FOLFIRINOX – a new paradigm in the treatment of pancreatic cancer

Abstract

Treatment of metastatic and locally advanced pancreatic cancer has made slow progress during the last decade. Single agent gemcitabine or in combination with capecitabine or erlotinib remained the preferred systemic treatment options until 2010 when the ACCORD study demonstrated significantly improved outcomes achieved with FOFIRINOX compared with gemcitabine monotherapy. Since 2010, use of FOLFIRINOX has increased both in metastatic and locally advanced cancer. Despite its gaining popularity among oncologists, unanswered questions remain. Do the often necessary dose modifications affect its efficacy? Are the toxicities manageable and how applicable are the results of the ACCORD study in the general population of patients with newly diagnosed pancreatic cancer? In the present manuscript, we review the published literature regarding the use of FOLFIRINOX, the challenges associated with its use and how it will be optimally incorporated into the management of patients with different stages of pancreatic cancer and ultimately, in a more biomarker-driven pathway algorithm.

Keywords::

• chemoradiotherapy
• chemotherapy
• clinical trials
• genomics
• pancreas cancer

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• FOLFIRINOX is the first regimen to demonstrate a median overall survival of over 11 months in patients with metastatic pancreatic cancer.

• Despite the increased toxicity of FOLFIRINOX, quality of life is not negatively affected as the benefit of disease control outweighs treatment-related toxicities.

• FOLFIRINOX is currently being assessed as neoadjuvant treatment in patients with both borderline resectable and locally advanced pancreatic cancer. Results from small cohorts are encouraging.

• FOLFIRINOX can potentially serve as a chemotherapy backbone and could be assessed in combination with novel molecularly targeted agents; however, there are concerns as to the tolerability of these regimens and how pharmacodynamically relevant doses of targeted therapy can be administered.

• Identification of biomarkers of response and increasing our understanding on the pharmacogenomics of FOLFIRINOX will aid in selecting patients more likely to benefit from aggressive upfront therapy.