Trial one and two contained premenopausal node-positive women with breast cancer, Trial three pre- and postmenopausal women with node-positive or negative breast cancer. It was discovered that FEC is at least as effective as CMF in premenopausal women with node positive- or negative breast cancer and that FEC produced no additional benefit in terms of 5-year relapse-free or overall survival. Dose response
Researchers discovered a benefit for epirubicin 100 mg (FEC 100) over epirubicin 50 mg (FEC 50). Patients with FEC100 treatment of the study were relapse-free and an overall survival rate at 5 years higher as in FEC 50 treatment. They also compared epirubicin 90 mg/m2 (EC 90) with epirubicin 120 mg/m2 (EC 120). After a mean follow up of 27 months elapse-free survival of patients who received EC 120 was significantly longer than that of patients who received EC 90. The combination of Epirubicin and tamoxifen lead to an increase survival in node-positive postmenopausal women with hormone receptor-positive breast tumours. Advanced breast cancer
First-line therapy
Epirubicin monotherapy was shown to be therapeutically equivalent to doxorubicin monotherapy in patients who had to receive previous chemotherapy for advanced breast cancer. There are several Combination therapies: 1. FEC: fluorouracil + cyclophosphamide + epirubicin; 2. FAC: fluorouracil + cyclophosphamide + doxorubicin. The median survival rates markedly better than those achieved with epirubicin monotherapy. Additionally the FEC treatment seems to be less toxic.
Epirubicin is also capable of generating cytotoxic free radicals, which are very reactive against DNA, cell membranes and mitochondria.Epirubicin exhibits activity in all phases of the cell cycle, but maximal cell kill occurs during the S and G2 phases of the cell cycle. Pharmacokinetics
The pharmacokinetic properties of epirubicin can be described by a 3-compartment model, with half-lives for the initial (alpha), intermediate (beta) and terminal (gamma) elimination phases of approximately 3 minutes, 1 hour and 30 hours, respectively. Only the latter differs substantially compared to doxorubicin, as the terminal elimination half-life of doxorubicin is estimated to be approximately 40-70% longer than that of epirubicin. The pharmacokinetics of epirubicin appear to be linear for doses in the range of 40 – 150 mg/m2.The volume of distribution of epirubicin is found to be high and variable (1 000- 1 500), but similar to those reported for doxorubicin. This indicates extensive distribution into the tissue. The total plasma clearance of epirubicin is approximately 45 to 50 L/h/m2, which is almost 2-fold higher than that of doxorubicin. Area under the plasma concentration versus time curve values (adjusted for dose) are 1.3 to 1.7 times higher for doxorubicin than epirubicin following single-dose intravenous administration. Epirubicin shows a 77% binding to plasma proteins, predominantly albumin, which is not affected by drug concentration. Metabolism
Epirubicin is rapidly metabolized by the liver to relatively or totally inactive metabolites: epirubicinol, 2 glucuronides and 4 aglycones.