FOLFIRI Chemotherapy
FOLFIRI combines folinic acid, fluorouracil and irinotecan every two weeks, with a portable pump for 46 hours. It is one of the two backbone regimens for metastatic bowel cancer, matched FOLFOX for survival in the GERCOR trial, and with cetuximab reached a median of 28.7 months in FIRE-3.
About This Department
Three drugs, every two weeks, with a small pump that goes home with you. FOLFIRI is one of the two backbones of bowel cancer treatment.
A treatment plan for bowel cancer that has spread, or that has come back, names FOLFIRI, sometimes with cetuximab, panitumumab or bevacizumab after it. Its name abbreviates its three drugs. Folinic acid, fluorouracil and irinotecan are given on one day every two weeks, and the fluorouracil keeps running for 46 hours from a small pump carried home in a bag. In the French GERCOR trial, first-line FOLFIRI shrank the cancer in 56 percent of patients. Starting with FOLFIRI or with its partner regimen FOLFOX made no difference to survival, which was 21.5 and 20.6 months, so the choice turns on side effects and on what comes next. Adding cetuximab in cancers without a RAS mutation took median survival to 28.7 months in the German FIRE-3 trial. This page explains how a cycle runs, which cancers it treats, the two gene tests that make it safer, how to handle its main side effect, and how a treatment given every two weeks fits with a visit to Istanbul.
What the name means
FOLFIRI Chemotherapy combines three drugs, and the name comes from their initials.
FOL, folinic acid
F, fluorouracil
IRI, irinotecan
FOLFIRI and FOLFOX differ by one drug. FOLFOX uses oxaliplatin in place of irinotecan. The two work equally well in trials, and most patients with advanced bowel cancer receive one and then the other.
The two-week cycle
A cycle takes fourteen days, and only the first three involve any treatment. Day 1 happens in the oncology day unit. Days 2 and 3 happen at home with the pump.
| When | What | How long |
|---|---|---|
| Day 1, morning | Blood tests and a visit with the oncologist, who checks the count and asks about the last cycle | One to two hours |
| Day 1 | Anti-sickness medicine, then irinotecan and folinic acid into the vein, run side by side | Ninety minutes to two hours |
| Day 1 | A short push of fluorouracil | A few minutes |
| Day 1 to day 3 | Fluorouracil by continuous infusion from a portable pump | 46 hours, at home |
| Day 3 | The pump is disconnected at the clinic, or at home by a nurse | Fifteen minutes |
| Days 4 to 14 | Recovery. The next cycle starts on day 15 | Eleven days |
Twelve cycles make six months. For advanced disease nobody fixes the count in advance, and treatment continues while it works and is tolerated, often with breaks or a lighter maintenance schedule once the cancer is under control.
The port and the pump
Most patients receiving FOLFIRI have a port, a small chamber placed under the skin of the upper chest with a thin tube running into a large vein. It spares the arm veins, which fluorouracil irritates over months, and makes every cycle a single needle into the port.
- Placing the port. A short procedure under local anesthetic, done once before the first cycle or on the same day.
- Connecting the pump. A balloon or electronic pump the size of a water bottle is attached to the port needle at the end of day 1, and it rides in a small bag or a belt pouch.
- Two days at home. Showering is done with the pump and the needle covered. Sleeping is normal. The pump empties itself.
- Disconnecting. On day 3 the needle comes out and the port is flushed. Nothing shows under the skin between cycles except a small bump.
Which cancers
Bowel cancer accounts for most FOLFIRI treatment. Elsewhere in the digestive tract it serves as a later option, after the first regimen has stopped working and the patient remains well enough for three drugs.
| Cancer | When | Usually combined with |
|---|---|---|
| Bowel cancer, metastatic | First line, as an alternative to FOLFOX | Cetuximab or panitumumab if RAS wild-type and left-sided, bevacizumab otherwise |
| Bowel cancer, metastatic | Second line, after FOLFOX has stopped working | Bevacizumab, aflibercept or ramucirumab, or an anti-EGFR antibody if not used before |
| Bowel cancer, liver metastases that might become removable | To shrink them before surgery | An antibody chosen by RAS status |
| Stomach and esophageal cancer | Second or later line | Ramucirumab in some regimens |
| Pancreatic cancer | After gemcitabine, in some centers | Alone |
After surgery for early bowel cancer, FOLFIRI has no place. Trials showed irinotecan added nothing there. FOLFOX or capecitabine with oxaliplatin is the standard for that setting.
FOLFIRI or FOLFOX first
The GERCOR trial, published in the Journal of Clinical Oncology in 2004, gave 220 patients with untreated metastatic bowel cancer either FOLFIRI followed by FOLFOX, or the reverse, and found four things.
- Survival was the same. 21.5 months starting with FOLFIRI, 20.6 months starting with FOLFOX.
- First-line results were the same. Tumor shrinkage in 56 against 54 percent, and 8.5 against 8.0 months before the cancer grew.
- Second-line results favored FOLFOX slightly. Given after FOLFIRI, FOLFOX shrank tumors in 15 percent. FOLFIRI given after FOLFOX, in 4 percent.
- The side effects differed. FOLFIRI caused more mouth sores, nausea, vomiting and hair loss. FOLFOX caused more low white cell counts and nerve damage.
Adding an antibody
A targeted antibody joins FOLFIRI in nearly every plan, and the gene tests on the tumor decide which.
