What FOLFIRI is
The name combines FOL (folinic acid or leucovorin), F (5-fluorouracil, 5-FU) and IRI (irinotecan). Irinotecan blocks an enzyme (topoisomerase I) that cells need to copy their DNA. In metastatic colorectal cancer FOLFIRI and FOLFOX are equally effective; the order in which they are used depends on which side effects you want to avoid and on what you have already received. It is common to start with one and switch to the other when the first stops working.
It is usually combined with a biological drug: bevacizumab or aflibercept (anti-angiogenic drugs) or, if the tumour is RAS wild-type, cetuximab or panitumumab. The intensive version with three chemotherapy drugs, FOLFOXIRI, is reserved for people in good general health when the aim is to shrink the tumour as much as possible (for example, to try to operate on metastases).
How it is given
Each cycle lasts 14 days. On day 1, at the day unit: irinotecan over about 90 minutes, leucovorin and a bolus of 5-FU; then you are connected to the portable pump with 5-FU for 46 hours, through the port-a-cath or PICC line. The number of cycles is not fixed in advance: treatment continues while it works and is tolerated, with a CT scan every 2-3 months.
Before starting: DPD and UGT1A1
- DPD (DPYD gene): the test done before any treatment with 5-FU or capecitabine. If the enzyme is lacking, 5-FU can be very toxic. Ask whether you have had it.
- UGT1A1: the enzyme that clears irinotecan. People with the UGT1A1*28 variant on both copies (the same one behind Gilbert's syndrome) have a higher risk of severe diarrhoea and neutropenia, and the dose is usually reduced. Not every hospital tests it routinely; if you have "always had" a raised bilirubin or a diagnosis of Gilbert's syndrome, tell your oncologist.
Diarrhoea: two different kinds
| Early diarrhoea | Late diarrhoea | |
|---|---|---|
| When | During the infusion or in the first 24 h | From day 3-5 onwards, may last several days |
| Why | "Cholinergic syndrome": also sweating, watery eyes, cramps, drooling | Direct damage to the bowel lining |
| What is done | Treated at the hospital with atropine; if it happens once, it is given preventively in later cycles | Loperamide from the first loose stool, following the intensive schedule your team gives you (different from the leaflet), a bland diet and plenty of fluids |
Late diarrhoea is the effect that causes most trouble with irinotecan. Do not wait "to see if it passes": start loperamide as soon as it appears. Call or go to the emergency department if it lasts more than 24 hours despite medication, if there is fever or blood, if you feel dizzy when standing up, or if you cannot drink. Diarrhoea combined with low white cells is dangerous and is treated in hospital.
Other common effects
- Hair loss: unlike FOLFOX, it is common with irinotecan (complete or partial). Hair grows back after treatment. Ask about scalp cooling if it is offered and about wig subsidies in your region.
- Low white cells (neutropenia): not noticeable unless there is an infection. Blood test before each cycle. Fever of 38 °C or more = emergency department, without waiting.
- Nausea and vomiting: well controlled with the prescribed medication; take it even if you feel fine during the first days.
- Tiredness, mouth sores, loss of appetite.
- It does not cause the neuropathy or cold sensitivity of oxaliplatin; that is why FOLFIRI is the alternative when that neuropathy makes it impossible to continue FOLFOX.
When to call or go to the emergency department
- Fever of 38 °C or more, or chills.
- Diarrhoea that does not settle within 24 h on loperamide, with blood, or more than 6-8 stools a day.
- Vomiting that prevents you from drinking or taking your medication.
- Signs of dehydration: very dry mouth, very little dark urine, dizziness.
- Pain, redness or swelling in the arm or neck on the side of the line.
What to ask at your appointment
- Have I had the DPD test? And the UGT1A1 test?
- What exactly is the loperamide schedule I should follow if I get diarrhoea?
- Which biological drug is it combined with in my case, and why?
- How often will a CT scan be done to check whether it is working?
- Which number do I call if I have fever or diarrhoea at the weekend?
