Understanding FOLFOX Chemotherapy : Treatment Protocol, Effectiveness, and Side Effects

1. Introduction

   1. What is Chemotherapy and its Purpose?

      Chemotherapy is a medical treatment in which drugs are used to kill or slow down the growth of rapidly growing cells, particularly cancer cells. The drug administered circulates throughout the body via the bloodstream. It targets both primary tumors and potential metastatic cancer cells.

      The purpose of chemotherapy is to eliminate cancer cells and inhibit their growth. It is administered with the intent to eradicate cancer cells and achieve long-term remission or cure. It is sometimes given as an adjuvant therapy after surgical removal of the tumor and radiation therapy.

   2. What is FOLFOX Chemotherapy?

      FOLFOX chemotherapy is a combination treatment used primarily for the treatment of colorectal cancer. It is a combination of chemotherapy drugs 5-fluorouracil (5-FU), oxaliplatin, and leucovorin (Folinic acid). FOLFOX is derived from ‘FOL’ Folinic acid and ‘FOX’ from 5-fluorouracil and oxaliplatin.

      FOLFOX works by targeting and destroying cancer cells through different mechanisms.

      • 5-fluorouracil is a cytotoxic drug that inhibits the growth of cancer cells by interfering with the ability to replicate their DNA. It is administered continuously through an infusion pump over a period of 46-48 hours.
      • Oxaliplatin is platinum-based chemotherapy that works by damaging the DNA of cancer cells and preventing their division and multiplication.
      • Leucovorin (Folinic Acid) is a folate analog that enhances the effectiveness of 5-FU by increasing its anticancer activity.

      FOLFOX chemotherapy regimen is administered in cycles with each cycle lasting for several weeks. The frequency and duration depend on the stage and type of cancer and the patient’s individual condition. FOLFOX chemotherapy has been shown to be effective in treating colorectal cancer both in the adjuvant and metastatic setting.⁽¹⁾ It can also be helpful in the treatment of other types of cancers.⁽²⁾ It may be useful in treating pancreatic cancer and other cancers.⁽³⁾

2. Administration and Treatment Protocol of FOLFOX Chemotherapy

   The following aspects are involved in the treatment protocol of FOLFOX chemotherapy:

   • Pretreatment Evaluation: A thorough evaluation is conducted by the healthcare team which involves taking medical history, physical examination, and relevant laboratory tests. The overall health status of the patient is determined, organ functions are assessed, and potential risks and complications are identified.
   • Dosage and Administration: FOLFOX chemotherapy is administered intravenously. The dosage and administration schedule may vary depending on the individual patient and the treating physician’s recommendations. Oxaliplatin is administered intravenously over a period, usually lasting for a few hours. Leucovorin is administered before 5-FU to enhance its effectiveness. The duration of infusion may vary. 5-FU is then administered. This includes continuous infusion via a proton pump or as a bolus injection.
   • Treatment Cycles and Duration: FOLFOX chemotherapy is typically administered in cycles and each cycle lasts for a specific period followed by a resting period. There may be several cycles scheduled over several months. The exact duration and number of cycles may depend on cancer type, stage, treatment goals, and individual patient response.
   • Dose Adjustments and Modifications: During the course of FOLFOX chemotherapy the healthcare team assess any potential side effects and minimize adverse effect. The dose adjustment is made based on individual patient factors which include the blood count, organ function, and tolerability.
   • Supportive Care: In FOLFOX chemotherapy measures are implemented to manage potential side effects and maintain the patient’s well-being. Medications to prevent nausea and vomiting may be given.

   Specific administration and treatment protocol for FOLFOX chemotherapy can vary depending on the healthcare provider and patient’s individual characteristics, and treatment goals. For the best possible outcome, the healthcare team may provide detailed instructions and closely monitor the patient to ensure the best possible outcome.

3. How Effective is FOLFOX Chemotherapy?

   Treatment of colorectal cancer usually involves the surgical removal of the colon. Chemotherapy is given post-surgical removal to kill the remaining cancer cells. FOLFOX therapy can be a good option for people with colorectal cancer.

