FOLFIRINOX Chemotherapy Day by Day

This page is for people about to start FOLFIRINOX chemotherapy, and the people helping them. It walks through one two-week cycle, day by day, and explains which side effects need a call.

FOLFIRINOX is not one drug. It is four, and the name is built from their initials:

• FOL is folinic acid, also called leucovorin. It is not a chemo drug. It is a vitamin-like helper that locks fluorouracil onto its target enzyme so the chemo works harder.
• F is fluorouracil, usually written 5-FU. It jams the enzyme cells use to make thymidine, one of the DNA building blocks.
• IRIN is irinotecan. It blocks topoisomerase I, an enzyme that untangles DNA during copying. Without it, the strands break.
• OX is oxaliplatin. It is a platinum drug that cross-links DNA so it cannot be read.

The regimen was built for pancreatic adenocarcinoma and is also used in some other gut cancers. It is demanding. The trial that put it on the map only enrolled people with an ECOG performance status of 0 or 1, meaning fully active or limited only in heavy work.

One cycle is 14 days, not 21. Day 1 is the long day.

Before anything runs, you get anti-nausea medicine. Irinotecan can trigger a cholinergic reaction during the infusion. That means cramping, sweating, watery eyes, runny nose, or sudden diarrhea. So teams often give atropine, by vein or as a small injection under the skin. They give it either up front or the moment symptoms start. The nurse draws up the amount.

The drugs in the original regimen studied in metastatic disease were:

• Oxaliplatin, infused over about 2 hours
• Irinotecan
• Leucovorin, which sharpens the effect of the 5-FU
• 5-FU, pushed quickly through the line
• 5-FU again, running continuously over the next 46 hours

The chemotherapy pharmacy works out every one of these from your height and weight. They are also trimmed for blood counts and side effects. So the amounts on your own treatment sheet will not match anybody else's.

Add access time, flushes, and the pump hookup, and day 1 can take most of the day. Ask your team how long to plan for. Many people get a port or a PICC line first, because the 46-hour infusion runs through a line that goes home with you.

The last 5-FU dose does not finish at the clinic. You leave wearing a small pump, often a balloon-type elastomeric pump in a pouch, that pushes 5-FU slowly for 46 hours. You shower with the site covered, you sleep with it, and you come back on day 3 to have it disconnected.

Know two things before you walk out. First, where the clamp is and what to do if the tubing leaks or the line pulls. Second, the phone number for the on-call service, not just the daytime clinic.

White blood cell counts drop in the days after treatment. Ask your team when your counts are expected to be lowest. In the metastatic trial, 5.4 percent of people on FOLFIRINOX developed febrile neutropenia, meaning fever with a dangerously low neutrophil count. Many teams add pegfilgrastim or filgrastim, growth-factor shots that push the marrow to make neutrophils faster. In the adjuvant PRODIGE-24 trial, 62.2 percent of people on the regimen needed growth factor.

Tiredness often comes and goes across the cycle. Ask your team what pattern to expect, and tell them if it stops you doing daily tasks.

Irinotecan causes diarrhea in two distinct patterns, and the label treats them separately.

Early diarrhea starts during or shortly after the infusion. It is the cholinergic reaction. It is usually short-lived and responds to atropine.

Late diarrhea starts more than 24 hours after the dose and can be life threatening. The label wants loperamide (Imodium) in your house before day 1, not fetched afterward. The regimen it gives is 4 mg at the first loose stool, then 2 mg every 2 hours until you have gone 12 hours with no diarrhea. Overnight, the label allows 4 mg every 4 hours. The label says these high doses should not run past 48 hours straight, because of the risk of paralytic ileus, a stalled bowel.

Go by the loperamide instructions your own team wrote for you, not by the figures above. They are the label's reference regimen. They are printed here so you can see why the tablets need to be in the cupboard before day 1, and why the first loose stool is the moment to start.

If diarrhea comes with fever or a very low neutrophil count, the label calls for antibiotics, not just anti-diarrheals. That is a hospital decision, so call.

Irinotecan is cleared by an enzyme called UGT1A1. Some people carry gene variants that make less of it. The label names UGT1A1*28/*28, *6/*6, and *6/*28 as genotypes with a higher risk of severe neutropenia. A blood test can check this. Ask whether your center tests before cycle 1, because a positive result can mean a lower starting irinotecan dose.

Oxaliplatin causes an unusual acute nerve effect. Cold triggers pins and needles, numbness, or an odd tight feeling in the hands, feet, around the mouth, or in the throat. Some people get a frightening sensation of throat tightness after a cold drink, without any real wheeze or stridor.

The oxaliplatin label says these effects start within hours to 2 days after a dose and usually clear within 14 days. The label says to avoid cold drinks, ice, and cold on the skin. In practice: no ice in drinks, no ice cubes, no cold drinks straight from the fridge, gloves for the freezer aisle, and warm water for washing. The effect fades between cycles at first. Over many cycles a longer-lasting numbness can build up. If it does, the label lets your team lower the oxaliplatin dose or stop it.

In metastatic pancreatic cancer, FOLFIRINOX gave a median overall survival of 11.1 months compared with 6.8 months for gemcitabine alone, and median progression-free survival of 6.4 versus 3.3 months.

After surgery, PRODIGE-24 compared 12 cycles of a modified FOLFIRINOX against six cycles of gemcitabine. The modified version uses the same four drugs, with a lower irinotecan amount and no rapid 5-FU push. Median overall survival was 53.5 months versus 35.5, and 5-year survival was 43.2 percent versus 31.4 percent. The cost was real. Grade 3 or 4 side effects hit 75.9 percent on FOLFIRINOX versus 52.9 percent on gemcitabine, and 33 percent stopped early.

• Call 911 or go to an emergency department if throat tightness or trouble swallowing does not ease within a few minutes, or you cannot catch your breath. Do not drive yourself.
• Call your oncology team straight away, day or night, if your temperature is 100.4°F (38°C) or higher while you are on treatment, or you have shaking chills. If they cannot be reached fast, go to an emergency department and tell them you are on FOLFIRINOX. Do not leave it until the clinic opens. Febrile neutropenia is the reason this regimen comes with growth-factor shots, and for CDC, a fever during chemotherapy counts as a medical emergency.
• Call your care team right away if you have diarrhea for the first time during treatment, diarrhea that does not stop within 24 hours, black or bloody stools, or nausea and vomiting so bad you cannot drink. MedlinePlus and the irinotecan label list all of these.
• Call your care team right away if you feel lightheaded, dizzy or faint. These can be signs of dehydration.
• Call your care team the same day if the pump alarms, leaks, or the line works loose.

Chemotherapy, How Chemotherapy Is Given, Diarrhea During Cancer Treatment, Fever During Chemo, and Low White Blood Cells During Chemotherapy.

• https://www.cancer.gov/types/pancreatic/hp/pancreatic-treatment-pdq
• https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=e518dfc6-7e93-4fee-a66c-51e1ab71c056
• https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=7dc8dfb1-dec8-43b3-b2ea-05eac054b2c6
• https://www.cdc.gov/cancer-preventing-infections/patients/fever.html
• https://medlineplus.gov/druginfo/meds/a608043.html