FOLFIRINOX

1. FOLFIRINOX Overview

Type: Combination chemotherapy
Components:
1. FOL – Folinic acid (Leucovorin) → enhances 5-FU efficacy
2. F – 5-Fluorouracil (5-FU) → antimetabolite, pyrimidine analog
3. IRIN – Irinotecan → topoisomerase I inhibitor
4. OX – Oxaliplatin → platinum agent, causes DNA crosslinks
Primary Indication:
- Metastatic or locally advanced pancreatic adenocarcinoma
- Sometimes used in perioperative or adjuvant settings

Drug	Dose	Route	Notes
Oxaliplatin	85 mg/m²	IV over 2 h	Day 1
Leucovorin	400 mg/m²	IV over 2 h	Day 1, given with Oxaliplatin
Irinotecan	180 mg/m²	IV over 90 min	Day 1
5-FU	400 mg/m² IV bolus, then 2400 mg/m² continuous infusion over 46 h	IV	Day 1
Cycle	Every 2 weeks	–	Adjusted based on toxicity

Note: Many centers use modified FOLFIRINOX (mFOLFIRINOX): bolus 5-FU omitted to reduce myelosuppression and diarrhea.

Synergistic multi-target approach:
- 5-FU + Leucovorin: inhibits thymidylate synthase → blocks DNA synthesis
- Irinotecan: prevents DNA religation → DNA damage and apoptosis
- Oxaliplatin: forms DNA adducts → apoptosis
Combination exploits different phases of cell cycle → increased cytotoxicity

Drug	Main Toxicities	Monitoring / Management
Oxaliplatin	Peripheral neuropathy (acute cold-induced), myelosuppression	Neurologic assessment, CBC
Irinotecan	Diarrhea (early & late), neutropenia	Loperamide for diarrhea, CBC, hydration
5-FU	Mucositis, diarrhea, myelosuppression, hand-foot syndrome	CBC, hydration, supportive care
General	Myelosuppression, fatigue, infection risk	CBC before each cycle, dose adjustments for toxicity

Patient selection: Only fit patients (ECOG 0–1) due to high toxicity
Supportive care: Antiemetics (5-HT3 antagonists + dexamethasone), growth factors if needed
Renal/Hepatic adjustment:
- Irinotecan: caution if bilirubin elevated
- Oxaliplatin: dose adjustment if severe renal impairment
Combination therapy advantage: Significantly improves survival vs gemcitabine monotherapy in metastatic pancreatic cancer (median OS ~11 months vs ~6.8 months)

Summary Table (Quick Reference)

Regimen	Components	Indication	Route	Cycle
FOLFIRINOX	Oxaliplatin + Leucovorin + Irinotecan + 5-FU	Metastatic / locally advanced pancreatic adenocarcinoma	IV	q2w