FOLFOX Chemotherapy
FOLFOX combines folinic acid, fluorouracil and oxaliplatin in a two-weekly cycle with a 46-hour home pump. After colon cancer surgery it raised five-year disease-free survival from 67.4 to 73.3 percent, and for lower-risk stage III disease three months now works as well as six, sparing half the nerve damage.
About This Department
Every two weeks, a two-hour drip and a small pump you carry home for two days. After colon cancer surgery, it lowers the chance of the cancer returning.
FOLFOX combines three drugs, folinic acid, fluorouracil and oxaliplatin, in a cycle that repeats every 14 days. Oncologists rely on it as the backbone of chemotherapy for bowel cancer after surgery and in advanced disease, and use it widely for stomach and esophageal cancer. In the MOSAIC trial of 2,246 patients after surgery for colon cancer, adding oxaliplatin raised five-year disease-free survival from 67.4 to 73.3 percent. For many lower-risk patients, three months of treatment now does the work that once took six.
FOL stands for folinic acid, F for fluorouracil and OX for oxaliplatin, and the regimen has been in use for a quarter of a century. This page explains the FOLFOX Chemotherapy schedule, the trials that made it standard, the choice between three and six months, what a cycle feels like, the numbness that the cold brings on, and how a patient from abroad can combine it with travel.
What FOLFOX is
Each drug has a job. Fluorouracil, known as 5-FU, blocks the building blocks of DNA in dividing cells, and folinic acid, a vitamin relative also called leucovorin, makes fluorouracil work harder and longer inside the tumor. Oxaliplatin binds DNA. Cells cannot copy it. Together they work better than any one of them alone, and the fluorouracil is given partly as a slow drip over 46 hours because the drug acts longer that way.
One cycle every 14 daysOxaliplatin and folinic acid run into a vein over two hours on day one, then a small dose of fluorouracil is pushed in and the rest is connected to a portable pump that delivers it over the next 46 hours at home or in the hotel.
FOLFOX4, mFOLFOX6 and the other versions
Where it is used
- Colon cancer after surgery, stage III and high-risk stage II, to lower the chance of return.
- Rectal cancer, as part of treatment before or after surgery with radiotherapy.
- Advanced bowel cancer, as first or second treatment, often with bevacizumab, cetuximab or panitumumab according to the tumor's genes.
- Stomach and esophageal adenocarcinoma, before and after surgery, and with nivolumab in advanced disease.
- Other cancers, such as some cancers of the pancreas, bile ducts and small bowel, mostly in variations of the regimen that add or swap a drug.
MSI-high bowel cancer is a different diseaseAbout one in seven bowel cancers carries a mismatch repair defect, called MSI-high. In stage II these rarely benefit from fluorouracil, and in advanced disease immunotherapy has replaced chemotherapy as the first treatment. Every pathology report should include this test.
After colon cancer surgery
The MOSAIC trial
Three months or six
Oxaliplatin numbness builds with every dose, so shorter treatment matters if it works as well.
The question looked simple and took six trials in twelve countries to answer. Doctors wanted to know whether half the course, three months instead of six, could protect patients just as well while sparing them half the nerve damage. The trials in Italy, the United Kingdom, France, Greece, Japan and North America were run separately and pooled from the start, which gave the analysis more patients than any single study could recruit. It depended on two things. First came the risk of the cancer, judged from the depth of the tumor and the number of involved lymph nodes. Second came the regimen itself, because the three-weekly CAPOX schedule, with oxaliplatin by drip and capecitabine tablets at home, performed better at three months than two-weekly FOLFOX did. Oncologists now sort patients into two groups before choosing the length. The conversation takes minutes. It saves many patients three months of treatment and a good deal of lasting numbness.
- Lower risk, T1 to T3 tumors with one to three involved lymph nodes, called N1
- Higher risk, T4 tumors or four or more involved lymph nodes, called N2
Three months was as good as six in lower-risk diseaseThe IDEA collaboration pooled six trials with 12,834 patients. In the lower-risk group, three-year disease-free survival was 83.1 percent after three months and 83.3 percent after six. In the higher-risk group, six months was better, 64.4 against 62.7 percent. Three months was clearly sufficient with CAPOX, a tablet-based cousin of FOLFOX, and less certainly so with FOLFOX itself. Grothey and colleagues, New England Journal of Medicine, 2018.
Advanced bowel, stomach and esophageal cancer
In advanced disease the aim shifts from cure to control, and FOLFOX becomes one step in a longer sequence that also includes FOLFIRI, antibodies chosen by the tumor's genes and, in selected patients, surgery or ablation for spread to the liver.
Order matters less than accessIn a French trial of 220 patients with advanced bowel cancer, FOLFIRI followed by FOLFOX6 gave a median survival of 21.5 months and the reverse order 20.6 months, no real difference. What matters is that patients receive both regimens during their illness. Tournigand and colleagues, Journal of Clinical Oncology, 2004.
