Hoogstraten 1976a.

Study characteristics
Methods	Multi‐centre randomised controlled trial. 3 arm trial. Initial randomisation into three treatment groups with non compulsory 'crossover' following relapse or failure to respond Accrual dates: Jan 1972 ‐ Feb 1974
Participants	297 pt (283 evaluable) Women with measurable metastatic BC No prior chemotherapy (except for hormones) Randomised no's ‐ Not provided Of remaining 283 evaluable pts, 97 were crossed over to phase 11 Evaluable numbers Phase 1 1) n = 79 2) n = 98 3) n = 106
Interventions	Comparison 1: A vs CMFVP‐Intermittent 1) doxorubicin 60 mg/m2 iv, 3 week cycle 2) Intermittent ‐ vincristine 0.625 mg/m2/ iv days 1 and 5 + methotgrexate 4 mg/m2/ iv dx5 + 5‐flurouracil 180 mg/m2/ iv dx5 + cyclophosphamide 120 mg/m2 iv dx5 + prednisone 40 mg/m2/day X 5 28 day cycle then crossover
Outcomes	Response (Phase 1) Toxicity
Notes	ITT not followed. 14 were invaluable and not analysed due to protocol violations and lack of adequate data. Duration of follow‐up not reported. Treatment‐related deaths were reported in the CMFVP arms due to sepsis (4), haemorrhage (2) and pulmonary embolism with associated thrombocytopenia (1). No treatment‐related deaths were reported in the doxorubicin arm, 1 patient in this arm was reported to have grade III cardiotoxicity.
Risk of bias
Bias	Authors' judgement	Support for judgement
Allocation concealment (selection bias)	Unclear risk	B ‐ Unclear