stem cells. The patient receives these with the stem cell transplant after high-dose chemotherapy.
Supplemental vaccinations begin again about one week after the transplant and will continue once a month for up to two years.
The treatment plan:
- Vaccine administered to stimulate immune cells
- Chemotherapy and growth factors stimulate stem cell growth
- Stem cells are collected
- High-dose chemotherapy
- Stem cell transplant
- Vaccine readministered one week after transplant
- Vaccine continues once a month for up to two years
Criteria for women to participate in the study:
- No more than 70 years old
- Have proven metastatic breast cancer
- Breast cancer must not involve the brain or bone marrow
- Must have responded to conventional chemotherapy given after diagnosis of metastases
- Are otherwise fit