title: Phase II trial of metformin and paclitaxel for patients with gemcitabine-refractory advanced adenocarcinoma of the pancreas.
abstract: BACKGROUND
  In patients with adenocarcinoma of the pancreas, there are no standard second-line regimens. Many pre-clinical studies have shown that metformin alone or when combined with paclitaxel has antitumour effects on this tumour. We have tested here the combination of paclitaxel and metformin for patients with gemcitabine-refractory pancreatic cancer.
  
  
  METHODS
  An uncontrolled phase II trial was carried out based on a two-stage Simon's design, with metformin and paclitaxel for patients with locally advanced or metastatic pancreatic cancer whose disease had progressed during first line treatment with a gemcitabine-based regimen. The primary endpoint was the disease control rate at eight weeks as per response evaluation criteria in solid tumours (RECIST) 1.1. Patients received paclitaxel 80 mg/m(2) weekly for three weeks every 28 days and metformin 850 mg p.o. t.i.d. continuously until progression or intolerance state was reached.
  
  
  RESULTS
  Twenty patients were enrolled from July 2011 to January 2014: N = 6 (31.6%) achieved the primary endpoint, with all presenting stable disease. Median overall survival (OS) was 128 days (range 17-697) and the median progression free survival (PFS) was 44 days (range 14-210). Eight patients (40%) presented treatment-related G3-4 toxicities with the most common one being diarrhoea.
  
  
  CONCLUSIONS
  Despite the encouraging pre-clinical evidence of the antitumour activity of metformin in adenocarcinoma of the pancreas, the primary endpoint of the disease control rate was not met. Besides, the treatment combination was poorly tolerated and could not be studied further. This study highlights the importance of performing clinical trials to reassure preclinical or observational data.
authors: Discipline of Radiology and Oncology, Instituto do Cancer do Estado de São Paulo, Universidade de São Paulo, Brazil, Av Dr Arnaldo 251, 12º andar São Paulo, SP, 01246-000 Brazil.
authors: Maria Ignez
authors: MI
authors: Braghiroli
authors: Discipline of Radiology and Oncology, Instituto do Cancer do Estado de São Paulo, Universidade de São Paulo, Brazil, Av Dr Arnaldo 251, 12º andar São Paulo, SP, 01246-000 Brazil.
authors: Anezka C R
authors: AC
authors: de Celis Ferrari
authors: Discipline of Radiology and Oncology, Instituto do Cancer do Estado de São Paulo, Universidade de São Paulo, Brazil, Av Dr Arnaldo 251, 12º andar São Paulo, SP, 01246-000 Brazil.
authors: Tulio Eduardo
authors: TE
authors: Pfiffer
authors: Discipline of Radiology and Oncology, Instituto do Cancer do Estado de São Paulo, Universidade de São Paulo, Brazil, Av Dr Arnaldo 251, 12º andar São Paulo, SP, 01246-000 Brazil.
authors: Alexandra Kichfy
authors: AK
authors: Alex
authors: Discipline of Radiology and Oncology, Instituto do Cancer do Estado de São Paulo, Universidade de São Paulo, Brazil, Av Dr Arnaldo 251, 12º andar São Paulo, SP, 01246-000 Brazil.
authors: Daniela
authors: D
authors: Nebuloni
authors: Discipline of Radiology and Oncology, Instituto do Cancer do Estado de São Paulo, Universidade de São Paulo, Brazil, Av Dr Arnaldo 251, 12º andar São Paulo, SP, 01246-000 Brazil.
authors: Allyne S
authors: AS
authors: Carneiro
authors: Discipline of Radiology and Oncology, Instituto do Cancer do Estado de São Paulo, Universidade de São Paulo, Brazil, Av Dr Arnaldo 251, 12º andar São Paulo, SP, 01246-000 Brazil.
authors: Fernanda
authors: F
authors: Caparelli
authors: Discipline of Radiology and Oncology, Instituto do Cancer do Estado de São Paulo, Universidade de São Paulo, Brazil, Av Dr Arnaldo 251, 12º andar São Paulo, SP, 01246-000 Brazil.
authors: Luiz
authors: L
authors: Senna
authors: Discipline of Radiology and Oncology, Instituto do Cancer do Estado de São Paulo, Universidade de São Paulo, Brazil, Av Dr Arnaldo 251, 12º andar São Paulo, SP, 01246-000 Brazil.
authors: Juliana
authors: J
authors: Lobo
authors: Discipline of Radiology and Oncology, Instituto do Cancer do Estado de São Paulo, Universidade de São Paulo, Brazil, Av Dr Arnaldo 251, 12º andar São Paulo, SP, 01246-000 Brazil.
authors: Paulo Marcelo
authors: PM
authors: Hoff
authors: Discipline of Radiology and Oncology, Instituto do Cancer do Estado de São Paulo, Universidade de São Paulo, Brazil, Av Dr Arnaldo 251, 12º andar São Paulo, SP, 01246-000 Brazil.
authors: Rachel P
authors: RP
authors: Riechelmann
keywords: metformin; pancreas adenocarcinoma