Adrucil (Fluorouracil) for Chemotherapy

Adrucil (fluorouracil) is a chemotherapy drug used for the treatment of breast cancer, colorectal cancer, pancreatic cancer, and stomach cancer. Approved by the U.S. Food and Drug Administration (FDA) in 1962 and included on the World Health Organization's List of Essential Medicines, Adrucil is widely used off-label to treat a variety of cancers, including cervical cancer and esophageal cancer.

Adrucil is delivered intravenously (into a vein), typically in combination with other chemotherapy drugs. In addition to the brand name Adrucil, fluorouracil is sold under the generic names 5-fluorouracil or 5-FU. There are also topical fluorouracil preparations used to treat certain skin cancers, sold under the brand names Carac, Efudex, Tolak, and Fluoroplex.

How It Works

Adrucil belongs to a category of chemotherapy drugs known as antimetabolites. Antimetabolites work by entering cancer cells and interfering with their ability to replicate. Adrucil does so by mimicking a compound known as pyrimidine that makes up the base of DNA. By infiltrating itself into a cancer cell's DNA, Adrucil prevents cellular division, thereby causing the cell to die.

Like many other chemotherapy drugs, Adrucil is cytotoxic (toxic to cells). It is able to target cancer cells because they replicate faster than normal cells. However, it cannot distinguish between cancer cells and other fast-replicating cells, such as blood cells, hair follicles, and cells of the mouth, stomach, and bowel.

This is why people on chemotherapy commonly experience anemia, hair loss, mouth sores, nausea, and diarrhea.

Who Can Take It

Adrucil is formally approved by the FDA to treat four types of cancer:

• Adenocarcinoma of the colon and rectum
• Adenocarcinoma of the breast
• Gastric adenocarcinoma
• Pancreatic adenocarcinoma

Adenocarcinoma is a type of cancer that forms in glandular tissues. It differs from other types of carcinoma, such as basal cell carcinoma (which forms in the lower layer of the epidermis) and squamous cell carcinoma (which form in the lining of organs, as well as the cells just beneath the outer epidermal layer). Carcinomas are the most common cancers in humans.

Off-Label Use

In real-world practice, however, Adrucil is used off-label to treat a wide variety of carcinomas, including those affecting the:

• Anus
• Bladder
• Cervix
• Esophagus
• Gallbladder
• Head and neck
• Liver
• Ovaries
• Penis
• Prostate
• Thymus

Dosage

Adrucil is supplied in a 50-milliliter (mL) vial at a dose of 50 milligrams per milliliters (mg/mL). It is delivered by intravenous (IV) infusion or injection. The dose varies by the cancer type and is dispensed in milligrams per body surface area (mg/m²). Body surface area is calculated based on weight in kilograms (kg) and height in centimeters (cm).

Breast Cancer

The recommended dose of Adrucil is 500 mg/m² or 600 mg/m² delivered intravenously on day 1 and day 8 of every 28-day cycle (six cycles in total).

Adrucil would be used as part of a multidrug therapy that would also include Cytoxan (cyclophosphamide).

Colorectal Cancer

The recommended dose of Adrucil is 400 mg/m² delivered by intravenous injection on the first day of treatment. This would be followed by a continuous IV infusion of 2,400 mg/m² to 3,000 mg/m² delivered over 46 hours every two weeks.

Adrucil would be used in combination with leucovorin (folinic acid) with or without Eloxatin (oxaliplatin) or Camptosar (irinotecan), depending on the stage of the colorectal cancer.

Stomach Cancer

The recommended dose of Adrucil is 200 mg/m² to 1,000 mg/m² delivered intravenously as a continuous IV infusion over 24 hours. The duration of the infusion would be largely based on the dose prescribed.

Adrucil would be used as part of a multidrug regimen that would also include a platinum-containing drug like cisplatin.

Pancreatic Cancer

The recommended dose of fluorouracil is 400 mg/m² by intravenous injection on day 1, followed by a continuous IV infusion of 2,400 mg/m² delivered over 46 hours every two weeks.

