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Also in the July 29 JNCI
Date:7/29/2008

The Same Dose of Anthracycline Is Not Safe for Everyone

Not all patients can tolerate the currently recommended cumulative dose of epirubicin. New models can help physicians calculate the epirubicin dose associated with a 5 percent risk of cardiotoxicity for individual patients.

Oncologists frequently use anthracyclines, including epirubicin and doxorubicin, to treat breast cancer patients. However, the drugs cause lasting heart problems in a substantial number of patients. To limit the problem, current treatment guidelines suggest that patients receive no more than 900 mg/m2 epirubicin over the course of their cancer care.

In the current study, Marianne Ryberg, M.D., of the University of Copenhagen and colleagues followed 1,097 patients with metastatic breast cancer who were treated in a single hospital near Copenhagen between 1983 and 2003. The researchers assessed patients' risk factors for cardiotoxicity and corrected for the risk of death from all other competing causes of death, including cancer. (The studies that have previously concluded that the upper safe limit of epirubicin is 900 mg/m2 have not generally corrected for other causes of death.) Using these data, they calculated the maximum cumulative dose of epirubicin that is associated with a 5 percent risk of developing heart disease.

Ryberg and colleagues found that patient age, predisposition to heart disease, previous chest irradiation, and prior hormonal cancer therapy were associated with an individual's risk of developing heart problems following epirubicin treatment. By contrast, the researchers found that treatment with less epirubicin, a higher tumor burden, prior chemotherapy, and older age of the patient were associated with an increased risk of death from other, non-cardiac, causes.

Based on these data, the researchers lowered the cumulative dose recommended for most patients, with maximum doses ranging from 300 mg/m2 to 900 mg/m2. "
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Contact: Liz Savage
elizabeth.savage@oxfordjournals.org
301-841-1287
Journal of the National Cancer Institute
Source:Eurekalert

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