Joensuu H 1998.

Study characteristics
Methods	Accrual (July 1991‐April 1996) RCT ‐ Centralised randomisation Finnish Cancer registry, Helsinki Stratification according to treatment centre and WHO treatment status Multi‐centre ‐ Finland Groups well balanced on all variables
Participants	303 women with histologically verified breast cancer that had given rise to distant metastases 100% firstline Randomised no: 1) n = 153 (median age 56; 33‐72) 2) n = 150 (median age 55; 26‐72) Assessable for response: 1) n = 140 2) n = 143 Assessible for toxicity: 1) n = 151 2) n = 149
Interventions	E vs E+C+F 1)Epirubicin 20 mg/m2 iv weekly 2)Cyclophosphamide 500 mg/m2 day 1 + Epirubicin 60 mg/m2 iv day 1 of cycle + 5‐Fluorouracil 500 mg/m2 iv day 1 next cycle day 22
Outcomes	Survival and TTP curves ‐ Kaplan‐Meier product limit method ‐ from commencement of chemotherapy to death or last day of F/u Median survival 1) 16 mths 2) 18 mths Median TTP 1) 8 mths 2) 10mths OR (CR+PR) 1) 67/140 2) 79/143 Toxicity WHO 3‐4 Nausea/vomiting 1) 18/151 2) 50/149 Alopecia 1) 18/151 2) 105/149 Leukopenia 1) 16/151 2) 41/149 Toxic death ‐ NR QOL Rotterdam symptom checklist (RSCL) 285 patients.
Notes	F/U survival and TTP min 3mths (based on cycles) ‐ max 61mths (last event on the curve) **ITT analysis but survival analysis was repeated after 9 patients were found to be ineligible
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Randomisation by computer generated random digits
Allocation concealment (selection bias)	Low risk	Centrally randomised
Incomplete outcome data (attrition bias) All outcomes	Low risk	ITT analysis but survival analysis was repeated after 9 patients were found to be ineligible with the results remaining essentially similar
Selective reporting (reporting bias)	Low risk	All expected outcomes reported