Stomach and esophageal cancer, CheckMate 649
Before the first cycle
The port
A port makes the 46-hour pump possibleA small reservoir is placed under the skin below the collarbone, connected to a large vein, in a short procedure under local anesthetic. The pump needle goes into it each cycle, so the arm veins are spared and the drugs cannot leak into the skin. It stays in place for the whole course and is removed afterward.
Blood tests, and the DPD test
Blood counts, kidney and liver tests, the tumor marker CEA, and a test for DPD deficiency. The DPD enzyme breaks down fluorouracil. A small share of people carry a gene variant that lowers it, and at a full dose they can suffer severe, sometimes fatal toxicity. European regulators recommend testing before the first dose, and a positive result means a lower starting dose. Treatment still goes ahead.
One cycle, day by day
Fourteen days.
A cycle at a glance
Side effects, and the cold
Numbness usually fades, and in a few it staysIn MOSAIC, severe numbness affected 1.3 percent of patients a year after treatment and 0.7 percent four years after. Milder numbness is more common and improves over months to years after the last dose.
Length of stay, flying, cost and the trip
The honest arithmetic of a two-weekly regimen
Cost and the trip
Cost now sits elsewhere. FOLFOX drugs have aged into inexpensive generics, so the port, the day-unit time, the pump, blood tests, CT scans and any added antibody or immunotherapy make up most of the bill, and a patient on FOLFOX with bevacizumab or nivolumab pays mainly for the added drug. Published packages in Istanbul cover the consultation, the port, the first cycle, an interpreter and transfers. Hotel, flights and later cycles fall outside them, and we send a figure per cycle with the treatment plan after a free review of your reports.
The coordinator writes in your language.
English, Arabic, French, Russian, Serbian, Romanian or Spanish, or through an interpreter. The office sends the appointment confirmation and an invitation letter naming the hospital and the treating doctor ten days ahead, books the hotel and transfers, and arranges for two family members to join consultations if you wish. Meals come in halal, vegetarian and diabetic versions, a prayer room is on site, and a female doctor can be requested at the first contact.
Between cycles and after
Keep the written plan.
Once you are back home, your own oncologist takes over follow-up after the course. After colon cancer surgery that means a CEA blood test every three to six months and a CT scan every six to twelve months for the first three years, with a colonoscopy one year after the operation. Most recurrences that can still be cured are found this way.
Fever means the emergency department, the same hourA temperature of 38 degrees or higher in the second week after a cycle may mean infection with low white cells, which needs antibiotics within an hour. Go to the nearest emergency department and say that you are on chemotherapy.
This table scrolls sideways on a narrow screen. Swipe or drag to see every column.
| Sign | What it may mean | What to do |
|---|---|---|
| Fever of 38 degrees or chills | Infection with low white cells | Emergency department at once |
| More than four loose stools a day above normal | Fluorouracil diarrhea | Loperamide as instructed, call the team if it does not settle in a day |
| Mouth sores that stop eating or drinking | Mucositis | Call the team the same day |
| Redness, pain or swelling at the port | Port infection or clot | Call the team the same day |
| Chest pain during the pump | Rare fluorouracil effect on the heart arteries | Stop the pump if trained to, emergency department |
| Numbness that makes buttons or writing hard | Cumulative oxaliplatin nerve damage | Report before the next cycle so the dose can change |
FOLFOX Chemotherapy FAQ
What does FOLFOX stand for?
How long does FOLFOX treatment last?
Why do I need a pump and a port?
Why should I avoid cold drinks during FOLFOX?
Will the numbness in my hands and feet go away?
Can I have FOLFOX in Istanbul and continue at home?
References
- Andre T, Boni C, Navarro M, et al. Improved overall survival with oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment in stage II or III colon cancer in the MOSAIC trial. J Clin Oncol. 2009;27(19):3109-16.
- Grothey A, Sobrero AF, Shields AF, et al. Duration of Adjuvant Chemotherapy for Stage III Colon Cancer. N Engl J Med. 2018;378(13):1177-1188.
- Tournigand C, Andre T, Achille E, et al. FOLFIRI followed by FOLFOX6 or the reverse sequence in advanced colorectal cancer, a randomized GERCOR study. J Clin Oncol. 2004;22(2):229-37.
- Janjigian YY, Shitara K, Moehler M, et al. First-line nivolumab plus chemotherapy versus chemotherapy alone for advanced gastric, gastro-oesophageal junction, and oesophageal adenocarcinoma (CheckMate 649), a randomised, open-label, phase 3 trial. Lancet. 2021;398(10294):27-40.
Editor's note
Written by the Biruni Hospital medical editorial team. Reviewed by Prof. Dr. Özcan YILDIZ, Medical Oncology.
Medically reviewed by
Prof. Dr. Özcan YILDIZ
Medical Oncology
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