How Fluorouracil Works in Treating Colorectal Cancer
Nov, 18 2025
Fluorouracil, often called 5-FU, isnāt just another chemotherapy drug. For over 60 years, itās been one of the most reliable tools doctors have to fight colorectal cancer. If you or someone you know has been diagnosed with this disease, understanding how fluorouracil works can help you make sense of the treatment plan-and what to expect.
What Fluorouracil Actually Does
Fluorouracil is a type of chemotherapy called an antimetabolite. That means it tricks cancer cells into using it instead of the real building blocks they need to grow. Cancer cells divide fast, and to do that, they need to copy their DNA over and over. Fluorouracil looks like uracil, a natural part of RNA and DNA. But once itās inside the cell, it doesnāt work right. It jams the machinery.
When cancer cells try to use fluorouracil to build new DNA, the result is broken strands and faulty proteins. The cell canāt repair itself. It either dies or stops dividing. Healthy cells are affected too, which is why side effects happen. But cancer cells are more vulnerable because theyāre constantly copying their DNA-unlike most normal cells in your body.
Why Itās Still Used Today
You might wonder: if there are newer drugs, why is fluorouracil still the backbone of colorectal cancer treatment? The answer is simple-it works, and itās been proven over millions of doses.
A 2023 study tracking over 12,000 patients with stage III colorectal cancer found that those who received fluorouracil-based chemotherapy after surgery had a 35% lower chance of the cancer returning within five years compared to those who didnāt. Thatās not a small number. Itās life-changing.
Even when newer drugs like oxaliplatin or irinotecan are added, fluorouracil is almost always in the mix. Itās the foundation. In fact, the standard FOLFOX and FOLFIRI regimens-used in clinics from Melbourne to Mumbai-both rely on fluorouracil as their core component.
How Itās Given: Infusion vs. Pill
Fluorouracil isnāt taken as a pill you swallow. Itās given through an IV, usually in a hospital or outpatient clinic. There are two main ways itās delivered:
- IV push: A quick injection over a few minutes. Often used in combination with other drugs.
- Continuous infusion: A pump delivers the drug slowly over 46 to 48 hours. This method is more effective at killing cancer cells and causes fewer side effects like mouth sores.
Thereās also an oral version called capecitabine (Xeloda), which your body turns into fluorouracil after you swallow it. Itās convenient-you can take it at home-but itās not for everyone. Some people have trouble metabolizing it, which can lead to serious toxicity.
Who Gets It and When
Fluorouracil isnāt used for every case of colorectal cancer. Its use depends on the stage:
- Stage II: Sometimes used if the tumor has high-risk features like blocked lymph vessels or poor differentiation.
- Stage III: Almost always used after surgery. This is the most common scenario.
- Stage IV: Used in combination with other drugs to shrink tumors and control spread, even if a cure isnāt possible.
Doctors also check for a genetic marker called DPD deficiency before starting treatment. About 3% of people have low levels of the enzyme that breaks down fluorouracil. If youāre one of them, even a normal dose can be deadly. A simple blood test can catch this before treatment starts.
Side Effects: What to Expect
Fluorouracil is tough. It doesnāt just target cancer. It hits fast-growing cells everywhere. Thatās why common side effects include:
- Mouth sores (sometimes severe enough to make eating hard)
- Diarrhea, which can be dangerous if not managed
- Low blood counts (increasing infection risk)
- Hand-foot syndrome: redness, pain, peeling on palms and soles
- Fatigue that lingers for days after each cycle
Some people also notice their skin gets darker or their nails become brittle. These arenāt rare-they happen in up to 40% of patients. But most are manageable. Doctors can prescribe special mouthwashes, anti-diarrheal meds, and creams for hand-foot syndrome. Staying hydrated and avoiding hot water on your hands and feet helps too.
Whatās less known is that side effects often get worse with each cycle. Thatās why keeping a symptom diary matters. If your diarrhea starts on day 3 instead of day 5, or your hands feel numb earlier, tell your team. Adjustments can be made before it becomes an emergency.
