Targeted therapies represent a new type of cancer treatment, in which specific molecules in cancer cells are blocked to slow or stop the growth of cancer. Compared with conventional chemotherapy, these drugs are more specific and cause fewer side effects commonly associated with chemotherapy, such as infections, weakness, and changes to blood counts. However, most patients receiving a targeted therapy develop skin, hair, nail, and/or eye problems.

Causes

The causes of these skin reactions are drugs that block specific molecules in cancer cells. If the drug blocks one molecule, it is called a single-targeted therapy. If the drug blocks more than one molecule, it is called a multitargeted therapy. Specific side effects to the skin, hair, and nails depend on the drug that the patient receives.

One of the largest groups of targeted therapies are those directed against a molecule known as epidermal growth factor receptor (EGFR), such as cetuximab (Erbitux), erlotinib (Tarceva), and panitumumab (Vectibix). Although EGFR fuels the growth of cancer cells, it also plays a role in the normal growth of the skin, hair, and nails. Consequently, rashes and changes to the hair and nails may occur after treatment with these drugs. Drugs with multiple targets include sorafenib (Nexavar) and sunitinib (Sutent).

Overall, these side effects can be managed in most patients so that appearance of the skin, hair, and nails is unaffected or minimally affected, and treatment can continue. It is important to note that the skin side effects associated with these drugs are not an allergic or infectious reaction.

Signs and symptoms of EGFR inhibitors

A rash affecting the face and upper body develops in 45% to 100% of patients taking drugs that target EGFR and usually occurs within the first few weeks of taking these medications. The rash is usually preceded by redness or a warm sensation of the skin on the face that may feel like sunburn. After several days, tender pimples and pus bumps appear, and the surrounding skin feels slightly tender. Rashes tend to be mild to moderate; however, in some cases they are severe and cause significant physical and cosmetic discomfort.

Other symptoms may include the following:

• Pimples and red bumps on the face, neck, and upper chest or back
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• Tenderness in facial skin, with a sunburn-like sensation and itching in pimples
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• Itching of the skin, especially the scalp
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• Tender sores inside the nose, corners of the mouth, or eyes
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• Painful inflammation around nails, especially the thumbs and big toes
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• Nails that become brittle and may loosen from the nail bed
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• Paper-cut-like fissures of the fingertips
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• Hair loss over the entire scalp and decreased hair on legs or arms
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• Increased growth and curling of the eyelashes and eyebrows
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• Increased facial hair growth
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• Easy bruising of the skin
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• Dry, flaky skin
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• Dry, itchy eyes

In addition to the cosmetic appearance of the rash, the skin can become very tender and itchy, interfering with daily activities and sleep. Vigorous scratching can result in breaks that may make the skin more prone to infections. The inflammation around the nails can make grooming, dressing, and other activities painful or difficult.

Signs and symptoms of multitargeted inhibitors (sorafenib, sunitinib)

The hands and feet can be affected by thickened areas in the skin in 20% to 40% of patients receiving multitargeted inhibitors; these skin areas can be very painful and develop blisters. These areas may also become tender, interfering with daily activities, such as walking or holding objects. However, most skin reactions are mild and manageable. Other symptoms include a rash that occurs in 20% to 40% of patients taking this type of medication. Along with redness, the rash is characterized by a sensation of warmth or burning on the face. Hair loss occurs in up to 25% of patients on sorafenib, but tends to be mild. Dry skin is also common and should be treated early to prevent the development of itching.

Management

Although rashes, dry skin, and nail and hair reactions are rarely severe, they can cause significant discomfort, and in some cases, may lead a patient to decide to stop cancer treatment. It is important to inform your doctor as soon as you start feeling or seeing the appearance of side effects. Early and effective treatments for these reactions are available and may be obtained from an oncologist, oncology nurse, dermatologist, or ophthalmologist familiar with these drugs and their side effects. The following suggestions may help with the management of these reactions:

• Before you begin treatment and at the first sign of a reaction, talk with your oncologist or a dermatologist familiar with the drug you are receiving to learn about its side effects. Ask what to do if a rash or other problems appear (such as how to get a prescription filled or the best way to see the doctor).
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• Avoid the sun, and use a sunscreen with a high sun protection factor (SPF). Ideally, the SPF should be at least 30, and the sunscreen should contain titanium dioxide or zinc oxide. It should be applied every two hours or more frequently if sweating or swimming.
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• Remember to use an adequate amount of sunscreen. Apply more than half a teaspoon of sunscreen to each arm, the face and neck, and just over one teaspoon to the chest and abdomen, back, and each leg.
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• Use a broad-brimmed hat if going outside.
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• Use a mild soap in the shower, and avoid soaps with strong scents. Also, avoid laundry detergent with strong perfumes. Shower with lukewarm water, and avoid long, hot showers.
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• Apply a moisturizer within 15 minutes of showering or bathing to dry areas. Use hypoallergenic moisturizers that do not have perfumes or preservatives (such as Vanicream, Vaseline, Aveeno, and Eucerin).
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• At the first sign of a developing a reaction (such as a warm or burning sensation, pimples, nail fissures, or dry skin), tell your doctor or a dermatologist familiar with these reactions.
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• Avoid anti-acne skin products containing alcohol, benzoyl peroxide, or retinoids because they can dry out your skin.
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• Topical medicated creams, such as pimecrolimus (Elidel), tacrolimus (Protopic), clindamycin gel (many brand names) or topical corticosteroids may be effective to relieve symptoms of a mild rash.
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• Antibiotics in the tetracycline family (doxycycline, minocycline), usually administered for two to four weeks in pill form, are an effective therapy for rashes and nail tenderness
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• Whenever there is discharge of pus, it may be beneficial for your doctor to obtain a sample for a culture, to determine the appropriate treatment.
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• When the skin is very dry and flaky, your dermatologist may prescribe a moisturizer containing urea or lactic acid.
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• For the hand-foot skin reaction to sorafenib and sunitinib, use creams containing urea or high potency corticosteroids. Gel insoles may also help. In addition, avoid trauma or excessive weight on hands and feet.

Summary of Targeted Therapies and Common Side Effects

Drug	Target	Types of cancers for which drug may be prescribed	Side effects
Erlotinib (Tarceva) Gefitinib (Iressa) Cetuximab (Erbitux) Panitumumab (Vectibix)	Single targeted (EGFR)	Colorectal, head/neck, lung, pancreatic	Rash on face and upper body Inflammation around fingernails Dry, itchy skin Hair loss on scalp Increased hair on face and eyelashes
Sorafenib (Nexavar) Sunitinib (Sutent)	Multiple	Renal cell cancer (a type of kidney cancer), gastrointestinal stromal tumor, hepatocellular cancer (a type of liver cancer)	Hand foot skin reactions (tender, thickened areas sometimes with blisters on palms and soles) Redness and flaking on scalp and eyebrows Warm, burning sensation on face along with redness Dry, itchy skin Hair loss on scalp

More Information

Cancer.Net: Managing Side Effects

Cancer.Net Feature: Understanding Targeted Treatments

Last Updated: April 16, 2007