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Advanced pancreatic carcinoma: current treatment and future challenges

Abstract

Pancreatic adenocarcinoma is the most lethal of the solid tumors and the fourth leading cause of cancer-related death in North America. Most patients present with locally advanced or metastatic disease that precludes curative resection. These patients have an extremely poor prognosis. In the absence of effective screening methods, considerable efforts have been made during the past decade to identify better systemic treatments. Unfortunately most trials have not shown a survival advantage for most therapies. In tandem with this increased clinical research, there has also been an expansion of preclinical laboratory investigation. These preclinical studies revealed many of the molecular mechanisms involved in pancreatic cancer development, which has provided insights into why current therapies are ineffective. These new discoveries provide some optimism that new agents inhibiting specific targets will improve outcome and overcome the resistance of pancreatic cancer to most standard treatments. We review the current standards of care for patients with locally advanced and metastatic pancreatic carcinoma and outline some future directions for the development of new treatment strategies.

Key Points

  • Pancreatic adenocarcinoma has a high propensity for locoregional invasion and early development of distant metastases

  • Approximately 80% of patients present with locally advanced or metastatic disease that precludes curative surgery, and long term survival is poor

  • In 1997 gemcitabine was established as the standard first-line treatment for patients with advanced disease based on clinical benefit and survival improvement compared with 5-fluorouracil-based chemotherapy

  • During the past decade several clinical trials assessing different cytotoxic agents and combination chemotherapy failed to improve treatment outcomes

  • The combination of a targeted agent, erlotinib, with gemcitabine resulted in a small but significant improvement in survival compared with gemcitabine alone

  • A better understanding of the biology and molecular changes that occur in pancreatic cancer will permit the development of new agents to overcome resistance

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Acknowledgements

Charles P. Vega, University of California, Irvine, CA, is the author of and is solely responsible for the content of the learning objectives, questions and answers of the MedscapeCME-accredited continuing medical education activity associated with this article.

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Stathis, A., Moore, M. Advanced pancreatic carcinoma: current treatment and future challenges. Nat Rev Clin Oncol 7, 163–172 (2010). https://doi.org/10.1038/nrclinonc.2009.236

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