Standard Biweekly FOLFIRI Dosing Regimen
The standard biweekly FOLFIRI regimen consists of irinotecan 180 mg/m² IV over 30-90 minutes on day 1, leucovorin 400 mg/m² IV over 2 hours on day 1,5-FU 400 mg/m² IV bolus on day 1, followed by 5-FU 1200 mg/m²/day continuous infusion over 2 days (total 2400 mg/m² over 46-48 hours), repeated every 2 weeks. 1, 2, 3
Detailed Dosing Components
Irinotecan
- Dose: 180 mg/m² IV
- Infusion time: 30-90 minutes (flexibility in infusion duration)
- Day: Day 1 only
Leucovorin (Folinic Acid)
- Dose: 400 mg/m² IV (or levoleucovorin 200 mg/m², which is equivalent)
- Infusion time: 2 hours, matched to duration of irinotecan infusion
- Day: Day 1 only
- Note: The 400 mg/m² leucovorin dose is equivalent to 200 mg/m² levoleucovorin 1, 2
5-Fluorouracil (5-FU)
- Bolus dose: 400 mg/m² IV bolus on day 1
- Continuous infusion: 1200 mg/m²/day × 2 days (total 2400 mg/m² over 46-48 hours)
- Critical safety note: NCCN recommends limiting chemotherapy orders to 24-hour units (i.e., 1200 mg/m²/day NOT 2400 mg/m² over 48 hours) to minimize medication errors 1, 2
Cycle Frequency
- Repeat every 2 weeks (14 days)
Modified FOLFIRI Regimen (Alternative)
An older two-day version exists but is less commonly used:
- Irinotecan 180 mg/m² IV day 1
- Leucovorin 200 mg/m² IV days 1 and 2
- 5-FU 400 mg/m² IV bolus followed by 600 mg/m² over 22 hours on days 1 and 2
- Repeated every 2 weeks 1
Important Clinical Considerations
UGT1A1 Testing
Patients with UGT1A1 polymorphisms (*28/*28, *6/*6, *6/*28) are poor metabolizers at increased risk for severe neutropenia due to elevated SN-38 exposure. Consider dose reduction in these patients, particularly when using irinotecan doses >125 mg/m² 4.
Infusional 5-FU Preference
Infusional 5-FU is strongly preferred over bolus regimens when combining with irinotecan. Bolus-only 5-FU regimens are inappropriate as combination regimens with irinotecan 1.
Combination with Biologics
When adding bevacizumab: 5 mg/kg IV on day 1, repeated every 2 weeks 2, 5
When adding cetuximab (RAS wild-type only): Either 400 mg/m² first infusion then 250 mg/m² weekly, OR 500 mg/m² every 2 weeks 2
Common Pitfalls to Avoid
- Medication error risk: Always order 5-FU as 1200 mg/m²/day for 2 days, NOT as 2400 mg/m² over 48 hours to prevent dosing errors
- Port requirement: This regimen requires central venous access for the 46-48 hour continuous infusion
- Leucovorin vs levoleucovorin confusion: Remember that 400 mg/m² leucovorin = 200 mg/m² levoleucovorin
- Irinotecan timing: Administer irinotecan before the 5-FU infusion begins