Epirubicin is effective against breast cancer with low cardiotoxicity almost a decade after completion of chemotherapy, according to an article in the August issue of the Journal of Clinical Oncology.

The current work is the first substudy to evaluate patients more than eight years after they completed adjuvant treatment with epirubicin; it builds upon results of the French Adjuvant Study Group (FASG-05) trial that demonstrated significant 5- and 10-year disease-free and overall survival benefits in patients treated with one of two different doses of epirubicin.

The current analysis is part of the emerging movement among healthcare professionals to analyze the long-term side effects associated with commonly used chemotherapy agents and new biologic and targeted therapies.

“Past research indicates that because of its safety profile, including its cardiac safety, epirubicin is emerging as a standard treatment for women with early-stage breast cancer,” said Aman Buzdar, MD. “The results of this study demonstrate that the significantly improved disease-free and overall survival associated with higher doses of epirubicin are not compromised by the potential for cardiotoxicity.”

In the substudy, which was funded by the drug manufacturer, investigators evaluated the long-term effects of two different doses of epirubicin on cardiotoxicity - a standard dose of 50 mg/m² and a higher dose of 100 mg/m². Other recent studies have suggested that higher doses of some chemotherapy agents could improve both disease-free and overall survival. However, the doses received by some patients have been limited by concerns of developing cardiotoxicity, which can lead to congestive heart failure. Meta-analyses had shown that epirubicin may be associated with less cardiotoxicity than other agents in its class.

The research team enrolled 150 relapse-free patients from the FASG-05 trial who had received either standard FEC 50 (fluorouracil 500 mg/m², epirubicin 50 mg/m², cyclophosphamide 500 mg/m²) or higher dosed FEC 100 (same regimen with epirubicin 100 mg/m²) every 21 days for six cycles during adjuvant therapy for node-positive breast cancer. The blinded assessment for long-term cardiac injury was performed by a peer-review committee comprised of three cardiologists and three medical oncologists, and it included an evaluation of cardiac events occurring after the end of chemotherapy, vital signs, and concomitant disease among other cardiac parameters. This assessment occurred at a median follow-up of 102 months.

In the initial analysis, which followed the treatment phase of the FASG-05 study, researchers found that at a median follow-up of 67 months, FEC 100 produced a statistically significant improvement in 5-year disease-free (66.3% v 54.8%, P = .03) and overall survival (77.4% v 65.3%, P = .007) compared with FEC 50. A recently presented 10-year update of the FASG-05 trial showed that FEC 100 remained significantly superior to FEC 50 in terms of disease-free (P = .036) and overall survival (P = .038).

During the assessment for long-term cardiotoxicity, researchers identified two patients treated with the higher dose (FEC 100) who had well-controlled congestive heart failure that was possibly linked to treatment. An additional 18 patients had clinically asymptomatic left ventricular dysfunction, with 8 of the 18 cases probably due to treatment. None of the asymptomatic patients developed cardiac symptoms. In the patients treated with the standard dose regimen (FEC 50), one patient presented with a mild (grade 1) and asymptomatic left ventricular dysfunction for which causality was doubtful.