| Methods |
Multicentre RCT
3 arms
Quality score: A |
| Participants |
n = 90
Median age: 62 years
Metastatic disease: 78 % (HD‐FU), 89% (HD‐FU/FA); 88% (HD‐FU/FA/Cis)
ECOG 2‐3: 8% (HD‐FU), 8% (HD‐FU/FA), 4% (HD‐FU/FA/Cis) |
| Interventions |
HD‐FU: weekly FU 3.000 mg/m² as 24‐hour infusion
versus
HD‐FU/FA: weeks dl‐FA 500 mg/m²/2 hours or l‐FA 250 mg/m²/2 hours + FU 2.600 mg/m² as 24‐hour infusion
versus
HD‐FU/FA/Cis: cisplatin 50 mg/m²/hour on days 1, 15, 29; dl‐FA 500 mg/m²/2 hours or l‐FA 250 mg/m²/2 hours; FU 2.000 mg/m²/24‐hour continuous infusion on d 1, 8, 15, 22, 29, 36. In all 3 arms, chemotherapy was administered weekly in 6 subsequent weeks, followed by 1 week rest. |
| Outcomes |
Tumour response
Median and 1‐year overall survival rates
Toxicity |
| Notes |
After stage 1 (21 patients in each arm) of the trial, the HD‐FU (single agent‐arm) arm was closed because only 2 responses had been observed. Total number of patients in this arm was 37 because inclusion was not interrupted before interim analysis. The results of the 2 combination arms were combined in the analysis. |
| Risk of bias |
| Bias |
Authors' judgement |
Support for judgement |
| Random sequence generation (selection bias) |
Low risk |
Minimisation technique |
| Allocation concealment (selection bias) |
Low risk |
Central randomisation at the EORTC data centre |
| Incomplete outcome data (attrition bias)
efficacy |
Low risk |
127/145 eligible, reasons for exclusions provided and valid |
| Incomplete outcome data (attrition bias)
safety |
Low risk |
127/145 eligible, reasons for exclusions provided and valid |
| Selective reporting (reporting bias) |
Low risk |
Report includes all expected outcomes |
| Other bias |
High risk |
Single‐therapy arm was closed earlier (Simon 2‐stage minimax design). The results of the 2 combination arms were combined in the analysis. |
| Blinded review of CT/MRI‐scans? |
High risk |
Computed tomography scans were reviewed centrally by the study co‐ordinators. |
