FOLFOX for Colon and Stomach Cancer Treatment: Folinic Acid, Fluorouracil, Oxaliplatin

FOLFOX ( Folinic acid + Fluorouracil + Oxaliplatin ) colon cancer and stomach cancer are treated with this chemotherapy regimen.

How does FOLFOX work?

Each chemotherapy drug in FOLFOX is designed to kill colon ( large intestine ) and stomach cancer cells.

FOL – folinic acid ( leucovorin = leucovorin )

F – luorouracil

OX – oxaliplatin

Purpose of treatment

-The FOLFOX chemotherapy regimen is given to shrink tumors and reduce the signs and symptoms associated with colon and stomach cancer.

- If the disease is not metastatic, the general treatment is preventive therapy after surgery to reduce the likelihood of cancer recurrence ( adjuvant ) treatment.

- If it is stage 4. disease that has spread to other organs through metastasis from colon or stomach cancer, FOLFOX is generally given to prolong survival and improve quality of life, rather than to achieve a complete cure.

Administration dose and schedule

- Also called calcium folinate, folinic acid is given at a dose of 400 mg/m2, over at least 2 hours, slowly through a vein ( İntreVenöz = İ. V. ). Giving a drug through a vein over a specified period in this way is called an infusion . Folinic acid is given on day 1, before fluorouracil.

- Oxiplatin is given at a dose of 85 mg/m2, through a vein, on day 1, over at least 2 hours. It can be given together with folinic acid.

- Push administration is the name we give to short-duration, low-dose administration of Fluorouracil at a dose of 400 mg/m2, through a vein, on day 1, after completion of the folinic acid infusion, usually over 5-10 minutes.

- Maintenance Fluorouracil is given at a dose of 2400 mg/m2, through a vein, starting on day 1 and ending on day 3, as an infusion lasting approximately 46 hours (usually with an infusion pump at home).

Estimated infusion time for FOLFOX

- On day 1, treatment administered in the outpatient chemotherapy center takes 4-6 hours. The patient is then sent home with an infusion pump and returns 2 days later to have it removed. Patients too ill to receive treatment at home, or requiring medical monitoring for other reasons, can also receive this chemotherapy regimen as hospital inpatients.

- Infusion times are determined according to clinical studies, but may vary depending on doctors' preferences or the patient's condition. Intravenous fluids given before chemotherapy, such as hydration, may change the duration.

- FOLFOX is repeated every 14 days. Each 14-day period is called 1 cycle of chemotherapy . If the disease is not metastatic, treatment is given for 6 cycles ( 3 months ) or 12 cycles ( 6 months ). In stage 4. colon and stomach cancer, it is repeated as long as the patient responds to treatment or until unacceptable side effects occur.

Side effects

In multidrug regimens, each drug has separate side effects. This article includes the most common side effects of FOLFOX identified during clinical studies. Side effects are sometimes expressed as percentage ranges (for example: %37-92), because results in clinical studies varied within these ranges.

• Tingling or burning in the arms and legs ( neuropathy ), usually mild (% 37 - 92)
• Low white blood cell counts ( neutropenia ) (% 58 - 79)
• Increased bleeding risk ( low platelet count; thrombocytopenia ) (% 23 - 77)
• Anemia ( low red blood cell counts ) (% 76)
• Nausea * (64 - 74%)
• Diarrhea (% 56 - 61) 
• Vomiting * (% 39 - 47)
• Weakness (% 45)
• Mouth sores ( mucositis ) (% 37 - 42) 
• Loss of appetite (% 30) 
• Hair loss ** (% 28) 
• Constipation (% 28)
• Fever (% 26) 
• Abdominal pain (% 26)
• Muscle weakness (% 20) 
• Rashes on the palms and soles (% 10) 
• Allergic reaction (% 10)
• Blood clots ( thrombosis ) (% 6) 
• Neutropenic fever ( fever with low white blood cell counts ) (% 2)

If FOLFOX is given for metastatic disease, an average of nearly %25 of patients cannot continue treatment because side effects increase over time. If the disease is not metastatic, meaning treatment is given after surgery for preventive ( adjuvant ) purposes, most patients can complete the planned treatment.

* Thanks to the development of effective anti-nausea and anti-vomiting medicines, the percentage experiencing nausea or vomiting is lower today, according to newly reported clinical studies;

** Hair loss caused by FOLFOX is generally mild, and most often it is visible only on careful, close examination. It can be covered with a different hairstyle or way of combing the hair. A wig or hairpiece is generally unnecessary.

NOTE: Toward the end of or after FOLFOX treatment, the frequency of severe tingling, pain, burning or numbness in the hands or feet, which we call neuropathy, is around % 1. In most patients, these effects diminish within 28 days after treatment ends, but very rarely these symptoms can continue for 1 year or become permanent.

Follow-up

How frequently is follow-up necessary?

