Targeted Therapy

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Side effects of targeted therapy drugs

What causes side effects?

Although targeted therapy drugs don’t affect the body the same way that standard chemo drugs do, they still cause side effects. Side effects from these drugs depend largely on what the drug targets. Some drugs target substances that are more common on cancer cells, but are also found on healthy cells. So these drugs may affect healthy cells, too, causing some side effects.

When drugs attack more than one target, side effects are more likely. Also, drugs that act as angiogenesis inhibitors affect new blood vessel formation all over the body, not just those near the cancer. This can lead to side effects, as well.

What should I know about side effects?

  • Every person doesn’t get every side effect. Some people get few, if any.
  • The severity of side effects varies greatly from person to person. Be sure to talk to your doctor and nurse about which side effects are most likely with your treatment, how long they might last, how bad they might be, and when you should call the doctor’s office about them.
  • Although side effects can be unpleasant, they must be measured against the need to fight the cancer.
  • Your doctor may give you medicines to prevent some side effects before they happen or to treat certain side effects once they occur.
  • Rare and unusual side effects may happen with some of these drugs, and some may be serious. All changes and side effects should be reported to your doctor.
  • Many people have no long-term problems from targeted therapy drugs.

How long do side effects last?

Most side effects slowly go away after treatment ends and the healthy cells recover. The time it takes to get over some side effects and regain energy varies from person to person. It depends on many factors, including your overall health and the drugs you were given.

Because many targeted therapy drugs are still quite new, it’s hard to say how long you can expect side effects to last. We do know that some of the side effects from standard chemo drugs can last a lifetime, such as when the drug causes long-term damage to the heart, lungs, kidneys, or reproductive organs. We still don’t know if targeted therapy drugs cause these kinds of long-term changes.

Patients often become discouraged about how long their treatment lasts or the side effects they have. If you feel this way, talk to your doctor. You may be able to change your medicine or treatment schedule. Your doctor or nurse may be able to suggest ways to reduce problems or discomfort.

What are common side effects?

You are not alone if you have questions about side effects. Before cancer treatment starts, most people worry about whether they will have side effects and, if so, what they will be like. Here’s a review of some of the most common side effects caused by targeted therapy drugs. We also share some tips on how to manage them.

Skin problems

Many of the targeted therapy drugs can cause a rash or other skin changes. In fact, more than half the people taking certain drugs have some skin effects. These problems usually develop slowly over days to weeks and are not signs of a drug allergy.

In contrast, allergic reactions to drugs tend to start suddenly, usually within minutes to hours after taking the drug. They may include hives (raised skin welts that often go away within a day or so), and intense itching. An allergic reaction often includes other serious symptoms such as trouble breathing, dizziness, tightness in the throat or chest, or swelling of the lips or tongue. If you have these kinds of symptoms, get emergency help and call your doctor right away.

Why do targeted therapies cause skin changes?

Some targeted therapy drugs target the epidermal growth factor receptor (EGFR) protein, which tells the cancer cells to grow and divide. The problem is that normal skin cells also have a lot of EGFR, and they must grow quickly to maintain the skin’s surface layer. Drugs that target or block EGFR often affect skin cells, too. They turn off the signal for skin cells to grow normally and make it harder for them to retain moisture.

Some drugs target other proteins, such as vascular endothelial growth factor (VEGF). These proteins help tumors build and keep a blood supply, but they also seem to be important to the very small blood vessels in the hands and feet. Damage to these tiny blood vessels can cause hand-foot syndrome (described later).

Researchers have noticed that people who are getting radiation therapy at the same time they get targeted drugs often have worse skin problems in the area that receives radiation.

What kind of skin changes can targeted therapies cause?

Changes in how your skin feels: Your skin may start off feeling like it’s sunburned, before any redness or rash shows up. Even though it doesn’t look different, the sensation can be disturbing. You may notice this change on your face as early as the first week of treatment.

Rash: The most common skin change is a rash. The risk of getting the rash and how bad it is depends on the type of cancer and the type and dose of the targeted therapy drug used to treat it. The rash is mild for most people. It often looks like acne (but with no blackheads) and shows up on the scalp, face, neck, chest, and upper back. In severe cases it can affect other parts of the body.

