Hoogstraten B(A)1976.

Study characteristics
Methods	Accrual (Jan 1972 ‐ Feb 1974) RCT ‐ Initial randomisation into three treatment groups with non compulsory 'crossover' following relapse or failure to respond ‐ method not described North America, multi‐centre
Participants	177 women with measurable MBC 100% MBC 100% Firstline Assessable no: 1) n = 79 2) n = 98
Interventions	A vs CMFVP‐(Intermittent) 1) Doxorubicin 60 mg/m2 iv every 3 weeks 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 then crossover
Outcomes	No OS or TTP curves OR (CR+PR) 1) 31/79 (median duration of response 4 mths) 2) 39/98 (median duration of response 10 mths) Toxicity (WHO 3‐4) Leukopenia 1) 24/79 2) 40/98 Alopecia 1) 47/79 2) 5/98 Toxic death not included as numbers cited in text and tables are inconsistent
Notes	Not ITT ‐ Of the reported accrual numbers (n=297) 14 (across all 3 arms of the trial) were not evaluable and not analysed due to protocol violations and lack of adequate data. Randomised numbers not reported by group. Phase I only considered in this review Arm 1 versus Arm 2 ‐Leukopenia was the dose limiting response
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	States 'randomised'
Allocation concealment (selection bias)	Unclear risk	Not reported
Incomplete outcome data (attrition bias) All outcomes	High risk	14 (across all 3 arms of the trial) were not evaluable and not analysed due to protocol violations and lack of adequate data.
Selective reporting (reporting bias)	High risk	All expected outcomes not reported