From the Guidelines
FOLFIRINOX is the preferred first-line treatment for patients with pancreatic cancer and good performance status (ECOG 0-1), as it has been shown to improve median progression-free survival and overall survival compared to gemcitabine alone 1. The regimen combines four medications: FOL (folinic acid or leucovorin), F (fluorouracil or 5-FU), IRIN (irinotecan), and OX (oxaliplatin). Typically administered intravenously every two weeks, a standard cycle includes oxaliplatin (85 mg/m²) over 2 hours, followed by leucovorin (400 mg/m²) over 2 hours, with irinotecan (180 mg/m²) given during the same 90-minute period. This is followed by 5-FU as both a bolus (400 mg/m²) and then as a continuous infusion (2400 mg/m²) over 46 hours.
Some key points to consider when using FOLFIRINOX include:
- Close monitoring for side effects, which can be significant and include neutropenia, diarrhea, neuropathy, fatigue, and nausea
- Reserving the regimen for patients with good performance status (ECOG 0-1) and adequate organ function
- The mechanism of action, which involves oxaliplatin damaging DNA, irinotecan inhibiting topoisomerase I, and 5-FU (enhanced by leucovorin) disrupting DNA synthesis
It's also important to note that FOLFIRINOX has been shown to be effective in patients with locally advanced pancreatic cancer, with a pooled median overall survival of 24.2 months (95% CI, 21.7–26.8) in a systematic review of 11 studies and 315 patients 1. Additionally, a subsequent therapy option for patients with good performance status and disease progression is 5-FU + leucovorin + irinotecan (FOLFIRI), which has been shown to have comparable efficacy and safety to mFOLFOX in patients with metastatic disease who have failed previous gemcitabine treatment 1.
However, the most recent and highest quality study, the PRODIGE trial, supports the use of FOLFIRINOX as a first-line treatment, with significant improvements in median progression-free survival (6.4 vs 3.3 months; P<.001) and median overall survival (11.1 vs 6.8 months; P<.001) compared to gemcitabine alone 1. Therefore, FOLFIRINOX should be considered the standard of care for patients with pancreatic cancer and good performance status (ECOG 0-1).
From the Research
Folfirinox Overview
- FOLFIRINOX is a combination chemotherapy regimen used to treat metastatic pancreatic cancer, consisting of 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin 2.
- The introduction of FOLFIRINOX and gemcitabine plus nab-paclitaxel therapy has significantly improved overall treatment outcomes for metastatic pancreatic cancer patients 2.
Efficacy and Survival
- A retrospective multicentric analysis found that the median progression-free survival (PFS) and overall survival (OS) for patients treated with FOLFIRINOX as first-line therapy were 5.97 months and 8.93 months, respectively 3.
- The use of granulocyte colony-stimulating factor was identified as a good prognostic factor, while dose intensity of oxaliplatin and bolus of fluorouracil appeared as pejorative factors 3.
- A study evaluating the efficacy of FOLFIRINOX in metastatic or recurrent pancreatic cancer found a 6-month progression-free survival rate of 59.3% and an overall response rate of 10% 4.
Comparison with Other Treatments
- A comparison of nanoliposomal irinotecan plus fluorouracil and leucovorin (5-FU/LV) and modified FOLFIRINOX (mFFX) as second-line treatment after gemcitabine with nab-paclitaxel found no significant difference in efficacy between the two groups 5.
- The study suggested that nanoliposomal irinotecan plus 5-FU/LV may be a viable alternative to mFFX as second-line treatment after gemcitabine with nab-paclitaxel 5.
Toxicity and Adverse Events
- FOLFIRINOX is associated with severe toxicity, including neutropenia, leucopenia, and thrombocytopenia, as well as non-hematological toxicities such as diarrhea, nausea, and vomiting 4.
- A study found that anorexia, fatigue, and peripheral neuropathy were more common in the modified FOLFIRINOX group, but there was no difference in grade 3/4 adverse events between the two groups 5.