Laboratory tests ( blood tests ) must be performed before each treatment. The requested tests generally include a complete blood count ( hemogram ), a comprehensive metabolic panel ( biochemistry ) and other tests your doctor may recommend. If CEA ( carcinoembryonic antigen ) is positive at diagnosis, checking this blood test every six weeks may make it possible to monitor the tumor's response to FOLFOX.

How frequently is imaging ( radiological examination ) necessary?

Imaging methods such as computed tomography ( BT ), magnetic resonance ( MR ) or PET-BT are performed before treatment and at certain intervals during treatment. Imaging is performed less frequently in patients receiving FOLFOX as preventive treatment after surgery; more frequent imaging ( for example, every 2 months ) may be performed to measure whether metastatic disease is responding to treatment.

How do blood test or imaging results affect treatment?

Depending on the results, your doctor may recommend continuing FOLFOX as initially planned, reduce drug doses according to side effects or request that the next dose be postponed. The chemotherapy regimen may also be changed. If persistent tingling, pain, numbness or burning occurs in the fingers and toes ( lasting more than 14 days ), the oxaliplatin dose may be reduced. If the number of white blood cells known as neutrophils falls, the platelet count decreases, or side effects such as severe mouth sores or diarrhea occur, fluorouracil and/or oxaliplatin doses may be reduced. Your doctor determines dose reductions.

Points to consider

• Oxaliplatin treatment can increase your sensitivity to cold things, such as cold drinks and cold air. Therefore, during the 2 days after treatment you can choose clothing that keeps you warm, and you are advised not to consume cold or iced drinks.
• Fluorouracil can cause rashes on the hands and feet, known as hand-foot syndrome. To help reduce the risk of hand-foot syndrome, you can use an alcohol-free moisturizer on your hands and feet daily. It is important to avoid prolonged exposure to hot water. While using fluorouracil, avoid tasks that create pressure or friction on your hands and feet. 
• If your white blood cells, important elements of the immune system, become very low, an injection of a white blood cell growth factor ( such as filgrastim, lenogastrim or pegfilgastrim ) may be needed after chemotherapy to stimulate production of these cells, called leukocytes, and avoid neutropenia. This is usually done if the disease is not metastatic. If the disease is metastatic, these drugs are not routinely given; instead, FOLFOX treatment is postponed until white blood cell counts recover.

Individual drug label information

Calcium folinate = folinic acid

• Folinic acid is a derivative of vitamin B9 , folic acid. Unlike other chemotherapy drugs, it does not directly kill cells; it acts by increasing fluorouracil activity.
• It is light yellow in color. 
• It is available under names such as Calcium Folinate, Folca, Leucovorin and Kalsiyum Folinat.

General side effects of folinic acid

• Common side effects: nausea, mouth sores
• Uncommon side effects: fever
• Rare side effects: insomnia, seizures and fainting ( syncope )

Fluorouracil

• Fluorouracil (5-FU) is a chemotherapy drug in the antimetabolite class, known as a pyrimidine analogue. DNA synthesis involves an enzyme that it disrupts to exert its anti-cancer effect.
• It is available under names such as 5-Fluorouracil, 5-Frotu, Fivoflu, Fluorouracil and Fluro-5.

General side effects of fluorouracil

• Low white blood cell count (leukopenia and neutropenia)
• Sores or ulcers in the mouth and throat (mucositis)
• Diarrhea
• Nausea and vomiting
• Low red blood cell and platelet counts
• Allergic reactions, rarely
• Eye pain, light sensitivity, excessive watering, visual changes
• Headache
• Skin changes: dryness, redness, tingling, light sensitivity, pain, swelling, loss of nails (hand-foot syndrome)
• Dose adjustments may be necessary for severe liver dysfunction

Oxaliplatin

• Oxaliplatin belongs to the same platinum group as cisplatin and and carboplatin and is a platinum-based chemotherapy. It binds to the nucleotides called guanine and cytosine in DNA, causing cross-links, and exhibits anti-cancer properties by preventing DNA synthesis and replication.
• Allergic reactions that can occur within a few minutes have been reported. Medicines such as antihistamines, corticosteroids or epinephrine can be given to relieve symptoms.
• Oxaliplatin is generally given in a %5 dextrose solution.
• In patients with liver dysfunction, the infusion duration should be increased beyond 2 hours.
• It is available under names such as Curatinox, Eloxatin, Linox, Oxalidem, Oxalimedac, Oxaliplatin, Oxalpin, Oxatu, Oxebewe and Ploxal.

General side effects of oxaliplatin

• Tingling or burning in the feet and hands, loss of tendon reflexes (neuropathy)
• Sensitivity to cold air and cold drinks may occur for a few days after oxaliplatin administration. Wearing warm clothing in cold weather and avoiding cold drinks are recommended.
• Lung toxicity should be considered when coughing or breathing difficulties occur during treatment.
• Low white blood cell, platelet and red blood cell counts
• Constipation
• Diarrhea
• Vomiting or nausea
• Fatigue
• Mouth sores
• Changes in liver function
• Avoid use during pregnancy; it is known to harm the fetus
• Be sure to tell your physician about other medicines you use because of possible drug interactions.