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Randomized Phase III Trial of Gemcitabine Plus Cisplatin Compared With Gemcitabine Alone in Advanced Pancreatic Cancer

Volker Heinemann, Detlef Quietzsch, Frank Gieseler, Michael Gonnermann, Herbert Schönekäs, Andreas Rost, Horst Neuhaus, Caroline Haag, Michael Clemens, Bernard Heinrich, Ursula Vehling-Kaiser, Martin Fuchs, Doris Fleckenstein, Wolfgang Gesierich, Dirk Uthgenannt, Hermann Einsele, Axel Holstege, Axel Hinke, Andreas Schalhorn, Ralf Wilkowski

From the Medizinische Klinik und Poliklinik III, Klinikum Grosshadern; Krankenhaus Bogenhausen; Klinikum Neuperlach München; Krankenhaus München-Harlaching; Klinik für Strahlentherapie, Klinikum Grosshadern, Munich; Klinikum Chemnitz; Universitätsklinik Kiel, Kiel; Evangelisches Krankenhaus Dinslaken, Dinslaken; Klinikum Nürnberg Nord, Nürnberg; Klinikum Darmstadt, Darmstadt; Evangelisches Krankenhaus Düsseldorf, Düsseldorf; Medizinische Fakultät der TU Dresden, Dresden; Mutterhaus der Borromäerinnen Trier, Trier; Onkologische Praxis Augsburg, Augsburg; Onkologische Praxis Landshut; Klinikum Landshut, Landshut; Medizinische Universität zu Lübeck, Lübeck; Medizinische Klinik II, Universität Würzburg, Würzberg; Wissenchaftlicher Service Pharma (WiSP), Langenfeld, Germany

Address reprint requests to Volker Heinemann, MD, PhD, Medical Clinic III, Klinikum Grosshadern, Marchioninistrasse 15, 81377 Munich, Germany; e-mail: Volker.Heinemann{at}med.uni-muenchen.de

PURPOSE: To compare the effectiveness and tolerability of gemcitabine plus cisplatin with single-agent gemcitabine as first-line chemotherapy for locally advanced or metastatic pancreatic cancer.

PATIENTS AND METHODS: Patients with advanced adenocarcinoma of the pancreas were randomly assigned to receive either gemcitabine 1,000 mg/m² and cisplatin 50 mg/m² given on days 1 and 15 of a 4-week cycle (GemCis arm) or gemcitabine alone at a dose of 1,000 mg/m² on days 1, 8, and 15 of a 4-week regimen (Gem arm). The primary end point was overall survival; secondary end points were progression-free survival, response rate, safety, and quality of life.

RESULTS: One hundred ninety-five patients were enrolled and showed baseline characteristics well balanced between treatment arms. Combination treatment in the GemCis arm was associated with a prolonged median progression-free survival (5.3 months v 3.1 months; hazard ratio [HR] = 0.75; P = .053). Also, median overall survival was superior for patients treated in the GemCis arm as compared with the Gem arm (7.5 v 6.0 months), an advantage which did not, however, reach statistical significance (HR = 0.80; P = .15). Tumor response rates were comparable between treatment arms (10.2% v 8.2%). The rate of stable disease was, however, greater in the combination arm (60.2% v 40.2%; P < .001). Grade 3 to 4 hematologic toxicity did not exceed 15% in both treatment arms.

CONCLUSION: These results support the efficacy and safety of an every-2-weeks treatment with gemcitabine plus cisplatin. Median overall survival and progression-free survival were more favorable in the combination arm as compared with gemcitabine alone, although the difference did not attain statistical significance.

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

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Related Correspondence

• Gemcitabine Plus Cisplatin in Advanced Pancreatic Cancer
  Robert R. McWilliams and Steven R. Alberts
  JCO 2007 25: 1142 [Full Text]

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