Systemic therapy of advanced pancreatic cancer: has the landscape changed?

Limited progress has been made in the treatment of advanced pancreatic cancer. Gemcitabine was established as a standard of care after a randomized phase III study showed an improvement in clinical benefit response and overall survival over 5-flurouracil. Multiple phase III studies have been conducted to improve upon the response and survival established with single-agent gemcitabine. Combining different cytotoxic chemotherapy with gemcitabine failed to provide any meaningful survival advantage over gemcitabine monotherapy. A modest improvement in overall survival was noted when an epidermal growth factor receptor tyrosine kinase inhibitor (erlotinib) was added to gemcitabine. The landscape for the treatment of advanced pancreatic cancer changed with the introduction of the fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) regimen at the 2010 American Society of Clinical Oncology meeting. The phase III clinical trial showed an overall survival improvement in the gemcitabine group of 6.8 months compared to 11.1 months in the FOLFIRINOX arm (P<.0001). More interestingly, almost half of the patients in the FOLFIRINOX group were alive after 1 year, and the response rate was 31.6%. A new triplet chemotherapy regimen has emerged to replace the use of single-agent gemcitabine in a highly selected patient population. In this article, we will review the published data on first-line chemotherapy, with discussion of targeted agents for advanced pancreatic cancer and potential future directions.