Nielsen D 2000.

Study characteristics
Methods	Accrual (July 1987‐Nov 1990). Phase III RCT. Consecutive patients were centrally registered and then randomised after stratification by ECOG performance status Denmark Groups comparable on age, performance status, prior adjuvant therapy, menopausal status, sites and number of metastatic sites, disease free interval to first recurrence and lead time from prior adjuvant chemotherapy
Participants	155 women with histologically proven locally advanced or MBC and bidemensionally measurable disease 92% MBC 100% Firstline Randomised no: 1) n = 81 (median age 52; 34‐68) 2) n = 74 (median age 55; 27‐69) Assessable no: 1) n = 74 2) n = 65
Interventions	E vs E+ CDDP 1) Epirubicin 70 mg/m2 days 1 and 8 every 4 weeks 2) Epirubicin 60mg/m2 days 1and 8 + Cisplatin 100mg/m2 day 1 every 4 weeks
Outcomes	Survival and TTP curves ‐ Kaplan Meier estimate. TTP calculated as time from first drug administration Median survival 1) 15.1 mths (0.1‐63.3) 2) 21.5 mths (21.5 (0.1‐77.7) Median TTP 1) 8.4 mths (0.1‐66.3) 2) 15.3 mths (0.1‐77.7) OR (CR+PR) 1) 45/74 2) 43/65 Toxicity WHO 3‐4 WCC 1) 59/74 2) 60/65 Toxic death 1) 2 2) 4
Notes	FU survival and TTP min 1mth ‐ max 77.7 mths based on text ITT for response, survival and toxicity ‐ although 10 declared ineligible, 6 refused treatment. No loss to follow up
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Centrally randomised but method not described
Allocation concealment (selection bias)	Low risk	Centrally randomised
Incomplete outcome data (attrition bias) All outcomes	Low risk	No missing outcome data
Selective reporting (reporting bias)	Low risk	All expected outcomes reported