Advanced or Metastatic Pancreatic Cancer Regimen: Oxaliplatin + Irinotecan + Fluorouracil + Leucovorin (FOLFIRINOX)
Conroy T et al. N Engl J Med 2011;364:1817–1825
Oxaliplatin 85 mg/m2 intravenously in 250 mL 5% dextrose injection (D5W) over 2 hours on day 1, every 2 weeks (total dosage/cycle = 85 mg/m2)
Note: Oxaliplatin must not be mixed with sodium chloride injection
Either: (racemic) Leucovorin calcium 400 mg/m2 or levoleucovorin calcium 200 mg/m2 intravenously in 25–500 mL D5W or 0.9% sodium chloride injection over 2 hours on day 1, every 2 weeks (total dosage/cycle for racemic leucovorin = 400 mg/m2, for levoleucovorin = 200 mg/m2), followed 30 minutes after administration begins by:
Irinotecan 180 mg/m2 intravenously over 90 minutes in 500 mL D5W on day 1, 30 minutes after leucovorin (or levoleucovorin) administration begins, every 2 weeks (total dosage/cycle = 180 mg/m2), followed by:
(bolus) Fluorouracil 400 mg/m2 by intravenous injection over 1–2 minutes after leucovorin (or levoleucovorin) and irinotecan administration are completed on day 1, every 2 weeks, followed by:
Fluorouracil 2400 mg/m2 by continuous intravenous infusion over 46 hours in 100–1000 mL 0.9% NS or D5W, starting on day 1 every 2 weeks (total dosage/cycle = 2800 mg/m2)
Important note: This regimen is difficult for patients. Thus, FOLFIRINOX is a first-line option for patients with metastatic pancreatic cancer who are younger than 76 years and who have a good performance status (ECOG 0 or 1), no cardiac ischemia, and normal or nearly normal bilirubin levels
Notes:
Patients must be instructed in the use of loperamide as treatment for diarrhea, and must have a supply of this drug upon starting FOLFIRINOX
Filgrastim is not recommended as primary prophylaxis, but it could be considered for high-risk patients
The dose of leucovorin is not modified for toxicity, but is omitted if fluorouracil is omitted. Once a fluorouracil dose is decreased, it is not re-escalated
Supportive Care Antiemetic prophylaxis
Emetogenic potential is MODERATE
See Chapter 39 for antiemetic recommendations
Hematopoietic growth factor (CSF) prophylaxis
Primary prophylaxis may be indicated
See Chapter 43 for more information
Antimicrobial prophylaxis
Risk of fever and neutropenia is LOW
Antimicrobial primary prophylaxis to be considered:
See Chapter 47 for more information
Acute cholinergic syndrome
Atropine sulfate 0.25–1 mg subcutaneously or intravenously if abdominal cramping or diarrhea develop during or within 1 hour after irinotecan administration
If symptoms are severe, add as primary prophylaxis at least 30 minutes before irinotecan during subsequent cycles
For irinotecan, acute cholinergic syndrome may be characterized by: abdominal cramping, diarrhea, diaphoresis, hypotension, flushing, bradycardia, rhinitis, increased salivation, meiosis, and lacrimation
Diarrhea management
Latent or delayed onset diarrhea✫:
Loperamide 4 mg orally initially after the first loose or liquid stool, then
Loperamide 2 mg orally every 2 hours during waking hours, plus
Loperamide 4 mg orally every 4 hours during hours of sleep
Continue for at least 12 hours after diarrhea resolves
Recurrent diarrhea after a 12-hour diarrhea-free interval is treated as a new episode
Rehydrate orally with fluids and electrolytes during a diarrheal episode
If a patient develops blood or mucus in stool, dehydration, or hemodynamic instability, or if diarrhea persists >48 hours despite loperamide, stop loperamide and hospitalize the patient for IV hydration
Alternatively, a trial of Diphenoxylate hydrochloride 2.5 mg with Atropine sulfate 0.025 mg (eg, Lomotil)
Initial adult dose is 2 tablets 4 times daily until control has been achieved, after which the dose may be reduced to meet individual requirements. Control may often be maintained with as little as 2 tablets daily
Clinical improvement of acute diarrhea is usually observed within 48 hours. If improvement of chronic diarrhea after treatment with a maximum daily dose of 8 tablets is not observed within 10 days, control is unlikely with further administration
Persistent diarrhea:
Octreotide 100–150 mcg subcutaneously 3 times daily. Maximum total daily dose is 1500 mcg
Antibiotic therapy during latent or delayed onset diarrhea:
A fluoroquinolone (eg, Ciprofloxacin 500 mg orally every 12 hours) if absolute neutrophil count <500/mm3 with or without accompanying fever in association with diarrhea
Patient Population Studied