Adrucil would be used in combination with leucovorin with or without another chemotherapy drug, depending on the stage of the pancreatic cancer.

Side Effects

Like many cytotoxic chemotherapy drugs, Adrucil is known to cause a wide range of side effects, both mild and severe. The most common include:

• Nausea
• Vomiting
• Diarrhea
• Mucositis (gum inflammation)
• Anorexia (loss of appetite)
• Headache
• Fatigue
• Irritability or anxiety
• Depression
• Confusion
• Pruritus (itching)
• Alopecia (hair loss)
• Darkening of skin
• Brittle and discolored nails
• Easy bleeding or bruising
• Dyspnea (shortness of breath)
• Persistent hiccups
• Photosensitivity (also known as "sun allergy")
• Hand-foot syndrome (pain or numbness of the hands and feet)
• Maculopapular eruption (a rash covered with bumps that can form blisters)
• Increased risk of infection due to myelosuppression
• Impaired fertility in men due to toxic sperm damage

Adrucil can also cause cardiotoxicity, damage to the heart muscle caused by toxic drug exposure. Symptoms include dyspnea, angina (chest pain), and edema (fluid retention in the legs).

When to See a Healthcare Provider

Anaphylaxis, a serious, whole-body allergy, is rarely associated with Adrucil but can sometimes occur. Without exception, an anaphylactic reaction requires emergency medical treatment.

If left untreated, anaphylaxis can lead to coma, cardiac or respiratory failure, asphyxiation, and death.

You should also call your healthcare provider if any side effects are unexpectedly severe. These may include hallucinations, aphasia (an inability to speak and comprehend language), loss of bladder or bowel control, eyesight changes, or arrhythmia (heart rhythm disorders).

Drug Interactions

Adrucil may slow blood clotting due to the loss of platelets. This can enhance the effects of anticoagulants (blood thinners) like Coumadin (warfarin) used to prevent heart attacks, stroke, and blood clots. A dose adjustment of the anticoagulant may be needed if thrombocytopenia (low platelets) is diagnosed and/or excessive bleeding or bruising occurs.

Contraindications

Although there are no established contraindications for the use of Adrucil, it is typically avoided in people with severe bone marrow suppression caused by chemotherapy or radiation therapy. The risk of using Adrucil in this population of people may outweigh the benefits.

Adrucil is similarly avoided in pregnancy, as there is evidence it can harm a fetus, but it is not outright contraindicated. The evidence to date is based on animal studies in rats, mice, and monkeys. There are no well-controlled studies into the use of Adrucil in pregnant women.

Women of reproductive age should use contraception during Adrucil treatment and for three months after the completion of therapy. Speak to your healthcare provider about which forms of contraception are appropriate for you.

Coping

As difficult as chemotherapy can sometimes be, try not to anticipate side effects. Some people will respond to Adrucil better than others and may not experience the hair loss or other side effects that people generally worry about.

Even if you do, there are things you can do to cope:

• Moisturize your skin several times daily to reduce itchiness.
• Avoid sun exposure, and use sunscreen when outdoors.
• Do not apply topical ointments to a rash unless your healthcare provider gives you the OK.
• Eat smaller, frequent meals to better deal with nausea and the loss of appetite.
• Eat high-calorie foods such as pudding, ice cream, yogurt, milkshakes, and protein shakes.
• Drink a minimum of eight 8-ounce glasses of water per day (more if you are experiencing diarrhea or vomiting).
• Gently clean your teeth with a soft toothbrush after each meal. Rinse your mouth with 1/2 teaspoon of salt or baking soda mixed in 8 ounces of water.
• Avoid alcohol and smoking if you have mouth sores.
• To lessen the impact of fatigue, pace yourself by scheduling regular rest breaks throughout the day.
• To help decrease your risk of infections, wash your hands regularly.
• Avoid close contact with people who have a cold, the flu, or other infections.
• Avoid washing your hair every day to reduce hair loss.
• Use a mild shampoo and pat (rather than rub) your scalp dry.
• Limit your use of hair spray, curling irons, or blow driers.
• Do not color or perm your hair.
• Keep your nails and nail beds moisturized.