FOLFOX Dosing for Periampullary Carcinoma
For periampullary carcinoma, use the standard FOLFOX4 regimen: oxaliplatin 85 mg/m² IV on day 1, leucovorin 200-400 mg/m² IV on days 1-2,5-FU 400 mg/m² IV bolus followed by 600 mg/m² as 22-hour continuous infusion on days 1-2, repeated every 2 weeks. 1
Evidence Basis
The ABC-06 trial specifically evaluated FOLFOX in advanced biliary tract cancers, which includes ampullary carcinoma, demonstrating significant survival benefit in the second-line setting 1. This represents the highest-quality evidence directly addressing periampullary malignancies with FOLFOX chemotherapy.
Standard FOLFOX4 Dosing Schedule
The recommended dosing regimen consists of 2:
- Oxaliplatin: 85 mg/m² IV over 2 hours on day 1
- Leucovorin: 200 mg/m² IV over 2 hours on days 1 and 2 (or 400 mg/m² if using racemic leucovorin instead of levoleucovorin) 2, 3
- 5-Fluorouracil: 400 mg/m² IV bolus, then 600 mg/m² as 22-hour continuous infusion on days 1 and 2
- Cycle frequency: Every 2 weeks 2
Alternative mFOLFOX6 Regimen
An acceptable alternative is mFOLFOX6, which simplifies administration 2:
- Oxaliplatin: 85 mg/m² IV on day 1
- Leucovorin: 400 mg/m² IV on day 1
- 5-Fluorouracil: 400 mg/m² IV bolus on day 1, then 2,400 mg/m² (1,200 mg/m²/day × 2 days) as 46-48 hour continuous infusion
- Cycle frequency: Every 2 weeks 2
Clinical Context for Periampullary Carcinoma
The ABC-06 trial enrolled patients with advanced biliary tract cancers including ampullary carcinoma who progressed on first-line cisplatin-gemcitabine 1. The study demonstrated:
- Median overall survival of 6.2 months with FOLFOX versus 5.3 months with active symptom control alone (HR 0.69, p=0.031) 1
- 6-month survival rate of 50.6% versus 35.5% 1
- 12-month survival rate of 25.9% versus 11.4% 1
Important Safety Considerations
Dose Modifications
Monitor complete blood counts, liver function, renal function, and peripheral neuropathy before each cycle 4. Consider discontinuing oxaliplatin after 3-4 months if grade ≥2 neurotoxicity develops while maintaining fluoropyrimidine 4.
Common Toxicities
Grade 3-4 adverse events in the ABC-06 trial included 1:
- Neutropenia: 12% of patients
- Fatigue/lethargy: 11% of patients
- Infection: 10% of patients
- Three chemotherapy-related deaths occurred (infection, acute kidney injury, febrile neutropenia)
Critical Dosing Safety
Never confuse leucovorin (400 mg/m²) with levoleucovorin (200 mg/m²)—the active isomer requires half the dose 2, 3. Limit chemotherapy orders to 24-hour units (prescribe as 1,200 mg/m²/day, NOT 2,400 mg/m²/day over 46 hours) to minimize medication errors 2, 3.
Treatment Duration and Monitoring
Administer FOLFOX for a maximum of 12 cycles or until disease progression, unacceptable toxicity, or patient refusal 1. Perform response evaluation after 2-3 months using CT scan with contrast 4. Monitor CEA levels if initially elevated 4.