The rash most often starts as skin redness and swelling and is often worst within the first few weeks of treatment. By about the 4th week of treatment, the skin usually crusts and gets very dry and red. In the weeks after that, round, flat or raised red spots and pimples with pus in the center often appear. The rash can itch, burn, or sting, and may feel tender (painful) when you touch it. It may get better or stay about the same during the rest of treatment, but it should completely go away about a month after treatment is stopped.

The rash can be very distressing and make a person feel self-conscious around others. It might be painful and can lead to infections. Prevention and treatment are discussed later.

Dry skin: The skin can become very dry and scaly and may even crack open. Cracking can happen by itself or come with the rash. Cracking tends to be worse when it happens with the rash.

Itching: Many of the skin changes, like rash or dryness, can cause itching. Steps to prevent and treat skin changes, as discussed later, can help with itching. Some people may need to take medicine by mouth, such as diphenhydramine (Benadryl®), to get relief.

Red, sore cuticles (the areas around the nails): Some targeted therapies cause swollen, red, open, and painful skin sores around the fingernails and toenails. (This can look a lot like an infection or an ingrown nail.) This most often happens to the big toes and thumbs. These sores may become infected. Nails may also become brittle and grow more slowly.

Hand-foot syndrome: Hand-foot syndrome (HFS) has been linked to many cancer treatment drugs, including some targeted therapies. The cause of this syndrome is not known for sure. It may have to do with damage to the tiny blood vessels in the hands and feet, or with the drugs themselves leaking out of the blood vessels and causing tissue damage.

A painful sensitivity of the hands and feet is the earliest symptom of HFS. Then, redness and swelling start in the palms of the hands and the soles of the feet. This redness looks a lot like sunburn and may blister. In severe cases, the blisters can open up and become sores. The affected skin also can become dry, peel, and crack. It may burn, tingle, or feel numb.

HFS can be painful and can affect your ability to walk and do your normal activities. If it becomes severe, pain medicines may be needed. Let your doctor know if you are having HFS symptoms—even if they are mild. Treating HFS early can help keep it from getting worse. Like the other skin changes discussed, it can be treated, and there are things you can do to try to prevent it.

Changes in hair growth: Hair on your head can become thin, dry and brittle, or even curly. Long-term use of targeted therapy may lead to bald patches or complete loss of scalp hair. Facial hair for both men and women may grow faster than usual, including longer, thicker, curly eyebrows and eyelashes that may need to be trimmed. But in some men, facial hair growth slows down. Eyebrows may thin out as well. These changes usually don’t happen right away, but you may notice them later as treatment goes on.

Some people notice sores on the scalp and other hairy areas. Scars caused by these sores may keep your hair from growing back after treatment is finished.

Changes in hair or skin color: Some of these drugs can cause the skin or hair to turn a yellowish color during treatment. In a few people, hair becomes darker. This tends to go away once treatment ends.

Changes in and around the eyes: The eye itself may burn, and become dry or red. In some, the eyelids get tender, swollen, or inflamed, and crusts may be seen in the lashes. In a few people the eyelids may turn inward or outward. Distorted eyelids or prolonged dryness can damage the clear part of the eye (the cornea). Talk with your doctor or nurse about managing these changes to avoid injury, pain, or infection.

Can skin changes be prevented?

You can do some things to help prevent skin changes or at least to try to keep them under control. You should start to do them as soon as targeted therapy treatment begins—before any problems start. Starting good skin care before side effects begin may help to keep the problems to a minimum. Your doctor may ask you to do the following:

