Heidemann E 2002.

Study characteristics
Methods	Accrual (1992‐1997) RCT ‐ Random number generation ‐ central statistical institute ‐ stratified according to disease free state and metastases Germany, multi‐centre Groups well balanced except for receptor status
Participants	260 women with measurable metastatic BC fulfilling high risk criteria previously untreated for MBC Histologically documented ABC stage IV Anthracycline naive 100% MBC 100% Firstline Randomised no: 1) 127 2) 133 Evaluable for efficacy and QOL 1) 119 2) 119 Evaluable for toxicity 1) 131 2) 125
Interventions	MZA vs FEC 1) Mitoxantrone 12 mg/m2 IV by short infusion x21 days 2) FEC 5‐Flurouracil 500 mg/m2 IV + Epirubicin 50 mg/m2 + Cyclophosphamide 500 mg/m2 IV every 3 weeks, max 12 cycles 2nd and 3rd line treatment fixed
Outcomes	Survival and TTP curves ‐ Kaplan‐Meier life table method ‐ from commencement of treatment Median survival 1) 14.1 mths 2) 15.8 mths Median TTP 1) 4.4 mths 2) 6.15 OR (CR + PR) 1) 30/119 2) 43/119 Toxicity (WHO 3‐4) Nausea /vomiting 1) 9/131 2)37/125 Alopecia 1)6/131 2) 77/125 Toxic death ‐ NR QOL ‐ Brunners score
Notes	F/U survival and TTP min 0.99 ‐ max 73.68mths (Stated in text)
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Random number generation
Allocation concealment (selection bias)	Low risk	Centrally randomised
Incomplete outcome data (attrition bias) All outcomes	Low risk	Quorum of missing patients provided ‐ balanced across both groups unlikely to have a clinically relevant impact
Selective reporting (reporting bias)	Low risk	All expected outcomes reported