Women with early breast cancer who receive higher-than-standard doses of two chemotherapy drugs (epirubicin and cyclophosphamide) as “add-on” therapy are at increased risk of subsequently developing cancer of the blood, a new study suggests.

Although add-on therapy with these drugs for early breast cancer has increased the number of long-term survivors, a small risk of secondary Acute myeloid leukemia (AML), with or without a pre-leukemia known as myelodysplastic syndrome (MDS), has been identified, they report in the Journal of Clinical Oncology.

Dr. David Rogers and his associates emphasize, however, that the therapeutic benefit of epirubicin and cyclophosphamide in early breast cancer has been “convincingly demonstrated.”

These regimens “have a strong benefit to risk ratio,” they explain, “and patients and clinicians can be reassured that the risk of Leukemia is likely to be low if the cumulative doses of these regimens are not exceeded.”

AML and MDS are conditions in which the bone marrow malfunctions and not enough red blood cells, white blood cells and platelets are present in the blood. These cells are the body’s natural defense system against diseases including cancer.

Rogers, with Gruppo Pfizer in Milan, Italy, and his team identified 30 women out of close to 9,800 who developed AML/MDS. All but one had been treated with epirubicin for early breast cancer.

According to the team, women taking higher than standard doses of epirubicin had a greater than 6-fold higher risk of developing AML/MDS compared with those taking standard doses of the drug. Women treated with epirubicin doses no higher than the standard had a low risk of developing leukemia.

Epirubicin and cyclophosphamide were usually administered in combination, the authors point out. For women who received higher than standard doses of both agents, the 8-year cumulative probability of developing AML/MDS was close to 5 percent - significantly higher than those taking standard doses of these agents.

The authors conclude that the increased risk of secondary leukemia “must be considered when assessing the potential benefit to risk ratio of higher than standard doses.”

SOURCE: Journal of Clinical Oncology June 20, 2005.