Ajani 2010.

Methods	Multicentre RCT 2 arms Quality score: A
Participants	n = 1053 Median age: 59 years ECOG 2‐3: 0% Metastatic disease: 96%
Interventions	S‐1+Cisplatin: S‐1 (50 mg/m2) in two daily doses d1‐21orally + cisplatin (75 mg/m2) repeated at d 28 versus FU+Cisplatin: fluorouracil (1000 mg/m2/24 hrs as 120‐hour infusion) + cisplatin (100 mg/m2), repeated at d 28 Cisplatin was discontinued after 6 cycles; provision to continue S‐1 or FU until progression of disease or unacceptable toxicities
Outcomes	Overall survival Progression‐free survival Time to treatment failure Tumour response Toxicity
Notes	Second‐line therapy in 31.4% of patients, most frequently with fluoropyrimidine
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Computer‐generated dynamic randomisation
Allocation concealment (selection bias)	Low risk	Centralised randomisation
Incomplete outcome data (attrition bias) efficacy	Low risk	Full analysis set of all treated patients (98.8% in S‐1+cisplatin arm and 94.6% in FU+cisplatin arm)
Incomplete outcome data (attrition bias) safety	Low risk	Full analysis set of all treated patients
Selective reporting (reporting bias)	Low risk	PEP: OS SEP: ORR, PFS, TTF, safety
Other bias	Low risk	None
Blinded review of CT/MRI‐scans?	Low risk	Radiographic evidence of response to treatment was also independently reviewed. An independent data monitoring committee oversaw the safety and efficacy data along with other aspects of the conduct of the study.