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FOLFIRINOX

oxaliplatin + irinotecan + leucovorin + fluorouracil (5-FU)
Cytotoxic Combination Chemotherapy Combination Regimen

FOLFIRINOX is a multi-agent chemotherapy regimen combining oxaliplatin, irinotecan, leucovorin, and fluorouracil (5-FU). It is a standard first-line regimen for metastatic pancreatic cancer and is also used in colorectal cancer.

Indications and Usage

Metastatic pancreatic cancer (first-line): Patients with good performance status (ECOG 0–1). Colorectal cancer: Used as FOLFIRINOX or modified mFOLFIRINOX in metastatic and adjuvant settings. Gastric/GEJ cancer: Investigational in some settings.

Dosing and Administration

FOLFIRINOX (standard, every 2 weeks):
Day 1: Oxaliplatin 85 mg/m² IV over 2 hours, then leucovorin 400 mg/m² IV over 2 hours (concurrently with irinotecan), then irinotecan 180 mg/m² IV over 90 minutes, then 5-FU 400 mg/m² IV bolus, then 5-FU 2400 mg/m² continuous IV infusion over 46–48 hours.
Modified mFOLFIRINOX: Irinotecan 150 mg/m², oxaliplatin 85 mg/m², leucovorin 400 mg/m², 5-FU 2400 mg/m² CI (no bolus 5-FU) — may have improved tolerability.

Warnings and Precautions
  • Myelosuppression: Neutropenia is the dose-limiting toxicity. Monitor CBC before each cycle. Prophylactic G-CSF recommended.
  • Severe Diarrhea: Irinotecan-related early (cholinergic) and delayed diarrhea. Delayed diarrhea requires prompt loperamide therapy; severe cases require IV fluids.
  • Nausea/Vomiting: Highly emetogenic. Requires multi-agent antiemetic prophylaxis.
  • Peripheral Neuropathy: Cumulative, dose-dependent oxaliplatin-related sensory neuropathy.
  • Hepatotoxicity: Oxaliplatin-associated sinusoidal obstruction syndrome (SOS) with long-term use.
  • UGT1A1*28 Polymorphism: Patients homozygous for UGT1A1*28 are at increased risk for severe irinotecan toxicity. Consider dose reduction.
  • Embryo-Fetal Toxicity: All components are teratogenic. Effective contraception required.
Adverse Reactions
Common Adverse Reactions

Neutropenia (46%), Nausea (73%), Fatigue (76%), Diarrhea (45%), Vomiting (47%), Peripheral neuropathy (56%), Alopecia (11%), Thrombocytopenia (33%)

Neutropenia
46%
Nausea
73%
Fatigue
76%
Diarrhea
45%
Vomiting
47%
Peripheral neuropathy
56%
Alopecia
11%
Thrombocytopenia
33%

Adverse reaction frequencies reflect combination regimen data. Consult individual prescribing information for complete details.

Mechanism of Action

FOLFIRINOX combines four agents with distinct mechanisms: Oxaliplatin (DNA cross-linking, platinum compound), Irinotecan (topoisomerase I inhibition via active SN-38 metabolite), Leucovorin (enhances 5-FU binding to thymidylate synthase), and 5-Fluorouracil (thymidylate synthase inhibition and RNA incorporation). The combination achieves synergistic multi-pathway cytotoxicity.

Pivotal Clinical Studies
  • PRODIGE 4/ACCORD 11 — FOLFIRINOX vs gemcitabine in metastatic pancreatic cancer. Phase III, n=342. FOLFIRINOX significantly improved OS (11.1 vs 6.8 months, HR 0.57).
  • ACCORD 18/UNICANCER PRODIGE 7 — FOLFIRINOX in resectable/borderline resectable pancreatic cancer. Phase II/III.
Additional Resources
Approved Tumor Types
External Resources
Important Notice: This page is a clinical reference summary for the FOLFIRINOX regimen. It does not replace the full prescribing information for individual agents. Healthcare professionals should consult each drug's complete package insert before making prescribing decisions.