Background: Preclinical data have suggested a synergistic effect of cetuximab combined with gemcitabine and cisplatin and clinical data have shown a substantial improvement in response and survival when gemcitabine is combined with a platinum analogue compared with gemcitabine alone. The aim of this study was to assess the activity and feasibility of a combination of cetuximab with gemcitabine and cisplatin compared with use of gemcitabine and cisplatin alone for the treatment of advanced pancreatic cancer. Methods: In a multicentre, randomised phase II trial, 84 patients with advanced pancreatic cancer were randomly assigned to either 250 mg/m2 cetuximab weekly, after a loading dose of 400 mg/m2, plus 1000 mg/m2 gemcitabine and 35 mg/m2 cisplatin on days 1 and 8 of a 21-day cycle or to the same chemotherapeutic regimen without cetuximab. The primary endpoint was objective response (defined as the proportion of patients whose best response was either partial response or complete response). Secondary endpoints included disease control (defined as the proportion of patients whose best response was either partial response, complete response, or stable disease), progression-free survival, and overall survival. All assessments of response at each site were done blindly by a local experienced radiologist who was not directly involved in the trial. Responses were measured according to an intention-to-treat analysis. This trial is registered with the Clinical Trial registry, number NCT00536614. Findings: 29 men and 13 women were randomly assigned to cetuximab plus gemcitabine and cisplatin (median age 61 years [range 38-78]) and 22 men and 20 women were randomly assigned to gemcitabine and cisplatin (median age 64 years [range 40-76]). Seven of 40 (17·5%) patients had an objective response in the cetuximab group (95% CI 7·3-32·8) and five of 41 (12·2%) patients had an objective response in the non-cetuximab group (95% CI 4·1-26·2). No significant difference was noted between the groups both for objective response (5·3% higher in the cetuximab group [95% CI -16·5 to 27·1]; χ2 test=0·360; p=0·549) or for disease control (3·5% higher in the non-cetuximab group [-34·0% to 27·0%]; 0·446; p=0·504). Overall median follow-up was 11·8 months (range 2·5-18·5). No significant differences between the groups were noted in median progression-free survival (hazard ratio 0·96, 95% CI 0·60-1·52, p=0·847) or in median overall survival (0·91, 0·54-1·55, p=0·739): median progression-free survival was 3·4 months (95% CI 2·4-5·1) in the cetuximab group and 4·2 months (2·6-5·4) in the non-cetuximab group; median overall survival was 7·5 months (5·1-8·8) and 7·8 months (5·3-15·0), respectively. 33 patients from both groups had at least one grade 3-4 toxic effect. Interpretation: The addition of cetuximab to a combination of gemcitabine and cisplatin does not increase response or survival for patients with advanced pancreatic cancer. Although toxic effects were not increased by cetuximab, this combination should not be further assessed in phase III trials.
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