Two gene tests before the first dose
Two of these tests look at the patient and one at the tumor. Together they decide the dose, and sometimes the whole plan.
| Test | What it finds | What changes |
|---|---|---|
| DPD deficiency, DPYD gene | A shortfall in the enzyme that breaks down fluorouracil. Present in a few percent of people | The fluorouracil dose is reduced, or the drug avoided, since a normal dose can be fatal |
| UGT1A1*28 | A slow version of the enzyme that clears irinotecan, common in people with Gilbert syndrome | The irinotecan dose starts lower, because diarrhea and low white counts are more severe |
| Microsatellite instability, MSI or dMMR | A tumor with faulty DNA repair, in about 5 percent of metastatic bowel cancers | Immunotherapy replaces chemotherapy as the first treatment, with far better results |
Two blood tests about the patient, one test on the tumor. All three should be in the file before the first FOLFIRI cycle, and the review checks that they are.
Diarrhea, the side effect to know
Irinotecan causes diarrhea in two distinct ways, at two different times, and each has its own treatment. Telling them apart keeps a manageable problem from turning dangerous.
| Early | Late | |
|---|---|---|
| When | During or within 24 hours of the infusion | From the second day onward, peaking around day 5 to 7 |
| With it | Sweating, cramps, watery eyes, a runny nose, slow pulse | Watery stools, sometimes many a day |
| Cause | A reaction of the nerves of the gut to irinotecan | Direct damage to the bowel lining |
| Treatment | An injection of atropine, given in the day unit, and before later cycles as prevention | Loperamide at home, by the rule below, and hospital fluids if it does not settle |
The loperamide rule
At the first loose stool after day 1, take two loperamide capsules. Then one every two hours, two every four hours at night, until twelve hours have passed with no loose stool. Drink at least two liters a day. If diarrhea lasts more than 24 hours on this plan, or comes with fever, dizziness or blood, go to hospital the same day, because irinotecan diarrhea with a low white count is an emergency.
Other side effects
The remaining effects will sound familiar from other chemotherapy, and most prove milder than patients fear.
| Effect | How common | What helps |
|---|---|---|
| Low white cell count | Common, lowest around days 7 to 10 | A blood count before each cycle. Growth factor injections when it keeps falling |
| Nausea and vomiting | Common in the first days | Two or three anti-sickness drugs before each cycle |
| Hair thinning or loss | Common with irinotecan | Grows back after treatment |
| Mouth sores | Frequent with fluorouracil | Mouthwash, soft food, and a lower dose if severe |
| Tiredness | Builds over months | Rest, activity, and treatment breaks |
| Hand-foot soreness | Sometimes, from fluorouracil | Moisturizer, and a dose change if it blisters |
Fever above 38 degrees in the ten days after a cycle means the emergency department, the same day. A low white count can turn an ordinary infection into a serious one within hours.
Days in Istanbul
First cycle
Two cycles here
Later cycles
What a quote contains
No figure appears on this page. A quote you can compare names the antibody, the dose by body surface area or weight, the number of cycles, whether the port and the pump are included, and whether the gene tests are inside the figure. Packages published by Turkish hospitals and medical travel agencies for chemotherapy cover consultation, a stated number of cycles and the day unit, and leave out later cycles, scans, flights and accommodation. The quote follows the free review.
Coordinator, language, companion
A companion is worth bringing for the first cycle. The office books accommodation near the hospital, arranges airport transfers and the car for the pump days, and issues an appointment confirmation and invitation letter for a visa ten days or so before travel. The kitchen prepares halal, vegetarian and diabetic meals, a prayer room is on site, and a female physician is arranged where the rota allows for anyone who asks in the first message.
Cycles at home
What your oncologist receives
Once you get back home, your oncologist receives the protocol with every dose, the gene test results and any dose reductions they led to, the antibody plan, the loperamide and fever rules in writing, and the schedule below.
| Check | How often |
|---|---|
| Blood count, kidney and liver tests | Before every cycle |
| Blood pressure and urine protein, on bevacizumab | Before every cycle |
| Magnesium, on cetuximab or panitumumab | Every few cycles |
| CT of chest, abdomen and pelvis | Every two to three months |
| CEA tumor marker | Every cycle or every other |
Every scan and CEA result goes to the coordinator. The oncologist here reviews it at no charge and says whether to continue, pause, change the antibody, or ask a liver surgeon whether the metastases can now be removed.
FOLFIRI Chemotherapy FAQ
What does FOLFIRI stand for?
Is FOLFIRI better than FOLFOX?
How long does FOLFIRI treatment last?
What is the worst side effect of FOLFIRI?
Is FOLFIRI given with cetuximab?
How long do I need to stay in Istanbul?
Will the staff be able to speak my language?
References
- Tournigand C, André T, Achille E, et al. FOLFIRI followed by FOLFOX6 or the reverse sequence in advanced colorectal cancer: a randomized GERCOR study. Journal of Clinical Oncology. 2004;22(2):229-237.
- Van Cutsem E, Köhne CH, Hitre E, et al. Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. The New England Journal of Medicine. 2009;360(14):1408-1417.
- Heinemann V, von Weikersthal LF, Decker T, et al. FOLFIRI plus cetuximab versus FOLFIRI plus bevacizumab as first-line treatment for patients with metastatic colorectal cancer (FIRE-3): a randomised, open-label, phase 3 trial. The Lancet Oncology. 2014;15(10):1065-1075.
Editor's note
Written by the Biruni Hospital medical editorial team. Reviewed by Prof. Dr. Mustafa Teoman YANMAZ, Medical Oncology.
Medically reviewed by
Prof. Dr. Mustafa Teoman YANMAZ
Medical Oncology
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