comparative phase III study using epirubicin, cyclophosphamide, 5-fluorouracil [FEC] versus adriamycin, cyclophosphamide, 5-fluorouracil [FAC] in advanced breast cancer patients

ABSTRACT

From January 1987 to April 1990, 40 patients with advanced breast cancer who either had failed non-anthracycline treatment or had no prior chemotherapy were randomised according to treatment with either epirubicin or doxorubicin in a combination chemotherapy regimen with 5-flourouracil and cyclophosphamide [FEC or FAC]. Cyclophosphamide was given in a dose of 500mg/m2 on day 1, 5-flourouracil was given in a dose of 500mg/m2 on days 1 and 8. Doxorubicin was given in a dose of 50mg/m2 on day 1 [regimen A] while epirubicin was given in two doses; 50mg/m2 [regimen B] and 75mg/m2 [regimen C] also on day 1. Cycles were repeated every 3weeks until disease progression or to cumulative doses of 550mg/m2 for doxorubicin and at least 700mg/m2 for epirubicin. The study was a comparative prospective for the overall response rate; time to progression; toxicities and dose-dependence of epirubicin. All patients were comparable in age; menopausal state; performance status; histopathology; previous treatment; site of disease and disease-free interval. As for efficacy, there was no significant difference between doxorubicin and epirubicin given in equimolar conventional doses, where the overall response rate [CR+PR] was 57% for FAC and 50% for FEC-50. The mean time to progression was 41 weeks and 39 weeks, respectively. Although high dose epirubicin [ArmC] gives an overall response rate 75% with 53 weeks mean time to disease progression, yet statistically it has no significant difference when compared to FEC-50 [ArmB]. The mean survival time for the three arms was 77 weeks for FAC; 73 weeks for FEC-50 and 111 weeks for FEC-75. As for toxicity, given in equal doses, epirubicin was less toxic than doxorubicin. Although FEC-50 was better tolerated than FEC-75, yet there was no statistical significant difference between both regimens. In its different doses ,epirubicin was less cardiotoxic than doxorubicin. Two patients under FEC developed congestive heart failure [CHF] at cumulative doses 490mg/m2 and 600 mg/m2. Although some patients treated with epirubicin [Arms B and C] received a cumulative dose reaching 1000mg/m2, yet no one developed CHF. These results indicate that epirubicin given in equimolar dose to doxorubicin is equally effective and less toxic than its parent drug. Epirubicin in higher dose proved to be well tolerated by patients and could be given to a higher cumulative dose without increasing the hematological or cardiac toxicity and meanwhile could attain a higher efficacy in patients with advanced breast cancer