The consensus report of the International Society of Gastrointestinal Oncology on the therapeutic management of advanced pancreatic cancer is commented. In the context of the available literature, a critical and methodological analysis supporting the role of cisplatin, epirubicin, 5- fluorouracil, gemcitabine (PEFG) regimen in the treatment of unresectable and metastatic pancreatic cancer is provided. In particular, the clinical relevance of the outcome observed in the phase III trial comparing PEFG regimen to standard gemcitabine is highlighted. Results of other recent trials comparing gemcitabine-erlotinib, gemcitabine-capecitabine and gemcitabine-oxaliplatin combinations to single agent gemcitabine are briefly commented from a clinical perspective.