Ahmann DL 1974(1).

Study characteristics
Methods	RCT ‐ consecutive candidates for cytotoxic treatment at the clinic Baseline comparability
Participants	43 women with MBC confirmed histopathologically and suitable for serial measurement 100% MBC 100% Firstline Postmenopausal Randomised and assessable no: 1) n = 22 2) n = 21
Interventions	CCNU (Lomustine) vs F+C+P+/‐ V1 1) Methyl CCNU 225mg/sq MPO day 1 2) 5 Fluorouracil 8mg daily IV for 5 days + Cyclophosphamide 4mg daily IV for 5 days + Prednisone PO 30 mg 2/52, 20mg 3rd week, 10mg thereafter plus or minus Vincristine 1.4mg/m2 IV day 1 and 5 (11 patients from group 2)
Outcomes	Survival curve ‐ ascertained from associated paper ‐ Kaplan‐Meier estimate Median survival 1) 11.7 mths (9.1 ‐15.5 mths) 2) 18.6 mths (9.3 ‐ 25.1 mths) Response 1) 1/22 2) 12/21 Toxicity data ‐ NE One death (adriamycin arm) ‐ post mortum did not find attributable to treatment.
Notes	F/U ‐ min 1.8mths (rounded up to 2mths (based on 2 cycles) ‐ max 120mths (estimated from curve) First of three trials ‐ with a combined total of 131 patients. Crossover at progression of disease ‐ 11/21 to Vincristine from group 2 All patients included in the analysis for all three trials ‐ all but one patient observed till death (still alive at time of report) Pooled data from all 3 trials also analysed ‐ single versus combination therapy but not used in this review
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	High risk	Publication states Patients were consecutive candidates for cytotoxic treatment at the clinic. It is unclear if this means consecutively sampled or consecuetively allocated
Allocation concealment (selection bias)	Unclear risk	Not reported
Incomplete outcome data (attrition bias) All outcomes	Low risk	No missing outcome data
Selective reporting (reporting bias)	Unclear risk	Insufficient information to fully assess