Doubling epirubicin dose intensity (100 mg/m2 versus 50 mg/m2) in the FEC regimen significantly increases response rates. An international randomised phase III study in metastatic breast cancer

Purpose: A phase III study was performed in patients with metastaticbreast cancer (MBC) to evaluate the effect on response rate and survival ofa doubling of the epirubicin dose intensity.Patients and methods: Four hundred fifty-six patients were randomisedto receive either epirubicin 100 mg/m² or 50mg/m² in combination with 5-FU (500 mg/m²) andcyclophosphamide (500 mg/m²) (FEC 100 vs. FEC 50) i.v., every21 days for a maximum of six cycles (eight in case of CR).Results: Of 456 patients, 390 were evaluable for efficacy. Objectiveresponse (CR + PR) was seen in 57% (FEC 100) vs. 41% (FEC 50)of the evaluable patients (P = 0.003). The CR rate was higher in the FEC100 arm (12% vs. 7%, P = 0.07). FEC 100 producedsignificantly higher response rates in patients with visceral localisation(50% vs. 34%, P = 0.011) and in patients with more thantwo metastatic organ sites (64% vs. 37%, P = 0.001).Median time to progression (7.6 vs. 7 months) and overall survival (18 monthsvs. 17 months) were similar. Myelosuppression was the principal toxic effect,with grade IV neutropenia observed in 57% of the patients treated withFEC 100 vs. 9% of those on FEC 50. Grade IV infection or febrileneutropenia were observed in 8% (FEC 100) vs. 0.4% (FEC 50), butthe incidence of septic death was the same in the two arms (two patientseach). Cardiac toxicity was similar in the two treatment groups, with5% vs. 3% of the patients taken off study due to cardiac events,primarily due to a decline in LVEF. Only three patients (two in FEC 100)experienced congestive heart failure.Conclusion: This trial shows that FEC with epirubicin at 100mg/m² can be administered for repeated cycles without bonemarrow support with increased, though acceptable, toxicity and with asignificant increase of antitumor effect (especially in visceral and/orhigh-burden disease), but no increased survival.