Aug. 4, 2008 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, researchers report in the July 29 online issue of the Journal of the National Cancer Institute.
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. "Treatment with a potentially cardiotoxic drug may often be inevitable to extend survival for a cancer patient. However, it is essential to be aware of the risk of cardiotoxicity, not only because cardiotoxicity can progress to a potentially fatal out¬come if not treated but also because it lowers the quality of patient life," the authors write.
In an accompanying editorial, Dawn Hershman, M.D., and Alfred I. Neugut, M.D., Ph.D., of Columbia University Medical Center in New York write that it has been difficult to predict which patients are most likely to develop cardiotoxicity following anthracycline therapy. Neither randomized clinical trials nor studies that rely on large administrative databases are adequate for addressing the issue. Therefore, Ryberg's study is an important step to helping physicians personalize cancer care for their patients.
"If we can better predict who is at greatest risk for toxicity and who is not, we may be able to comfortably offer stan¬dard treatment to a larger percentage of the population," the editorialists write.
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