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What are targeted therapies?
Many of the newer chemotherapy drugs used to treat cancer are
called targeted
therapies. These drugs act on certain parts of cancer
cells to block the growth and spread of cancer. They work by affecting
the processes that make normal cells become cancer cells and cause
tumors to grow. The goal of targeted therapy is to destroy cancer cells
while causing little or no damage to normal, healthy cells. Targeted
therapies can be used to treat certain types of many different cancers,
including lung, pancreatic, head and neck, liver, colorectal, breast
and kidney cancers. Some examples of targeted therapy are:
- erlotinib (Tarceva®)
- cetuximab (Erbitux®)
- panitumumab (Vectibix®)
- lapatinib (Tykerb®)
- bexarotene (Targretin®)
- sorafenib (Nexavar®)
- sunitinib (Sutent®)
Targeted cancer therapies do not damage bone marrow or blood
cells like most standard chemotherapy (chemo) drugs do. They can be
used alone or along with other drugs. They are most often used with
other cancer treatments, such as radiation or chemo. Targeted therapy
is used this way to boost the effects of the main treatment.
Targeted therapy is still relatively new compared to other
forms of cancer treatment, like surgery, radiation, or chemo. It is
only within the last decade or so that it has proven useful as a form
of cancer treatment. Even though they mainly target the cancer cells,
these drugs are not perfect -- they can cause side effects and
sometimes serious reactions.
Many of the targeted therapy drugs can cause a rash or other
skin changes. These changes are side
effects -- part of a normal body
response to the targeted therapy drug. In this case, they are not signs
of a drug allergy. The skin changes that have been linked to targeted
therapy cancer treatments will be discussed here.
Why do targeted therapies cause skin
changes?
Targeted therapies help stop cancers from getting bigger, but
also cause problems with the skin.
These therapies target the epidermal growth factor receptor
(EGFR) protein. EGFR has been found in larger than normal amounts on
the surface of cancer cells from some types of tumors. EGFR tells the
cancer cells to grow and divide. The problem is that normal skin cells
also have a lot of EGFR. So drugs that target or block EGFR often
affect these cells by turning off the signal for them to grow and
making it harder for them to retain moisture.
Some of the newer drugs target other proteins, such as
vascular endothelial growth factor receptor (VEGFR) and
platelet-derived growth factor receptor (PDGFR). These proteins help
tumors maintain their 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 in the next
section).
What kind of skin changes can targeted
therapies cause?
Rash
The most common skin change is a rash. The risk of getting the
rash and how severe 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 a lot like
acne and shows up on the scalp, face, 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
"whitehead" pimples with pus in the center often appear. The rash can
be itchy. It may improve 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 cause self-esteem
problems. It can also lead to infections, and it may be painful.
Prevention and treatment are key and are discussed in the next 2
sections.
Dry skin
The skin can become very dry and scaly and may even crack
open. This can happen on its own or with the rash. When it happens with
the rash it tends to be worse.
Itching
Many of the skin changes, like rash or dryness, can cause
itching. Steps to prevent and treat skin changes, as discussed below,
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
fingernails)
Some targeted therapies may cause swollen, red, open, and
painful skin sores around the fingernails and toenails. This most often
happens to the big toes and thumbs.
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 and peel, and you may feel
burning, tingling, or numb sensations. HFS can be painful and can
affect your ability to walk and carry out normal activities. If it
becomes severe, pain medicines may be needed. It is important to let
your doctor know if you are having any symptoms of HFS -- even if they
are mild. Treating HFS early can help prevent severe cases. Like the
other skin changes discussed, it can be treated, and there are things
you can do to try to prevent it. These are reviewed in the next
section.
Changes in hair growth
Hair on your head can become thin, dry and brittle, or even
curly. Facial hair for both men and women may grow faster than usual,
including longer, thicker eyelashes that may need to be trimmed. These
changes usually do not happen right away, but you may notice them later
as treatment goes on.
Changes in hair or skin color
Some of the newer drugs can cause the skin or hair to turn a
yellowish color during treatment. This typically goes away once
treatment is finished.
