Denileukin Diftitox (Ontak®)

Last Modified: August 21, 2011

Pronounced: DEN-i-LOO-kin DIF-ti-tox
Classification: Biologic Response Modifier

About Denileukin Diftitox

Denileukin diftitox is a type of medication called a "biologic response modifier". It is designed to target the CD25 component of the IL-2 receptor, which is found on the malignant cells of patients with certain cancers. When bound to the receptor, the drug inhibits synthesis of certain proteins, and thus causes cell death. The medication only works in tumors that have the CD25 receptor, so testing should be done for this before starting the medication.

How to Take Denileukin Diftitox

Denileukin diftitox is given through intravenous (into a vein) infusion, over a period of 30-60 minutes, but can take longer depending on the patient's reaction to the infusion. It is given for 5 consecutive days, every 21 days. The actual dose is dependent on your body size. Premedication with acetaminophen (Tylenol) and diphenhydramine (Benadryl) will be given to lower the risk of infusion reactions.

Possible Side Effects of Denileukin Diftitox

There are a number of things you can do to manage the side effects of Denileukin Diftitox. Talk to your doctor or nurse about these recommendations. They can help you decide what will work best for you. These are some of the most common side effects:

Infusion-Related Side Effects

The denileukin diftitox infusion can cause a reaction that may include low blood pressure, back pain, shortness of breath, rash, and chest pain. The infusion may be stopped or slowed down if this occurs, and steroids (hydrocortisone or decadron), diphenhydramine, and epinephrine may be given to stop the reaction. These reactions generally occur within 24 hours of the dose, and most often occur during the first and second cycles.

Flu-Like Syndrome

This occurs in more than 90% of patients. Flu-like syndrome occurs hours to days after the infusion and is characterized by fever, chills, weakness, nausea, vomiting, and muscle and joint aches. Medications such as acetaminophen and anti-nausea medications can be used to manage these symptoms.


Your oncology team can recommend medications to relieve diarrhea. Also, try eating low-fiber, bland foods, such as white rice and boiled or baked chicken. Avoid raw fruits, vegetables, whole grain breads, cereals and seeds. Soluble fiber is found in some foods that absorbs fluid and can help relieve diarrhea. Foods high in soluble fiber include: applesauce, bananas (ripe), canned fruit, orange and grapefruit sections, boiled potatoes, white rice and products made with white flour, oatmeal, cream of rice, cream of wheat, and farina. Drink 8-10 glasses on non-alcoholic, un-caffeinated fluid a day to prevent dehydration. Read Low Fiber Diet for Diarrhea for more tips.


Rash with or without itching may occur. Antihistamines (like diphenhydramine) or topical steroids can be used to control symptoms. It is important to prevent scratching and breaking of the skin, given the already high risk for skin infections in patient with CTCL, now at even higher risk on this therapy. Some patients also reported tingling or burning of the skin.

Low White Blood Cell Count (Leukopenia or Neutropenia)

White blood cells (WBC) are important for fighting infection. While receiving treatment, your WBC count can drop, putting you at a higher risk of getting an infection. You should let your doctor or nurse know right away if you have a fever (temperature greater than 100.4 F), sore throat or cold, shortness of breath, cough, burning with urination, or a sore that doesn't heal.

Tips to preventing infection:

  • Washing hands, both yours and your visitors, is the best way to prevent the spread of infection.
  • Avoid large crowds and people who are sick (i.e.: those who have a cold, fever or cough or live with someone with these symptoms).
  • When working in your yard, wear protective clothing including long pants and gloves.
  • Do not handle pet waste.
  • Keep all cuts or scratches clean.
  • Shower or bath daily and perform frequent mouth care.
  • Do not cut cuticles or ingrown nails. You may wear nail polish, but not fake nails.
  • Ask your doctor or nurse before scheduling dental appointments or procedures.
  • Ask your doctor or nurse before you, or someone you live with, has any vaccinations.

For more suggestions, read the Neutropenia Tip Sheet.

Low Red Blood Cell Count (Anemia)

Your red blood cells are responsible for carrying oxygen to the tissues in your body. When the red cell count is low, you may feel tired or weak. You should let your doctor or nurse know if you experience any shortness of breath, difficulty breathing or pain in your chest. If the count gets too low, you may receive a blood transfusion. Read the anemia tip sheet for more information.

Nausea and/or Vomiting

Take anti-nausea medications as prescribed. If you continue to have nausea or vomiting, notify your doctor or nurse so they can help you manage this side effect. In addition, dietary changes may help. Avoid things that may worsen the symptoms, such as heavy or greasy/fatty, spicy or acidic foods (lemons, tomatoes, oranges). Try antacids, (e.g. milk of magnesia, calcium tablets such as Tums), saltines, or ginger ale to lessen symptoms. Read the Nausea & Vomiting Tip Sheet for more suggestions.

Call your doctor or nurse if you are unable to keep fluids down for more than 12 hours or if you feel lightheaded or dizzy at any time.

Capillary Leak Syndrome

Capillary leak syndrome is a potentially serious complication in which fluids from the veins and capillaries leak into the tissue outside the bloodstream. This results in low blood pressure and poor blood flow to the internal organs. Capillary leak syndrome is characterized by the presence of 2 or more of the following 3 symptoms: low blood pressure, swelling, and low levels of protein in the blood (hypoalbuminemia). Your doctor will monitor these levels while you are taking denileukin diftitox. You should notify your doctor immediately if you notice dizziness (especially when changing position), sudden swelling or rapid weight gain, little or no urine output (for 8-12 hours), shortness of breath, difficulty breathing, irregular heart beats, or chest pain. This syndrome generally occurs within about 2 weeks of treatment.


While on cancer treatment you may need to adjust your schedule to manage fatigue. Plan times to rest during the day and conserve energy for more important activities. Exercise can help combat fatigue; a simple daily walk with a friend can help. Talk to your healthcare team and see OncoLink's section on fatigue for helpful tips on dealing with this side effect.

Decrease in Appetite

Visit OncoLink's section on Nutrition for tips on dealing with this side effect. Ask your nurse about nutritional counseling services.

  • Try to eat five or six small meals or snacks throughout the day, instead of 3 larger meals.
  • If you are not eating enough, nutritional supplements may help.
  • You may experience a metallic taste or dislike foods or beverages that you liked before receiving chemotherapy. These symptoms can last up to several months.
  • Avoid any food that you think smells or tastes bad. If red meat is a problem, eat chicken, turkey, eggs, dairy products and fish without a strong smell.
  • Flavor meat or fish by marinating it in sweet juices, sweet and sour sauce or dressings. Use seasonings like basil, oregano or rosemary. Bacon, ham and onion can also add flavor to vegetables.


Patients in clinical trials reported blurry vision and/or a loss of color vision. While this resolved in some patients, visual changes were persistent in most patients.


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