Narahara 2011.

Methods	Multicentre RCT 2 arms Quality score: D The study was conducted in Japan.
Participants	n = 326 Median age: 63 years Metastatic disease: 20% ECOG 2‐3: 3%
Interventions	S‐1: oral S‐1 80 mg/m²/day d 1‐28, repeated at 6 weeks S‐1 + irinotecan: oral S‐1 80 mg/m²/d d 1‐21 + irinotecan iv 80 mg/m² d 1 + 15, repeated at 6 weeks
Outcomes	Overall survival Time to treatment failure Response rates Toxicity
Notes	This study was conducted in Japan. Pre‐planned follow‐up of ≥ 1.5 years after registration of all patients was continued to 2.5 years because of a unexpectedly high survival rate of 22% at the cut‐off date after a follow‐up of 1.5 years. Second‐line chemotherapy was administered to 76% of patients.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Centralised dynamic allocation
Allocation concealment (selection bias)	Low risk	Centralised dynamic allocation
Incomplete outcome data (attrition bias) efficacy	Low risk	Full analysis set
Incomplete outcome data (attrition bias) safety	Unclear risk	4 patients found to be ineligible after starting treatment were excluded from safety analysis ‐ ?per‐protocol analysis
Selective reporting (reporting bias)	Low risk	Expected endpoints reported
Other bias	High risk	Second‐line chemotherapy was administered to a total of 76% of patients. This is likely to dilute the effect of both treatments on overall survival, but not on progression‐free‐survival.
Blinded review of CT/MRI‐scans?	Unclear risk	Extramural review is described (does not neccessarily mean blinded)