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Meta-Analyses of Chemotherapy for Locally Advanced and Metastatic Pancreatic Cancer

Asma Sultana, Catrin Tudur Smith, David Cunningham, Naureen Starling, John P. Neoptolemos, Paula Ghaneh

From the Cancer Research UK Liverpool Cancer Trials Unit and Centre for Medical Statistics and Health Evaluation, University of Liverpool, Liverpool; and Royal Marsden Hospital, Surrey, United Kingdom

Address reprint requests to Paula Ghaneh, MD, Division of Surgery and Oncology, School of Cancer Studies, 5th Floor–UCD Building, Daulby St, Liverpool, Merseyside L69 3GA, United Kingdom; e-mail: p.ghaneh{at}liv.ac.uk

Purpose There are a large number of randomized controlled trials involving chemotherapy in the management of advanced pancreatic cancer. Several chemotherapeutic agents, either alone or in combination with other chemotherapy or novel agents, have been used. The aim of these meta-analyses was to examine the different therapeutic approaches, and the comparisons examined were as follows: chemotherapy versus best supportive care; fluorouracil (FU) versus FU combination chemotherapy; gemcitabine versus FU; and gemcitabine versus gemcitabine combination chemotherapy.

Methods Relevant trials were identified by searching databases, trial registers, and conference proceedings. The primary end point was overall survival.

Results One hundred thirteen randomized controlled trials were identified, of which 51 trials involving 9,970 patients met the inclusion criteria. Chemotherapy improved survival compared with best supportive care (hazard ratio [HR] = 0.64; 95% CI, 0.42 to 0.98). FU-based combination chemotherapy did not result in better overall survival compared with FU alone (HR = 0.94; 95% CI, 0.82 to 1.08). There was insufficient evidence of a survival difference between gemcitabine and FU, but the wide CI includes clinically important differences in both directions, making a clear conclusion difficult (HR = 0.75; 95% CI, 0.42 to 1.31). Survival was improved after gemcitabine combination chemotherapy compared with gemcitabine alone (HR = 0.91; 95% CI, 0.85 to 0.97).

Conclusion There was a significant survival benefit for chemotherapy over best supportive care and gemcitabine combinations over gemcitabine alone. This supports the use of gemcitabine-based combination chemotherapy in the treatment of advanced pancreatic cancer.

Supported by Cancer Research UK.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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