Creech 1979.

Study characteristics
Methods	Randomised controlled trial. No information on randomisation provided. Pts were stratified according to 'poor' or 'good' risk Baseline comparability achieved.
Participants	78 pts. Women with visceral metastatic breast cancer. No prior cytotoxic chemotherapy Age range: 34‐79 yrs in CAMF arm; 32‐87 yrs in CMF arm. Median age: 56 yrs both arms
Interventions	CAMF vs CMF Arm A: CAMF cyclophosphamide 50mg/m2 po, days 1‐14; doxorubicin 20mg/m2 iv, days 1, 8; methotrexate 20mg/m2 iv, days 1, 8; 5‐fluorouracil 300mg/m2 iv, days 1, 8. 28 day cycle. Arm B: CMF cyclophasphamide 50mg/m2 po, days 1‐14; methotrexate 20mg/m2 iv, days 1, 8; 5‐fluoruoracil 300mg/m2 iv, days 1, 8. 28 day cycle. Cycles continued until progression. CMF arm received doxorubicin 20mg/m2, iv days 1,8 after progression. Doxorubicin ceased after a maximum culmulative dose of 550 mg/m2 reached.
Outcomes	Response (ECOG) Survival (reported by response status) Progression‐free survival (reported by response status) Toxicity
Notes	Randomised controlled trial of 2 low dose regimens. CMF pts crossed over to low dose Doxorubicin on progression. ITT analysis followed. Estimated min f/up = Estimated min f/up = 5months (median time to progression), max follow‐up = 39 months (from survival curve). Overall survival and time to progression were reported for subsets of pts by response status and not extracted for meta‐analysis. No statistically significant differences between CAMF and CMF were reported for time to event data. Median survival for PR/CR pts was 20 months in CAMF arm vs 19 months in CMF arm. Treatment related deaths were not reported. No cardiotoxicity was observed in either arm.
Risk of bias
Bias	Authors' judgement	Support for judgement
Allocation concealment (selection bias)	Unclear risk	B ‐ Unclear