PurposeThe separate impacts of dose and dose intensity of chemotherapy for metastatic breast cancer remain uncertain. The primary objective of this trial was to compare a short, high-dose, intensive course of epirubicin and cyclophosphamide (EC) with a longer conventional dose regimen delivering the same total dose of chemotherapy.MethodsThis open label trial randomised 235 women with metastatic breast cancer to receive either high-dose epirubicin 150mg/m(2) and cyclophosphamide 1500mg/m(2) with filgrastim support every 3 weeks for 3 cycles (HDEC) or standard dose epirubicin 75mg/m(2) and cyclophosphamide 750mg/m(2) every 3 weeks for 6 cycles (SDEC). Primary outcomes were time to progression, overall survival and quality of life.ResultsIn 118 patients allocated HDEC 90% of the planned dose was delivered, compared to 96% in the 117 participants allocated SDEC. There were no significant differences in the time to disease progression (5.7 vs. 5.8 months, P=0.19) or overall survival (14.5 vs. 16.5 months, P=0.29) between HDEC and SDEC, respectively. Patients on HDEC reported worse quality of life during therapy, but scores improved after completion to approximate those reported by patients allocated SDEC. Objective tumour response was recorded in 33 (28%) on HDEC and 42 patients (36%) on SDEC. HDEC produced more haematologic toxicity.ConclusionFor women with metastatic breast cancer, disease progression, survival or quality of life were no better with high-dose intensity compared to standard dose EC chemotherapy.Australian Clinical Trials Registry registration number ACTRN12605000478617.