Modified FOLFIRINOX (m-FOLFIRINOX) Dosing and Schedule
The recommended modified FOLFIRINOX regimen eliminates the 5-FU bolus from the original protocol, using oxaliplatin 85 mg/m² IV, irinotecan 180 mg/m² IV, leucovorin 400 mg/m² IV on day 1, followed by 5-FU 2400 mg/m² as a 46-hour continuous infusion, repeated every 2 weeks. 1
Standard Dosing Components
The modified regimen differs critically from the original FOLFIRINOX by removing the 400 mg/m² 5-FU bolus, which significantly reduces toxicity while maintaining efficacy 1. The specific dosing is:
- Oxaliplatin: 85 mg/m² IV over 2 hours on day 1 2, 1
- Irinotecan: 180 mg/m² IV over 30-90 minutes on day 1 2, 1
- Leucovorin: 400 mg/m² IV over 2 hours on day 1 (equivalent to 200 mg/m² levoleucovorin) 2, 1
- 5-Fluorouracil: 2400 mg/m² as a 46-hour continuous infusion starting day 1 (NO bolus dose) 1
- Cycle frequency: Every 2 weeks 2, 1
Rationale for Modification
The elimination of the 5-FU bolus substantially improves the safety profile without compromising efficacy 1. In the modified regimen, grade 4 neutropenia occurred in only 3% of patients compared to higher rates with full-dose FOLFIRINOX, while grade 3/4 diarrhea and fatigue were each 13% 1. The original FOLFIRINOX showed 5.4% febrile neutropenia rates with the bolus included 2.
Alternative Dose-Reduced Schedules
For patients requiring further dose reduction, particularly in the second-line setting after gemcitabine failure, a more conservative approach uses:
- Oxaliplatin: 85 mg/m² IV on day 1 3
- Irinotecan: 100-125 mg/m² IV on day 1 (reduced from 180 mg/m²) 3
- Leucovorin: 400 mg/m² IV on day 1 3
- 5-FU: 400 mg/m² bolus followed by 2400 mg/m² continuous infusion 3
This dose level (irinotecan 100-125 mg/m²) was identified as the maximum tolerated dose in second-line therapy, with level 125 mg/m² chosen to maintain better compliance with the biweekly schedule 3.
Critical Safety Considerations
Always prescribe 5-FU as 1200 mg/m²/day for 2 days, NOT as 2400 mg/m² over 46 hours, to minimize medication errors 4, 5. This is a critical safety measure emphasized by NCCN guidelines 4.
Never confuse leucovorin 400 mg/m² with levoleucovorin 200 mg/m²—the active L-isomer requires exactly half the dose 5, 6, 7. Using the wrong formulation at the wrong dose can lead to either underdosing or excessive toxicity.
Monitor complete blood counts, liver function, renal function, and peripheral neuropathy before each cycle 5. Consider discontinuing oxaliplatin after 3-4 months if grade ≥2 neurotoxicity develops while continuing the fluoropyrimidine component 5.
Hematopoietic Growth Factor Support
The use of prophylactic granulocyte colony-stimulating factor (G-CSF) is recommended with modified FOLFIRINOX to further reduce neutropenia risk 1. This addition, combined with bolus 5-FU elimination, creates the optimal risk-benefit profile.
Patient Selection Criteria
Modified FOLFIRINOX is appropriate for patients with ECOG performance status 0-1 2. The original FOLFIRINOX trial excluded patients with performance status ≥2, and this restriction should be maintained even with the modified regimen 2. The regimen shows particular promise in both metastatic disease (median overall survival 9.0 months) and nonmetastatic locally advanced or borderline resectable disease (median overall survival 17.8 months) 1.