Pancreatic cancer (PC) incidence rates are rapidly increasing in developed countries, with half the patients being metastatic at diagnosis. For decades, fluorouracil, then gemcitabine regimens were the preferred palliative first-line options for fit patients with metastatic PC. FOLFIRINOX (a combination of bolus and infusional fluorouracil, leucovorin, irinotecan and oxaliplatin) was introduced to clinical practice in 2010 due to the results of the phase II/III trial (PRODIGE 4/ACCORD 11) comparing FOLFIRINOX with single-agent gemcitabine as first-line treatment for patients with MPC. Median overall survival, progression-free survival, and objective response rate were superior with FOLFIRINOX over gemcitabine and there was prolonged time to definitive deterioration in quality of life. Although FOLFIRINOX was also associated with increased toxicity, mainly febrile neutropenia and diarrhea, there has been rapid uptake of this regimen. This review closely examines optimal management and prevention of toxicities, international recommendations for first-line treatment, and use of modified FOLFIRINOX protocols. In this review, we also look at the potential benefit of FOLFIRINOX in selected groups of patients: second-line therapy, adjuvant chemotherapy, induction therapy in patients with borderline resectable and locally advanced PC. Robust validation of the FOLFIRINOX regimen in these settings requires confirmation in further randomized trials.
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