High-Dose Chemo With Stem Cell Transplant Does Not Improve Outcome for Breast Cancer

 

 

Behind the Cancer Headlines®

July 8, 2003

 

 

High-dose chemotherapy coupled with a stem cell transplant does not improve the outcomes of post-operative patients with advanced breast cancer, according to findings of a new multi-center study.

 

The research, published in the New England Journal of Medicine, should alter the treatment approach for patients with primary breast cancer that has spread to the regional lymph nodes, says study leader Hillard M. Lazarus, MD, Director of the Blood and Marrow Transplantation Program at University Hospitals of Cleveland.

 

"We found that an autologous stem cell transplant—high-dose chemotherapy followed by either bone marrow or blood from the patient herself—did not significantly increase the survival rate of women with early stage breast cancer that had spread to at least 10 lymph nodes in the axillary (arm pit) area," Lazarus says.

 

"These results have enhanced our understanding of the disease and motivate us to explore alternatives to stem cell transplantation. It is evident that high dose chemotherapy destroys more cancer cells, but its complications can also be deadly to patients. We need to look at what we've learned about high dose chemotherapy and transplantation through this study, and use it as a platform on which to build similarly strong, yet safer treatments."

 

Lazarus and his colleagues studied 511 primary breast cancer patients whose tumor had spread to at least 10 lymph nodes under the arm. Half of the group was treated with conventional chemotherapy-only for six months, and the other half received the identical chemotherapy followed by high-dose chemotherapy and a stem cell transplant. All patients received the conventional dose of three drugs: cyclophosphamide, doxorubicin and fluorouracil. The high-dose chemotherapy consisted of cyclophosphamide and thiotepa.

 

Although there were many fewer relapses in the patients assigned to receive an autograft, the overall results showed that there was no significant difference in survival rates between the two groups. However, nine of the 511 patients died of transplantation complications. Nine others developed myelodysplastic syndrome (a pre-leukemia condition) or acute myeloid leukemia.

 

The procedure combines the administration of high doses of chemotherapy with the transplantation of stem cells from the patient's own blood or bone marrow. High-dose chemotherapy kills healthy blood cells as well as cancer cells, so stem cells are transplanted to restore the patient's blood production. The infused stem cells regenerate white blood cells to fight infection, red blood cells to carry oxygen and platelets that enable blood to clot.

 

These stem cells, taken from the patient's body (autologous) or from another person (allogeneic), are infused through a vein and travel to bone marrow to produce new white blood cells, red blood cells and platelets, enhancing the patient's health.

 

This life-saving treatment has been used successfully for more than twenty-five years to cure various types of leukemias and lymphomas. More recently, the treatment has proven effective for patients with multiple myeloma (bone cancer) and certain non-malignant disorders.

 

In the last decade, this modality was used with promising results in women with breast cancer whose prognosis was poor. Only 20 to 30 percent of such women with high-risk breast cancer were cancer-free five years after surgery.

 

In the 1980s and 1990s, some researchers found high-dose chemotherapy and autologous transplantation to be a promising therapy for breast cancer patients at high risk for relapse.

 

In a separate study in the same issue of the New England Journal of Medicine, researchers at the Netherlands Cancer Institute concluded that there is a benefit to high dose chemotherapy and transplant, with a 10% greater relapse-free survival among women who received the high-dose approach versus conventional therapy. This benefit was most evident among women under 40 years old with HER2/neu negative tumors (breast cancers that exhibit less aggressive features).

 

It should be noted that the chemotherapy regimens used in both studies, designed and activated more than a decade ago, differ from current conventional and high-dose chemotherapy approaches used in many cancer centers today. Moreover, Lazarus remains concerned about the secondary cancers and complications associated with high-dose treatments analyzed in this study.

 

"Conventional-dose chemotherapy remains the standard of care for most breast cancer patients who are at high risk for relapse due to lymph node involvement," says Lazarus. "But blood stem cell or bone marrow transplantation remains a promising therapy and requires further study."

 

 

SOURCES:

 

New England Journal of Medicine, July 3, 2003

University Hospitals of Cleveland (http://www.uhhs.com)