  • Use a mild soap or body wash and shampoo that do not contain alcohol, perfume, or dye.
  • Take baths instead of showers, and try oatmeal bath products to soothe your skin.
  • Bathe with cool or lukewarm (instead of hot) water. Avoid hot, humid places.
  • Moisturize your skin at least 2 times a day with a thick cream that contains no alcohol, perfume, or dye. Right after you bathe, while your skin is still damp, is the best time to do this.
  • Do not use laundry detergents or fabric softeners with strong perfumes.
  • Stay out of the sun. Wear hats, long sleeves, and sunscreen if you are outside during the day. Sunlight seems to trigger the rash in some people.
  • Use a broad-spectrum sunscreen with SPF of at least 30 and zinc oxide or titanium dioxide at least 1 to 2 hours before going out, if you will be outside during the day. Wear cotton clothes and a hat, too.
  • Though the rash may look like acne, acne medicines do not work on it—they can dry it out and make it worse.
  • If the soles of your feet are tender, gel shoe inserts may help.
  • Wear shoes that fit well and aren’t too tight. Thick, soft socks may help if you have shoes that are big enough for the extra bulk.
  • Some makeup brands, such as Dermablend®, can cover the rash without making it worse.

One study that looked at using Vitamin K cream twice a day suggested it might reduce the severity of the skin rashes, but this is still being researched. Ask your doctor or nurse if there are other things you can do to help lower the chance of skin problems getting worse.

What should I do if I have skin changes?

It’s very important to tell your doctor or nurse right away about any rashes or skin changes you notice. Left untreated, rashes can get worse and lead to infection, which can delay or even cause your doctor to stop treatment. Do not treat your skin with over-the-counter medicines or stop taking your targeted therapy without talking to your doctor first.

Your doctor may give you a skin cream or a medicine to take by mouth to treat the skin changes you have. Use these medicines the way the doctor tells you to and start them right away. Let your health care team know if your skin gets worse, or is not getting better after 2 weeks of treatment.

Be sure to let your doctor or nurse know if:

  • You notice a burning feeling, redness, or rash. There are creams you can use to try to keep it from getting worse.
  • Your skin is dry, flaking, or cracked. Moisturizing cream may help with this.
  • Your skin is itchy. There are creams and gels you can use to ease itching. There are also some medicines you can take by mouth to try to stop the itching.
  • The area around your fingernails or toenails becomes sore or red. Creams and soaks can help with this. But you and your health care team will need to watch for changes that could be signs of infection to be sure any infection is treated quickly.
  • You have very dry, red, or tender eyes, or if you notice eyelashes growing inward toward the eyeball.
  • You get sores on your scalp or other areas with hair. You will want to get them treated to help prevent scars that may block hair growth later.

Try to avoid exposure to sunlight. Even after treatment is over, you may find that you are more sensitive to the sun’s rays than before.

Can skin changes be treated?

Because these skin problems are linked to newer drugs, the best ways to handle them are still being studied. But doctors can help you manage them using what’s already known about these kinds of changes.

The doctor will need to check your skin fairly often to figure out the problem, the best course of action, and whether treatment is helping. You will probably need extra doctor visits while the problem is being brought under control.

Mild changes: Patients with mild skin changes may not need any treatment. These changes include rashes that are only in a limited area, that are not causing any distress, and are not infected. Heavy skin creams or ointments that contain no alcohol, perfume, or dye can sometimes help with dryness. Be sure to talk with your nurse or doctor before using anything on your skin.

The doctor also may prescribe a mild corticosteroid cream (such as hydrocortisone) or antibiotic gel (such as clindamycin) to put on the rash. Careful cleansing and clean, warm, wet cloths laid over your closed eyes may help if your eyelids are crusty or swollen.

The dose of the targeted therapy drug is usually not changed, and the patient is closely watched to see if the rash gets better or worse.

Moderate changes: These include a rash over a larger area of the body or skin changes causing mild distress from itching or soreness, but with no signs of infection. The skin may be treated with hydrocortisone cream, clindamycin gel, or pimecrolimus (Elidel®) cream. The doctor may also prescribe an antibiotic such as doxycycline or minocycline to be taken by mouth. Drops or ointments may be prescribed to help with eye problems.

The dose of the targeted therapy drug is usually not changed, and the patient is closely watched to see if the rash gets better or worse.

