Inoue 1984.

Study characteristics
Methods	Accrual dates: 01/03/1979 to not reported (date closed to accrual not reported, study closed 30/04/1983 and date submitted for publication 25/11/1983) Unknown (Japan) Sample size:58 Randomisation method: Envelope system Baseline comparability: no significant imbalance apparent or reported
Participants	Female 100% MBC 100% first line Age range: 31‐69 years Median age Arm I: 55 years, arm II: 49 years Anthracycline naive
Interventions	ACF vs ACFM Arm I: ACF doxorubicin + cyclophosphamide + ftorafur Arm II ACFM: arm I + methotrexate
Outcomes	Overall survival Response (defined as ≥ 50% reduction in tumour size) Toxicity
Notes	58/60 evaluable. 2 patients excluded (ACF arm) due to protocol violation. Survival measured from start of chemotherapy. Follow‐up details not reported. Based on accrual and date of submission: ‐ estimated minimum follow‐up 1 month ‐ estimated maximum follow‐up 51 months Time‐to‐event data extracted directly from time‐to‐event curve. Toxicity related deaths not reported.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	B ‐ Unclear
Allocation concealment (selection bias)	Low risk	A ‐ Adequate, envelope
Blinding (performance bias and detection bias) All outcomes	Unclear risk	B ‐ Unclear
Incomplete outcome data (attrition bias) Response	Low risk	A ‐ Adequate
Incomplete outcome data (attrition bias) Toxicity	Low risk	A ‐ Adequate
Incomplete outcome data (attrition bias) Overall survival	Unclear risk	B ‐ Unclear
Selective reporting (reporting bias)	Low risk	A ‐ Adequate, outcomes reported
Other bias	High risk	C ‐ 37% ACFM group had ≥3 organs involved compared to 14% in ACF group