What Is FOLFOX Chemotherapy?

Chemotherapy is a medication used to kill cancer cells or stop cancer cells from growing. These medications work in different ways to help treat cancer. Chemotherapy regimens can include just one medication or a combination of a few medications. Chemotherapy can also be combined with other cancer treatments, such as surgeries or non-chemotherapy medications, to help make the treatment more effective.

There are many chemotherapy regimens out there. Among many factors, the type of cancer a person has helps a healthcare provider decide which regimen would be best for a person. A common chemotherapy regimen used for colorectal cancer is FOLFOX.

Here, we’ll discuss what FOLFOX is and what to expect should you or a loved one be prescribed this regimen.

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What does FOLFOX stand for? 

FOLFOX is an abbreviation. It stands for the three medications that make up this chemotherapy regimen. Those medications include:

• Leucovorin (also called folinic acid): This is the “FOL” part of the abbreviation. Leucovorin is a form of vitamin B9.

• 5-fluorouracil (5-FU): This is the second “F” in the abbreviation. 5-FU is a chemotherapy medication.

• Oxaliplatin: This is the “OX” at the end of the abbreviation. Oxaliplatin is a chemotherapy medication.

FOLFOX can also sometimes have numbers that follow the abbreviation, such as FOLFOX-4 or FOLFOX-6. These numbers refer to the exact dose of medication being used and how often they’re given.

What type of cancer does FOLFOX treat?

The most common type of cancer that FOLFOX is used for is colorectal cancer. However, it may also be used for other cancers, such as:

• Pancreatic cancer

• Gastric cancer (stomach cancer)

• Esophageal cancer (cancer of the tube that connects your mouth and stomach)

• Biliary cancer (a type of liver cancer)

FOLFOX is commonly used in colorectal cancer because of the results from a research study called the MOSAIC trial. This clinical trial compared using 5-FU and leucovorin to using the FOLFOX combination for people with stage 2 or 3 colorectal cancer.

In the MOSAIC trial, FOLFOX slowed the growth and spread of cancer cells more effectively for people with stage 3 colorectal cancer than the combination of 5-FU and leucovorin. It wasn’t as helpful for people with stage 2 colorectal cancer.

FOLFOX is also commonly used for stage 4 colorectal cancer. For people with more advanced stages of cancer, FOLFOX is used as a palliative treatment. This means that it can help lessen symptoms or improve a person’s quality of life.

How is the FOLFOX regimen given?

The FOLFOX regimen is an intravenous (IV) infusion, meaning it’s slowly given directly in a vein. Most of the FOLFOX medications should be given at an infusion center, either at an oncologist's (cancer specialist’s) office or at a hospital. This is because a healthcare provider or nurse will very closely watch you for allergic reactions and side effects during your infusion. 

There are a few different FOLFOX regimens that can be used. They vary in medication strength and how often they’re given. However, they often include two separate doses of 5-FU. The first dose is called an IV bolus dose. The second dose is called a continuous infusion.

An IV bolus means the medication is given quickly over a shorter period of time. A continuous infusion means it’s given slowly over a longer period of time. The purpose of giving both a bolus dose and continuous infusion of 5-FU is to provide longer exposure to the medication. This means 5-FU will be around in your body longer to kill cancer cells.

Some people may be unable to tolerate the side effects from the bolus dose of 5-FU. If this is the case, your healthcare provider may only give you the continuous 5-FU infusion. This decision would be personalized based on your response to FOLFOX.

How long does the infusion take?

You’ll likely be at the infusion center receiving medications for about 4 to 6 hours at a time. Then, you’ll be sent home with a medication pump. This pump will slowly infuse 5-FU over the next few days.

Once the pump is done infusing 5-FU, you may have to return to the infusion center to have it removed. Some facilities send a nurse to your house to disconnect the pump so you don’t have to make a second trip. This varies between healthcare facilities.

How often and how long you’ll receive FOLFOX is individualized. Your regimen may be adjusted based on your response and the side effects you experience. It’s common to receive FOLFOX for 3 to 6 months.

Discuss your regimen with your oncologist before your first FOLFOX treatment. They can let you know details that are unique to you and the infusion center you’ll be using.

What are the side effects of FOLFOX chemotherapy?

Everyone tolerates chemotherapy differently. There may be some who don’t experience many side effects and others who experience a lot. Below we’ll discuss potential side effects of each FOLFOX medication. Be sure to let your oncologist know what you experience after your treatments.

Possible side effects of 5-FU include:

• Sensitivity to the sun

• Redness, pain, or peeling on the hands and feet (hand-foot syndrome)

• Mouth sores

• Nausea and vomiting

• Diarrhea (can be severe)

• Low numbers of white blood cells, red blood cells, or platelets

• Heart problems or damage

The most common side effects of oxaliplatin include:

• Cold sensitivity

• Thinning of the hair (hair loss is less common)

• Numbness and tingling in hands and feet (peripheral neuropathy)

• Tiredness

• Low numbers of white blood cells, red blood cells, or platelets

• Nausea and vomiting

• Diarrhea

• Mouth sores

• Changes to liver blood tests

Leucovorin isn’t known to cause any side effects on its own. This is most likely because leucovorin is typically given with chemotherapy medications. So it’s difficult to say which side effects are coming from leucovorin and which are coming from the chemotherapy.

However, it’s possible to have an allergic reaction during or after your leucovorin infusion. Symptoms of an allergic reaction include hives, trouble breathing, or swelling of the face or neck. You’ll be monitored for these reactions while at the infusion center.

How effective is FOLFOX?

The effectiveness of FOLFOX varies, depending on the type and stage of cancer a person has. For stage 4 colorectal cancer, the goal of treatment is to lessen symptoms — not cure the cancer. But when used to treat stage 3 colorectal cancer, studies suggest FOLFOX is an effective combination. 

In the MOSAIC trial discussed earlier, 78% of participants using FOLFOX had disease-free survival after 3 years of using the regimen. This means there was no sign of cancer for 3 years after completing FOLFOX treatment. Researchers also noted that using FOLFOX lowered the risk of cancer returning by 23% compared to only using 5-FU and leucovorin.

Another smaller study of people with stage 3 colorectal cancer found similar results. In this study, about 77% of study participants experienced disease-free survival for 3 years after using FOLFOX.

Both of these studies suggest FOLFOX is an effective treatment combination for stage 3 colorectal cancer.

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Written by:

Sonia Amin Thomas, PharmD, BCOP

Sonia Amin Thomas, PharmD, BCOP, has been practicing as a clinical pharmacist for 12 years and in oncology pharmacy for over 10 years. She practices both academic and clinical pharmacy and is board certified as an oncology pharmacist and integrative health coach.

Edited by:

Christina Aungst, PharmD

Christina Aungst, PharmD, is a pharmacy editor for GoodRx. She began writing for GoodRx Health in 2019, transitioning from freelance writer to editor in 2021.

Reviewed by:

John Strickler, MD

John Strickler, MD, joined the Duke University faculty in 2011 and is now an associate professor of medicine in the division of medical oncology. His research focuses on precision cancer medicine: identification of genomic biomarkers that predict sensitivity or resistance to targeted therapies and immunotherapy.

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