Severe changes: These are bad rashes that cover a lot of skin, cause itching and soreness that affect the patient’s quality of life (such as sleep problems or pain), and are likely to get infected. Treatment is much like that used for moderate changes, including a topical cream or gel (hydrocortisone cream, clindamycin gel, or pimecrolimus cream), as well as an antibiotic such as doxycycline or minocycline that is taken by mouth. Along with this, a course of corticosteroid pills, such as methylprednisolone (Medrol®) or prednisone, is often given.

The targeted therapy drug dose is often reduced when a person has severe skin changes. Expect to see your doctor often during this time. If the rash does not get better in 2 weeks, the targeted drug is often stopped until the skin changes improve. It may then be re-started with continued skin care.

A note about steroid skin creams and gels

Steroids that are spread on the skin in the form of creams, ointments, or gels can help many skin problems. They can be used for up to 7 days after the problem has gone away. But it’s important to know that using steroid creams for too long can actually cause skin problems, and can make you more likely to get a skin infection. For this reason, steroid creams (even those that don’t require a prescription) should not be used more than 14 days in a row unless your doctor tells you to. Many doctors suggest that patients who are given steroids to put on their skin use it in cycles. For instance, you might use it every day for 14 days, and then stop using it for a 7-day break. This cycle can be repeated as long as you have skin problems, or until your doctor tells you to stop.

Skin rash as a sign that treatment is working

Some people believe that the skin rash may be a sign that the targeted therapy is working (the worse the rash, the better the treatment is working). But long-term follow-up is needed to link the rash to outcomes. People with no rash or with only a mild rash should not assume that the treatment is not working.

The 2 most important things you can do are to take good care of your skin when you start targeted therapy and let your doctor know right away about any skin changes you may have.

High blood pressure

Some targeted therapy drugs can raise your blood pressure. There isn’t really anything you can do to prevent this, but your doctor will watch your blood pressure closely if you are on a drug with this side effect. Some people need medicine to bring their blood pressure down to a safe level while being treated with targeted therapy. They should stay on this medicine until their doctor tells them it can be stopped.

Problems with bleeding or clotting

Angiogenesis inhibitors interfere with the formation of new blood vessels. This can lead to problems with bruising and bleeding. Bleeding, such as from the stomach and intestines, can be severe and even cause death. Tell your doctor if you throw up blood or material that looks like coffee grounds, or if you notice blood in your stool. These can be signs of bleeding in the stomach or intestines.

These drugs can also cause clots in the lungs and legs, as well as heart attacks and strokes. Let your doctor know if you have problems with sudden swelling, pain, or tenderness in the arm or leg. If you have chest pain, sudden shortness of breath, vision problems, weakness, seizures, or trouble speaking, get emergency help. These can be symptoms of serious conditions caused by blood clots.

These problems are rare, and there is no way to prevent them. If you have a problem like this, you may need to stop taking the targeted therapy drug.

Problems with wound healing

By blocking the formation of new blood vessels, angiogenesis inhibitors also interfere with wound healing. This can lead to old wounds (cuts) opening up again and new wounds not closing. It can also lead to holes opening up in the stomach or intestine (these are called perforations). Tell your doctor right away if you have pain in your belly or vomiting.

Because these drugs interfere with wound healing, they are usually stopped before any planned surgery.

Other side effects

Other less common side effects have also been linked to treatment with targeted therapies. These include:

  • Diarrhea
  • Nausea and vomiting
  • Constipation
  • Mouth sores
  • Shortness of breath or trouble breathing
  • Cough
  • Feeling tired all the time (fatigue)
  • Headache
  • Swelling in your hands and feet
  • Low blood cell counts

Keep in mind that these are not all of the side effects that people have had, just some of the more common ones. Some of these drugs also affect the heart and interact with other drugs and even foods. Each drug has different effects. To find out more about the drug you are taking call us or see our online Guide to Cancer Drugs.

Your health care team will watch you closely during treatment and will check you often. Side effects can and should be treated as early as possible. It’s important that you tell your health care team about any changes in how you feel or anything you notice that’s new or unusual. Tell them right away so they can treat any problems and try to keep them from getting worse.

You can learn more about managing these side effects and cancer treatment in general in our booklet called A Guide to Chemotherapy.

Last Medical Review: 07/12/2013
Last Revised: 07/12/2013