Cullinan 1994.

Methods	Multicentre RCT 4 arms Quality score: D
Participants	n = 252 Median age: 62 years ECOG 2‐3: 30%
Interventions	FAMe: 5‐FU 325 mg/m² d1‐5; adriamycin 40 mg/m² d 1, repeated at d 36; methyl‐CCNU 110 mg/m² p.o. d 1, repeated at d 71 versus FAMe+Tzt: 5‐FU 325 mg/m², d 1‐5; adriamycin 40 mg/m² d 1, repeated at d 36; triazinate 250 mg/m² d 36‐38, repeated at d 57; methyl‐CCNU 110 mg/m² p.o. d 1, repeated at d 71 versus FAP: 5‐FU 300 mg/m² d 1‐5; adriamycin 40 mg/m² d 1; cisplatin 60 mg/m² d 1, repeated at d 36 versus FU: 5‐FU 500 mg/m² d 1‐5 repeated at d 36
Outcomes	Median survival Toxicity Effects on performance status and weight gain
Notes	Three combination chemotherapy arms combined in the analysis. The single‐agent 5‐FU arm was opened after 56 participants were randomised. FAMe and FAP were closed after a planned interim analysis because of slightly higher death rate.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Not stated
Allocation concealment (selection bias)	Unclear risk	Not stated
Incomplete outcome data (attrition bias) efficacy	Low risk	Low attrition rate with long follow‐up (only 7 of 252 patients remain alive at the time of analysis)
Incomplete outcome data (attrition bias) safety	Low risk	n = 69 + 51 + 53 + 79
Selective reporting (reporting bias)	Unclear risk	Missing response rates only a small minority of patients had measurable disease so regression rate was not used as a study endpoint
Other bias	High risk	Missing information to type and follow‐up in the treatment groups, combination of 3 combination treatment arms in the analysis, 2 arms were closed after a planned interim analysis
Blinded review of CT/MRI‐scans?	Unclear risk	Not stated