Waddell 2013.
Methods | UK multicenter RCT (63 centers in UK), Phase III | |
Participants |
Number of participants: 553 patients June 2008 to October 2011) Number randomised: Experimental group (epirubicin and oxaliplatin and capecitabine (EOC) + panitumumab): 278 control group (EOC): 275 Number evaluated: Experimental group: 278, age (median and range): 62 (26 ‐ 83) years Control group: 275, age (median and range): 63 (26 ‐ 83) years Diagnosis: patients with histologically‐verified, untreated, metastatic or locally‐advanced inoperable adenocarcinoma or undifferentiated carcinoma of the esophagus, gastro‐esophageal junction, or stomach. Inclusion: eligible patients should: be > 18 years; have measurable disease on CT or MRI; WHO performance status of 0 – 2; adequate cardiac, renal, liver, and bone marrow function |
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Interventions |
Experimental group : epirubicin 50 mg/m² i.v. on day 1, every 3 weeks; oxaliplatin 100 mg/m² i.v. on day 1 every 3 weeks; oral capecitabine 1000 mg/m² per day on day 1 – 21 every 3 weeks; and panitumumab 9 mg/kg i.v. on day 1, every 3 weeks Control group: epirubicin 50 mg/m² i.v.on day 1 every 3 weeks; oxaliplatin 130 mg/m² i.v. on day 1 every 3 weeks; and oral capecitabine 1250 mg/m² per day on days 1 – 21 every 3 weeks Participants received a maximum of 8 cycles of treatment |
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Outcomes |
Duration of follow‐up (median): 5.3 months (IQR: 2.6 ‐ 9.5) for experimental group, and 4.6 months (IQR: 1.8 ‐ 10.1) for control group OS, PFS, overall response, adverse events (only the incidence for grade ≥ 3 adverse events was reported, not for any adverse events) |
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Notes | Sponsor: Royal Marsden NHS Foundation Trust Study closed early due to lack of efficacy |
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Risk of bias | ||
Bias | Authors' judgement | Support for judgement |
Random sequence generation (selection bias) | Low risk | "Randomisation was done independently at the Institute for Cancer Research Clinical Trials and Statistics Unit (ICR‐CTSU) by random permuted blocks (block sizes of six and eight) and stratified by centre region (locations were divided into 11 regions), extent of disease (locally advanced vs metastatic disease), and performance status (0 vs 1 vs 2)" |
Allocation concealment (selection bias) | Low risk | "Patients were enrolled by trials office staff at the Royal Marsden Hospital, who then faxed confirmation of the allocated treatment group to local site staff" |
Blinding of participants and personnel (performance bias) All outcomes | High risk | The open‐label design may introduce performance bias (e.g. through stress‐related mechanisms). |
Blinding of outcome assessment (detection bias) OS, Serious adverse events | Low risk | These outcomes were unlikely to be affected by the blinding status of assessors |
Blinding of outcome assessment (detection bias) PFS, Response, quality of life & adverse events | Unclear risk | No masking for outcome assessors, but quality of reported data was controlled by trust‐appointed monitoring staff or central monitoring system |
Incomplete outcome data (attrition bias) All outcomes | Low risk | ITT analysis was used |
Selective reporting (reporting bias) | Low risk | Prior protocol was available |
Other bias | Unclear risk | Study closed early due to lack of efficacy |