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Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Apr 28, 2015; 21(16): 4788-4801
Published online Apr 28, 2015. doi: 10.3748/wjg.v21.i16.4788
Metastatic pancreatic cancer: Is there a light at the end of the tunnel?
Vanja Vaccaro, Isabella Sperduti, Sabrina Vari, Emilio Bria, Davide Melisi, Carlo Garufi, Carmen Nuzzo, Aldo Scarpa, Giampaolo Tortora, Francesco Cognetti, Michele Reni, Michele Milella
Vanja Vaccaro, Sabrina Vari, Carlo Garufi, Carmen Nuzzo, Francesco Cognetti, Michele Milella, Medical Oncology A, Regina Elena National Cancer Institute, 00144 Rome, Italy
Isabella Sperduti, Medical Oncology A and Biostatistics, Regina Elena National Cancer Institute, 00144 Rome, Italy
Emilio Bria, Davide Melisi, Giampaolo Tortora, Medical Oncology, University of Verona, Azienda Ospedaliera Universitaria Integrata, 37100 Verona, Italy
Aldo Scarpa, ARC-Net Research Centre and Department of Pathology, Diagnostics and Surgery, University of Verona, 37100 Verona, Italy
Michele Reni, Medical Oncology Unit, Department of Oncology, San Raffaele Scientific Institute, 21132 Milan, Italy
Author contributions: Vaccaro V, Milella M, Bria E, Sperduti I, Garufi C, Nuzzo C and Vari S performed the literature research; Vaccaro V, Milella M and Reni M wrote the paper; Cognetti F, Scarpa A, Reni M, Milella M, Bria E, Melisi D, and Tortora G reiewed the paper; Vaccaro V and Milella M supervised the project.
Conflict-of-interest: No actual or potential conflicts of interest do exist regarding this paper. This article does not contain any studies with human or animal subjects performed by the any of the authors.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Vanja Vaccaro, MD, Medical Oncology A, Regina Elena National Cancer Institute, Via Elio Chianesi 52, 00144 Rome, Italy. vanja.vaccaro@hotmail.it
Telephone: +39-6-52666919 Fax: +39-6-52665637
Received: December 3, 2014
Peer-review started: December 4, 2014
First decision: January 8, 2015
Revised: February 8, 2015
Accepted: March 30, 2015
Article in press: March 31, 2015
Published online: April 28, 2015
Processing time: 145 Days and 15.8 Hours
Abstract

Due to extremely poor prognosis, pancreatic cancer (PDAC) represents the fourth leading cause of cancer-related death in Western countries. For more than a decade, gemcitabine (Gem) has been the mainstay of first-line PDAC treatment. Many efforts aimed at improving single-agent Gem efficacy by either combining it with a second cytotoxic/molecularly targeted agent or pharmacokinetic modulation provided disappointing results. Recently, the field of systemic therapy of advanced PDAC is finally moving forward. Polychemotherapy has shown promise over single-agent Gem: regimens like PEFG-PEXG-PDXG and GTX provide significant potential advantages in terms of survival and/or disease control, although sometimes at the cost of poor tolerability. The PRODIGE 4/ACCORD 11 was the first phase III trial to provide unequivocal benefit using the polychemotherapy regimen FOLFIRINOX; however the less favorable safety profile and the characteristics of the enrolled population, restrict the use of FOLFIRINOX to young and fit PDAC patients. The nanoparticle albumin-bound paclitaxel (nab-Paclitaxel) formulation was developed to overcome resistance due to the desmoplastic stroma surrounding pancreatic cancer cells. Regardless of whether or not this is its main mechanisms of action, the combination of nab-Paclitaxel plus Gem showed a statistically and clinically significant survival advantage over single agent Gem and significantly improved all the secondary endpoints. Furthermore, recent findings on maintenance therapy are opening up potential new avenues in the treatment of advanced PDAC, particularly in a new era in which highly effective first-line regimens allow patients to experience prolonged disease control. Here, we provide an overview of recent advances in the systemic treatment of advanced PDAC, mostly focusing on recent findings that have set new standards in metastatic disease. Potential avenues for further development in the metastatic setting and current efforts to integrate new effective chemotherapy regimens in earlier stages of disease (neoadjuvant, adjuvant, and multimodal approaches in both resectable and unresectable patients) are also briefly discussed.

Keywords: Pancreatic cancer; Metastatic disease; Chemotherapy; Folfirinox; nab-Paclitaxel

Core tip: In this paper, we provide an overview on the latest progress in the systemic treatment of advanced pancreatic cancer, mostly focusing on recent findings that have set new standards in metastatic disease. Potential avenues for further development in the metastatic setting and current efforts to integrate new effective chemotherapy regimens in earlier stages of disease (neoadjuvant, adjuvant, and multimodal approaches in both resectable and unresectable patients) are also briefly discussed.