Researchers from Europe affiliated with the Herceptin® (trastuzumab), Cytoxan® (cyclophosphamide), and Ellence® (epirubicin) (HERCULES) trial have reported that this regimen is effective and tolerable for women with newly diagnosed HER2-positive (HER2+) metastatic breast cancer. The details of this study were published in the March 20, 2010 issue of the Journal of Clinical Oncology.1

The combination of an anthracycline and Herceptin is often associated with an increased rate of cardiotoxicity and congestive heart failure. This has led to combining Herceptin with other active agents for the treatment of breast cancer. However, anthracyclines are among the most useful agents for the treatment of breast cancer. Herceptin has been combined with non-cardiotoxic agents such as Navelbine® (vinorelbine), Taxotere® (docetaxel), Taxol® (paclitaxel), Platinol® (cisplatin), and Paraplatin® (carboplatin). More recently, Doxil® (pegylated liposomal doxorubicin) has been combined successfully with Herceptin with no increase in cardiac problems.

Ellence is an anthracycline commonly used in Europe with a better toxicity profile than Adriamycin® (doxorubicin), which is more commonly used in the United States. Ellence-based regimens appear to be more effective than Adriamycin-based regimens for breast cancer. Most women with breast cancer in the United States, however, receive an anthracycline-based adjuvant regimen.

The current study involved 120 patients with HER2+ metastatic breast cancer who were treated with Ellence, Cytoxan, and Herceptin. Patients were randomly allocated to receive Ellence at a dose of 60 mg/m2 or 90 mg/m2. A third group of patients with HER2-negative breast cancer received Ellence at a dose of 90 mg/m2 and Cytoxan without Herceptin. The main endpoint of this study was dose-limiting cardiotoxicity (DLC).

• The incidence of DLC was 5.0% for patients receiving the 60 mg/m3 dose of Ellence and 1.7% for patients receiving the 60 mg/m2 dose. Patients not receiving Herceptin had 0% DLC.
• There were no cardiac-related deaths in any group.
• The overall response rate in patients with HER2+ breast cancer receiving 90 mg/m2 dose of Ellence was 57% compared with 60% for patients receiving the 60 mg/m2 dose.
• Time to tumor progression was 12.5 months for patients with HER2+ breast cancer receiving the 90 mg/m2 dose of Ellence compared with 10.1 months in patients receiving the 60 mg/m2 dose.

These authors reported: “The HEC [Ellence, Cytoxan, and Herceptin] regimen is a promising treatment option for patients with HER2-positive [metastatic breast cancer]. The lower incidence of DLC with HEC, compared with historical incidence associated with trastuzumab plus doxorubicin, supports further evaluation of this regimen, especially in adjuvant or neoadjuvant settings.”

Comments: These results suggest that Ellence has less cardiotoxicity than Adrimycin when given with Herceptin.

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