1. ¹Cancer Research UK Clinical Trials Unit, University of Birmingham, Birmingham, UK
2. ²University of Heidelberg, Heidelberg, Germany
3. ³Agia Olga Hospital, Athens, Greece
4. ⁴University of Verona, Verona, Italy
5. ⁵University Hospital Rotterdam, Rotterdam, The Netherlands
6. ⁶University of Bergen, Bergen, Norway
7. ⁷Teikyo University School of Medicine, Teikyo, Japan
8. ⁸University of Liverpool, Liverpool, UK

Correspondence: Professor JP Neoptolemos, Department of Surgery, Royal Liverpool University Hospital, 5th floor UCD Building, Daulby Street, Liverpool L69 3GA, UK. E-mail: j.p.neoptolemos@liverpool.ac.uk

⁹For Pancreatic Meta-analysis Group see Appendix A

Received 1 November 2004; Revised 14 February 2005; Accepted 15 February 2005; Published online 5 April 2005.

Abstract

The aim of this study was to investigate the worldwide evidence of the roles of adjuvant chemoradiation and adjuvant chemotherapy on survival in potentially curative resected pancreatic cancer. Five randomised controlled trials of adjuvant treatment in patients with histologically proven pancreatic ductal adenocarcinoma were identified, of which the four most recent trials provided individual patient data (875 patients). This meta-analysis includes previously unpublished follow-up data on 261 patients. The pooled estimate of the hazard ratio (HR) indicated a 25% significant reduction in the risk of death with chemotherapy (HR=0.75, 95% confidence interval (CI): 0.64, 0.90, P-values_stratified (P_strat)=0.001) with median survival estimated at 19.0 (95% CI: 16.4, 21.1) months with chemotherapy and 13.5 (95% CI: 12.2, 15.8) without. The 2- and 5-year survival rates were estimated at 38 and 19%, respectively, with chemotherapy and 28 and 12% without. The pooled estimate of the HR indicated no significant difference in the risk of death with chemoradiation (HR=1.09, 95% CI: 0.89, 1.32, P_strat=0.43) with median survivals estimated at 15.8 (95% CI: 13.9, 18.1) months with chemoradiation and 15.2 (95% CI: 13.1, 18.2) without. The 2- and 5-year survival rates were estimated at 30 and 12%, respectively, with chemoradiation and 34 and 17% without. Subgroup analyses estimated that chemoradiation was more effective and chemotherapy less effective in patients with positive resection margins. These results show that chemotherapy is effective adjuvant treatment in pancreatic cancer but not chemoradiation. Further studies with chemoradiation are warranted in patients with positive resection margins, as chemotherapy appeared relatively ineffective in this patient subgroup.