| Methods |
Multicentre RCT
2 arms
Quality score: D |
| Participants |
n = 337
Median age: 59 years
Metastatic disease: 95.5% |
| Interventions |
IF: irinotecan 80 mg/m² i.v.; FA 500 mg/m² i.v.; 5‐FU 2000 mg/m² as a 22‐hour continuous infusion on d 1 weekly for 6 weeks, followed by 1 week rest
versus
CF: cisplatin 100 mg/m² i.v. d 1; 5‐FU 1000 mg/m²/day as 24‐hour continuous infusion d 1–5, repeated at 4 weeks |
| Outcomes |
Hazard ratios and median survival for overall survival and time to progression, tumour response, toxicity, QoL |
| Notes |
The trial was planned to establish superiority or non‐inferiority of IF over CF. Patients have finished prior radiotherapy and surgery 6 and 3 weeks, respectively, before randomisation. Previous adjuvant or neo‐adjuvant chemotherapy was allowed if completed 12 months before first relapse. |
| Risk of bias |
| Bias |
Authors' judgement |
Support for judgement |
| Random sequence generation (selection bias) |
Low risk |
Biased coin method |
| Allocation concealment (selection bias) |
Unclear risk |
Not stated |
| Incomplete outcome data (attrition bias)
efficacy |
Low risk |
Analysis of the full‐analysis population of treated patients |
| Incomplete outcome data (attrition bias)
safety |
Low risk |
Analysis of the full‐analysis population of treated patients |
| Selective reporting (reporting bias) |
Low risk |
Report includes all expected outcomes |
| Other bias |
High risk |
Rate of non‐evaluable response was imbalanced between arms (IF 9.4% versus CF 16.8%), largely due to the higher rate of early discontinuations for toxicity in the CF arm. This difference may result from closer follow‐up in IF. Prior radiotherapy and chemotherapy were allowed under certain circumstances. |
| Blinded review of CT/MRI‐scans? |
Low risk |
An External Radiological Review Committee (ERRC), blinded to treatment arm, reviewed all disease assessments and determined evaluability for response and date of progression. |
