Epirubicin-containing Regimens Reported to Prolong Survival in Breast Cancer Patients

MUNICH, Germany—‘‘Epirubicin-containing regimens significantly prolong relapse-free and overall survival rates compared with standard regimens” for treating breast cancer, Michael Untch, MD, reported at a clinical investigators’ workshop. ‘‘The dose-response relationship for epirubicin,” he continued, “translated into significant improvements in outcome, and dose-intensification of epirubicin and paclitaxel was well tolerated.”

Dr. Untch is Chief of the Breast Cancer Service at the University of Munich, Germany. The workshop was sponsored by the University of Texas M. D. Anderson Cancer Center and by Pharmacia Oncology.

French Study Reviewed

Dr. Untch reviewed several trials of epirubicin (Ellence)-based combination therapy including the French Adjuvant Study Group trial comparing the FEC-100 and FEC-50 regimens in 565 breast cancer patients with positive axillary nodes. Both of these regimens include 5-fluorouracil at 50 mg/m² and cyclophosphamide (Cytoxan) at 500 mg/m² plus epirubicin at either 100 or 50 mg/m².

Five-year disease-free survival was 65% with FEC-100 vs 52% with FEC-50 (P = .007). This constitutes a relative risk reduction of 32%, Dr. Untch noted.

Dr. Untch and colleagues have also studied epirubicin/cyclophosphamide (EC) in patients with 10 or more positive nodes. At follow-up of 42 months, the improvement in overall survival with dose-intensified epirubicin (120 mg/m²) vs standard epirubicin (90 mg/m²), followed by CMF (cyclophosphamide, methotrexate, 5-FU), has reached borderline significance (P = .06).

“I am positive that with dose-intense EC, we can help these patients to prevent metastatic disease and improve disease-free and overall survival,” Dr. Untch said.

Phase III Intergroup Study

A phase III intergroup study in patients with 4 to 9 positive nodes compares epirubicin 150 mg/m² followed by paclitaxel (Taxol) 225 mg/m², and cyclophosphamide 2,500 mg/m², all drugs given biweekly, to epirubicin 90 mg/m², cyclophosphamide 600 mg/m² followed by paclitaxel 175 mg/m², triweekly. Current toxicity data from this trial were presented at this year’s American Society of Clinical Oncology meeting and showed that the epirubicin/paclitaxel regimen is both tolerable and active in these patients. Next is a trial of epirubicin plus cyclophosphamide, followed by paclitaxel as neoadjuvant therapy, then followed by surgery and standard CMF as adjuvant therapy.

Dr. Untch said that epirubicin is also being studied in combination with trastuzumab (Herceptin) in HER2/neu-positive metastatic patients. Epirubicin is less cardiotoxic than doxorubicin (Adriamycin), and the hope is that it can be combined safely with the monoclonal antibody treatment.