Amifostine

Definition

Amifostine, also known as the brand name Ethyol and as ethiofos or WR2721, is a medicine that helps protect certain tissues of the body from damage caused by chemotherapy or radiation therapy.

Purpose

Amifostine is a protectant agent that is used in combination with the chemotherapy drug cisplatin or in combination with radiation therapy. Amifostine is approved by the Food and Drug Administration (FDA) to prevent kidney damage caused by repeat doses of the chemotherapy agent cisplatin in patients who have a diagnosis of ovarian cancer or non-small cell lung cancer. It is also FDA approved for patients with head and neck cancer who are receiving radiation therapy after surgery. In this group of patients, amifostine helps decrease radiation damage to the salivary glands, which can cause dry mouth.

Description

Amifostine has been on the market since the mid-1990s. A clear colorless solution, it is administered into a vein before chemotherapy and has been shown to decrease kidney damage by greater than 50% in advanced ovarian cancer patients who have received multiple cycles of cisplatin. It is also used before radiation therapy to prevent damage to the salivary gland known as the parotid gland.

When cisplatin is given to patients, it becomes broken down into toxic substances that destroy cancer cells and normal cells. When amifostine is administered into the body, it is broken down by an enzyme that occurs in large quantities in normal cells but not in cancerous cells. It then is converted into a substance called free thiol, which combines with the poisonous cisplatin by-products in the normal cells and makes them nontoxic.

In patients who receive radiation to the mouth area, including the salivary glands, the radiation causes the release of substances called free oxygen species, which damage cells of the mouth. An enzyme in cells of the mouth breaks down amifostine into a substance called free thiol. The free thiol blocks the free oxygen substances from damaging the salivary cells and decreases the amount of dry mouth patients suffer from when they receive radiation to the head and neck area.

Recommended dosage

Before dosing amifostine in chemotherapy or radiation therapy patients, intravenous fluids need to be given to keep the body well flushed with fluid and to maintain a normal blood pressure. All patients will receive amifostine lying down, sometimes with the head of the body lower than the feet. Patients should also receive medication to help prevent the nausea and vomiting that occurs due to amifostine.

Amifostine dosages can be determined using a mathematical calculation that measures a person's body surface area (BSA). This number is dependent upon a patient's height and weight. The larger the person, the greater the body surface area. Body surface area is measured in units known as square meter (m²). To determine the actual dose a patient is to receive, the body surface area is calculated and then multiplied by the drug dosage in milligrams per squared meter (mg/m²).

The recommended dosage of amifostine for protection of the kidney is 910mg/m² administered as a 15-minute infusion into a vein. This is to begin 30 minutes before chemotherapy administration. If a patient has difficulty with this dose, the dosage can be lowered to 740 mg/m².

The recommended dosage of amifostine for radiation therapy patients is 200 mg/m² administered once a day into a vein over a three-minute time period 15 to 30 minutes before the patient receives radiation treatment.

Precautions

Amifostine can cause a decrease in blood pressure when it is administered. During the 24 hours before receiving amifostine, patients need to drink a lot of liquids. When amifostine is being administered, medical personnel will be monitoring the patient's blood pressure. If the blood pressure drops significantly, the infusion of amifostine will be stopped until blood pressure returns to normal. The doctor will decide if the patient should receive any additional amifostine. Patients who have low blood pressure to begin with or patients who are not drinking a lot of fluids-referred to as being dehydrated-should not receive amifostine.

Patients with a known previous allergic reaction to aminothiol drugs should not receive amifostine.

Patients who may be pregnant, thinking of becoming pregnant, or who have a history of heart problems or strokes should tell their doctor before receiving amifostine.

Side effects

The most common side effect from receiving amifostine is a lowering of blood pressure, which occurs in approximately 62% of patients treated at a dose of 910mg/m². This lowering of blood pressure occurs within the first 15 minutes of administering the drug. Blood pressure is monitored throughout the infusion of amifostine. If the blood pressure drops to certain level then the drug is stopped and restarted only when blood pressure returns to normal.

Nausea and vomiting are common side effects. They occur rapidly and can be severe. Usually, patients are given medicines before receiving amifostine that can help prevent or decrease these side effects. Other side effects include sneezing, hiccups, a warm feeling and redness of the face, sleepiness and dizziness, metallic taste, fever, rash, and chills.

Rare side effects of amifostine are: a lowering of calcium levels in the blood, seizures, allergic reactions which include symptoms of fever, shaking chills, itching, low blood pressure, shortness of breath, and rashes. There have been rare reports of throat swelling, chest tightness, and heart stopping.

All side effects a patient experiences should be reported to their doctor.

Interactions

Amifostine causes a decrease in blood pressure and should be used with caution in patients who take blood pressure lowering medicines or other medications that may lower blood pressure. If patients are taking blood pressure medications, they may be asked to stop taking these medications for 24 hours before receiving amifostine.

Patients should tell their doctors if they have a known allergic reaction to amifostine or any other medications or substances, such as foods and preservatives. Before taking any new medications, including nonprescription medications, vitamins, and herbal medications, patients should notify their doctors.

KEY TERMS

Chemotherapy

Specific drugs used to treat cancer.

Enzyme

A protein in the body that breaks down substances, such as food or medicines, into simpler substances that the body can use.

Food and Drug Administration

A government agency that oversees public safety in relation to drugs and medical devices. The FDA gives approval to pharmaceutical companies for commercial marketing of their products.

Intravenous

To enter the body through a vein.

Radiation therapy

The use of high-energy beams focused to treat cancerous tumors.