This study was designed to evaluate the cardiac safety of the combined treatment of HER2-positive metastatic
breast cancer patients with trastuzumab (Herceptin) plus epirubicin and cyclophosphamide (EC) in
comparison with EC alone in HER2-negative metastatic breast cancer patients. Patients included those with
metastatic breast cancer without any prior anti-HER2 treatment, anthracycline therapy, or any other chemotherapy
for metastatic disease. This was a nonrandomized, prospective, dose-escalating, multicenter, openlabel,
phase II study in Germany. A control group of 23 patients received EC 90/600 mg/m2 3-weekly for six
cycles (EC90 alone). A total of 26 HER2-positive patients were treated with trastuzumab, or H (2 mg/kg weekly
after an initial loading dose of 4 mg/kg), and EC 60/600 mg/m2 3-weekly for six cycles (EC60+H); another 25
HER2-positive patients received H and EC 90/600 mg/m2 3-weekly for six cycles. Asymptomatic reductions in
left ventricular ejection fraction (LVEF) of more than 10% points were detected in 12 patients (48%) treated
with EC60 + H and in 14 patients (56%) treated with EC90 + H vs 6 patients (26%) in the EC90 alone cohort.
LVEF decreases to 60%, vs 26% for EC90 alone. The interim results of this study
suggest the cardiac safety of the combination of H with EC may be greater than that of H with AC (doxorubicin
[Adriamycin]/cyclophosphamide); however, studies in larger numbers of patients are warranted. The combination
regimen revealed promising efficacy.