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Meta-Analysis of Randomised Trials Comparing Gemcitabine-Based Doublets versus Gemcitabine Alone in Patients with Advanced and Metastatic Pancreatic Cancer

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Abstract

Objective: To evaluate the impact on overall survival at 6, 12 and 18 months of gemcitabine-based doublets compared with gemcitabine alone in patients with advanced and metastatic pancreatic cancer.

Methods: We conducted a systematic review and meta-analysis of published data on the use of gemcitabine-based doublets compared with gemcitabine alone in chemotherapy-naive patients with advanced and metastatic pancreatic cancer treated in randomised controlled phase II–III trials with overall survival as the principal or secondary endpoint. To this end, a literature search was performed using Cochrane methodology. The relative risks with 95% confidence intervals were estimated based on adjusted number of deaths and patients at risk according to the extent of follow-up and censoring. Twenty-three randomised clinical trials including 5886 patients met the inclusion criteria. In these trials, 2932 patients were randomly assigned to receive gemcitabine-based doublets and 2954 patients to receive gemcitabine alone.

Results: Gemcitabine-based doublets were associated with small but significant reductions in the risk of death at 6, 12 and 18 months of 8% (95% CI 3, 13), 4% (95% CI 2, 7) and 3% (95% CI 1, 5), respectively (p < 0.005 for all timepoints). No heterogeneity between studies was observed. Subgroup analyses showed an overall survival benefit for gemcitabine-based doublets in clinical trials testing the same planned dose intensity of gemcitabine in comparative arms, using platinum salt-based protocols and with survival as the primary endpoint.

Conclusion: This meta-analysis of data obtained from randomised controlled phase II–III trials of patients with advanced pancreatic cancer showed a small but significant improvement in overall survival for patients receiving gemcitabine-based doublets compared with gemcitabine alone.

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Acknowledgements

No sources of funding were used to assist in the preparation of this study. The authors have no conflicts of interest that are directly relevant to the content of this study.

Dr Eugeniu Banu wishes to thank those individuals whose contributions are reflected in this project: Professor Vassilis Georgoulias and Miss Dora Hatzidaki from University Hospital of Heraklion, Greece, and Professor Marc Ychou from Valdorel Cancer Centre, Montpellier, France for the updated data; and last, but not least, his family, for their support through this difficult work.

Dr Eugeniu Banu had full access to all data in this meta-analysis.

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Authors and Affiliations

  1. Medical Oncology Department, Georges Pompidou European Hospital, 20 rue Leblanc, 4th Floor, Pole B, 75908, Paris Cedex 15, France

    Eugeniu Banu, Adela Banu, Jean-Marie Andrieu & Stephane Oudard

  2. Department of Radiotherapy, European Institute of Cancer, Milan, Italy

    Andrei Fodor

  3. Hepatogastroenterology Unit, Georges Pompidou European Hospital, Paris, France

    Bruno Landi

  4. Medical Oncology Department, Ambroise Pare Hospital, Boulogne-Billancourt, France

    Philippe Rougier

  5. Clinical Research Unit, Georges Pompidou European Hospital, Paris, France

    Gilles Chatellier

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  1. Eugeniu Banu
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Correspondence to Eugeniu Banu.

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Banu, E., Banu, A., Fodor, A. et al. Meta-Analysis of Randomised Trials Comparing Gemcitabine-Based Doublets versus Gemcitabine Alone in Patients with Advanced and Metastatic Pancreatic Cancer. Drugs Aging 24, 865–879 (2007). https://doi.org/10.2165/00002512-200724100-00006

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