Definition:
- FOLFIRI is a combination chemotherapy regimen used primarily in metastatic colorectal cancer.
- Components:
| Component | Mechanism | Route / Notes |
|---|---|---|
| FOL – Leucovorin (folinic acid) | Enhances 5-FU binding to thymidylate synthase → potentiates 5-FU cytotoxicity | IV, given concurrently with 5-FU |
| F – 5-Fluorouracil (5-FU) | Antimetabolite → inhibits thymidylate synthase → blocks DNA synthesis | IV bolus + continuous infusion |
| IRI – Irinotecan | Topoisomerase I inhibitor → prevents DNA replication → cell death | IV, dose based on BSA, may require premedication |
Typical Dosing Schedule (every 2 weeks)
- Irinotecan: 180 mg/m² IV over 90 min on day 1
- Leucovorin: 400 mg/m² IV over 2 hours on day 1 (concurrent with irinotecan)
- 5-FU: 400 mg/m² IV bolus on day 1 → then 2400–2600 mg/m² continuous IV infusion over 46–48 hours
Clinical Use
- Metastatic colorectal cancer (mCRC)
- Often used first-line or after oxaliplatin-based therapy (e.g., FOLFOX)
- Can be combined with targeted therapy based on molecular profile:
- Anti-VEGF: Bevacizumab
- Anti-EGFR: Cetuximab or Panitumumab (KRAS/NRAS wild-type only)
Key Toxicities
- Irinotecan: diarrhea (acute cholinergic and delayed), neutropenia, alopecia
- 5-FU: mucositis, diarrhea, myelosuppression, hand-foot syndrome
- Leucovorin: minimal toxicity, potentiates 5-FU effects
- Overall: risk of myelosuppression, GI toxicity; requires monitoring and supportive care
Pharmacist Considerations
- Pre-medication: anticholinergic (e.g., atropine) for acute irinotecan-induced diarrhea
- Delayed diarrhea: loperamide protocol education
- Myelosuppression monitoring: CBC prior to each cycle
- Drug interactions: irinotecan metabolized by CYP3A4 → interactions with strong inhibitors/inducers
- Dose adjustments: based on toxicity (neutropenia, diarrhea, liver function)
- Supportive care: hydration, antiemetics, growth factors if needed
Summary
FOLFIRI = 5-FU + Leucovorin + Irinotecan, a standard chemotherapy backbone for metastatic colorectal cancer, often combined with targeted therapies. Pharmacists monitor toxicity, support anti-diarrheal and myelosuppression management, and advise on drug interactions.