   A study done in 2016 looked for FOLFOX chemotherapy as an adjuvant treatment. In 213 participants with stage 3 colon cancer, the 5-year overall survival rate was 77.9%. It was observed that FOLFOX chemotherapy significantly increased the survival rate in people receiving at least eight cycles.⁽⁴⁾

   A study done in 2019 compared FOLFOX with an alternative regimen called FOLFIRI in people with colon cancer. No significant difference was observed in the survival rate between the two treatments. however, FOLFOX was noted to have fewer side effects and was cost-effective.⁽⁷⁾ Another study, done in 2020 determined that FOLFOX could effectively treat aggressive pancreatic neuroendocrine tumors in people receiving capecitabine and temozolomide.⁽³⁾

   One more study was done in 2020 that compared the effectiveness of 3 months to 6 months of adjuvant chemotherapy using FOLFOX. In the 3-month group the 5-year survival rate was observed to be 82.6% while in the 6-month group, it was observed as 83.8%.⁽⁸⁾

4. Side Effects and Management of FOLFOX Chemotherapy

   1. Common Side Effects and Their Management

      The side effects due to FOLFOX chemotherapy may vary in severity. 1 in 5 individuals receiving FOLFOX therapy develop some or all side effects and symptoms.⁽⁵⁾ The common side effects include:

      • There may be nausea and occasional vomiting. Anti-nausea medications are given and the patient is advised to eat small frequent meals.
      • Fatigue, which may last for a few days post-treatment. It is managed by balancing rest and physical activity and eating a well-balanced diet.
      • Diarrhea may range from mild to severe. Advice is given to drink plenty of water and avoid caffeine and alcohol.
      • The patient may experience tingling, numbness, or pain in the hands and feet. Engaging in gentle exercises can manage these symptoms.
      • The individual may feel sensitive to cold temperatures that may cause discomfort or pain in the hands, feet, and throat upon being exposed to cold objects and liquids. Using warm water for washing hands and avoiding ice-cold beverages can help.
      • FOLFOX therapy may decrease the blood cell and platelet count. The patient is advised to report any signs of infection and maintain good personal hygiene.
      • There may be hair thinning which may not be as severe as other chemotherapy regimens. The person is prepared for hair loss by considering hats, wigs, and scarves.
      • There may be gastrointestinal symptoms such as constipation, abdominal pain, indigestion, or a change in taste sensation. Staying hydrated, maintain a well-balanced diet with adequate fiber intake can help alleviate the symptoms.
      • Individuals may also experience allergic reactions. These may include rash, difficulty breathing, irritability, or swelling on the face, lips, or throat. Antihistamines are prescribed to manage allergic reactions.

      People who develop side effects should discuss their treatment regimen with the doctor. A study was done in 2018 on 109 individuals with stage 4 colon cancer. It stated that the doctors reduced the dose in half of the patients after side effects were seen.⁽⁶⁾ It was observed that despite lowering the dose no difference was observed in overall survival between individuals receiving an adjusted lower dose and those on a higher initial dose.

   2. Long-Term Effects and Considerations

      Just like other chemotherapy regimens, there may be long-term effects and consideration of FOLFOX chemotherapy as well.

      • The peripheral neuropathy may persist or may even worsen after treatment.
      • Some individuals may experience cognitive changes referred to as chemo brain or chemo fog. There may be difficulty in memory, concentration, and mental clarity.
      • People undergoing chemotherapy may also experience anxiety, depression, fear or recurrence, or adjustment difficulties.
      • There may be fertility issues in both men and women.
      • In rare cases, Oxaliplatin may cause cardiotoxic effects that may lead to heart problems.

      FOLFOX chemotherapy may affect the overall quality of life of a person.

FOLFOX chemotherapy regimen is commonly recommended by doctors for the treatment of colorectal cancer. It contains folinic acid, fluorouracil, and oxaliplatin. It can improve the individual’s outlook. It may cause unpleasant side effects. If an individual experiences side effects, they can discuss with the doctor to get the dose adjusted.