A phase II randomized, placebo controlled study to evaluate the efficacy of the combination of gemcitabine, erlotinib, and metformin in patients with locally advanced or metastatic pancreatic cancer.

4021 Background: In addition to clinical data from retrospective observational studies, there is a strong preclinical rationale for a beneficial effect of metformin in cancer treatment. Therefore we conducted a randomized phase II, placebo controlled study to assess the clinical effects of metformin in pancreatic cancer. Methods: Patients with locally advanced or metastatic pancreatic cancer were randomly assigned to gemcitabine at 1000 mg/m2 on day 1, 8 and 15 q 4 weeks plus erlotinib 100 mg once daily in combination with metformin or placebo. Metformin was administered at a dose of 500 mg twice daily during the first week. If tolerated well, the dose was increased to 1000 mg twice daily. Patients were stratified according to stage of disease and the presence of diabetes. The primary endpoint was survival at 6 months. Secondary endpoints were overall survival (OS), progression free survival (PFS), objective response rate(ORR), toxicity profile, pharmacodynamics, and biomarker research. Results: A total o...