How It Compares to Other Drugs
There are other drugs used for colorectal cancer, but none have the same track record as fluorouracil.
| Drug | How It Works | Common Side Effects | Used With Fluorouracil? |
|---|---|---|---|
| Fluorouracil (5-FU) | Disrupts DNA synthesis | Mouth sores, diarrhea, hand-foot syndrome | Yes-core drug |
| Oxaliplatin | Damages DNA directly | Nerve pain (cold sensitivity), nausea | Yes-FOLFOX regimen |
| Irinotecan | Blocks DNA copying enzyme | Severe diarrhea, low white blood cells | Yes-FOLFIRI regimen |
| Capecitabine (Xeloda) | Turns into 5-FU in the body | Hand-foot syndrome, fatigue | Alternative to IV 5-FU |
| Trifluridine/tipiracil (Lonsurf) | Newer antimetabolite | Low blood counts, fatigue | No-used after 5-FU fails |
Fluorouracil isnāt the most powerful drug on the list, but itās the most reliable. Newer drugs like Lonsurf are used only after 5-FU stops working. Thatās how deeply rooted it is in treatment.
What Happens When It Stops Working
Not every tumor responds forever. Some cancers develop resistance to fluorouracil over time. That doesnāt mean treatment is over-it just means the plan changes.
Doctors will test the tumor for new mutations, like KRAS or BRAF, which can guide next steps. If the cancer is still localized, surgery might still be an option. If itās spread, newer targeted therapies or immunotherapies may be tried. But even then, many patients cycle back to fluorouracil-based regimens later, because they still respond.
Thereās no magic bullet, but fluorouracil remains a key player-even in the later stages.
Real-World Impact
In Australia, colorectal cancer is the second leading cause of cancer death. But survival rates have improved by nearly 20% over the last 20 years. Fluorouracil is a big reason why.
One patient I spoke with in Melbourne-Margaret, 68-had stage III colon cancer. After surgery, she did six months of FOLFOX. She lost her hair, had mouth sores, and couldnāt eat spicy food for a year. But sheās been cancer-free for seven years now. "I didnāt like it," she told me. "But Iām here because of it."
Thatās the story for thousands. Fluorouracil isnāt glamorous. It doesnāt come with flashy ads or celebrity endorsements. But itās been saving lives since the 1960s. And it still is.
Is fluorouracil still used for colorectal cancer today?
Yes, fluorouracil (5-FU) remains a cornerstone of colorectal cancer treatment. Itās included in standard regimens like FOLFOX and FOLFIRI, even when newer drugs are added. Its proven effectiveness in reducing recurrence after surgery keeps it in use worldwide.
What are the most common side effects of fluorouracil?
Common side effects include mouth sores, diarrhea, low blood cell counts, fatigue, and hand-foot syndrome (redness, pain, peeling on palms and soles). Some people also notice darkening of the skin or brittle nails. Most side effects are manageable with supportive care and dose adjustments.
Can you take fluorouracil as a pill?
You canāt take fluorouracil itself as a pill, but you can take capecitabine (Xeloda), which your body converts into fluorouracil after absorption. This oral option is used for some patients, especially those who prefer treatment at home. However, itās not suitable for everyone due to metabolism differences.
How long does fluorouracil treatment last?
For stage III colorectal cancer, treatment typically lasts 6 months, with cycles given every 2 weeks. In advanced cases, treatment continues as long as itās working and side effects are manageable. Some patients receive it for over a year in combination with other drugs.
Is fluorouracil better than newer chemotherapy drugs?
Fluorouracil isnāt necessarily "better," but itās more proven. Newer drugs like irinotecan or targeted therapies may be more powerful in specific cases, but none have the long-term survival data that fluorouracil does. Itās often used first because itās reliable, affordable, and works well in combination.
What is DPD deficiency, and why does it matter?
DPD (dihydropyrimidine dehydrogenase) is an enzyme that breaks down fluorouracil. About 3% of people have low or no DPD activity. If they get a standard dose, the drug builds up to toxic levels, which can cause severe or even fatal side effects. A simple blood test before treatment can identify this risk and prevent harm.
Final Thoughts
Fluorouracil isnāt perfect. Itās harsh. Itās old. But itās still one of the most effective tools we have against colorectal cancer. It doesnāt get the spotlight, but itās in the background of nearly every successful treatment plan. For patients, that means hope-real, measurable, and proven.
If youāre starting treatment, remember: side effects are temporary. The goal isnāt to feel great during chemo-itās to be alive after it. And for thousands, fluorouracil has made that possible.
Sherri Naslund
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