Other side effects
Many other less common side effects have also been linked to
treatment with targeted therapies. These include the following:
- diarrhea
- nausea and vomiting
- constipation
- mouth sores
- shortness of breath
- cough
- feeling tired all the time (fatigue)
- headache
- swelling in your hands and feet
- high blood pressure
Your health care team will watch you closely during treatment
and will check your blood counts often. Side effects can and should be
treated as early as possible. It is important that you tell your health
care team about any changes in how you feel or anything you notice that
is new or unusual. Tell them right away so they can treat any problems
and try to keep them from getting worse.
Can skin changes be prevented?
There are some things you can do 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. Your doctor may suggest you do the following:
- Use a mild soap or body wash that does not contain
alcohol, perfume, or dye.
- Take baths instead of showers, and try oatmeal bath
products to soothe the skin.
- Bathe with cool or lukewarm (instead of hot) water.
- Moisturize your skin 2 times a day with a thick,
alcohol-, perfume-, and dye-free cream. Do this right after bathing
while your skin is still damp.
- Do not use laundry detergents with strong perfumes.
- Stay out of the sun as much as possible.
- If you will be outside, use a sunscreen with SPF of
at least 30 and zinc oxide or titanium dioxide at least 1 to 2 hours
before going out; wear cotton clothing and a hat, too.
- Though the rash may look like acne, do not use acne
treatment medicines on it -- they can dry it out and make it worse.
- Do not wear tight shoes.
- Gel shoe inserts may help if soles of your feet are
tender.
- Some makeup brands, such as Dermablend®,
can cover the rash without making it worse.
Ask your doctor or nurse if there are other specific steps you
can take to help lower the chance of skin problems becoming more
severe.
What should I do if I have skin changes?
It is very important to tell your doctor or nurse about any
rashes or skin changes you notice. Left untreated, the rash can get
worse and lead to infection, as well as the need to hold or even 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 you take
by mouth to treat the skin changes you have. Use theses medicines the
way the doctor tells you to and start them right away. Let your health
care team know if your skin is not getting better after 2 weeks of
treatment.
Be sure to let your doctor or nurse know if:
- 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 itchiness. 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.
Can skin changes be treated?
Mild changes
Patients with mild skin changes may not need any treatment.
This includes rashes that are only in a limited area, not causing any
distress, and not infected. The doctor may prescribe a mild
corticosteroid cream (such as hydrocortisone) or antibiotic gel (such
as clindamycin) to be applied to the area.
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
This includes rash over a larger area of the body or skin
changes causing mild distress from itching or soreness, but with no
signs of infection. Skin treatment may be 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.
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
not.
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 an oral corticosteroid, such as
methylprednisolone (Medrol®) or
prednisone, is often given.
The targeted therapy drug dose is often reduced for these skin
changes. 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 ongoing skin care.
A note about steroid skin creams and gels
Topical steroids (those that are spread on the skin in the
form or creams or gels) can be helpful for many skin problems, and they
can be used for up to 7 days after the problem has gone away. But it is
important to know that long-term use of steroid creams can cause skin
problems, and can make you more likely to get a skin infection. For
this reason, steroid creams should not be used more than 14 days in a
row. Many doctors suggest that patients use topical steroids on a cycle
of every day for 14 days, followed by a 7 day break from treatment.
This cycle can be repeated as long as you have skin problems.
Skin rash as a sign that treatment is
working
There is some thought 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 is 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.
Additional resources
More information from your American Cancer
Society
The following related information may also be helpful to you.
These materials may be ordered from our toll-free number,
1-800-ACS-2345.
No matter who you are, we can help. Contact us anytime, day or
night, for information and support. Call us at 1-800-ACS-2345 or
visit
www.cancer.org.
References
Agha R, Kinahan K, Bennett CL, Lacouture ME. Dermatologic
challenges in cancer patients and survivors. Oncology.
2007;21:1462-1472.
Community Oncology Conference Highlights. Managing toxicities
of EGFR inhibitors. 2008;5:202-203.
Esper P, Gale D, Muehlbauer P. What kind of rash is it?
Deciphering the dermatologic toxicities of biologic and targeted
therapies. Clin J Oncol
Nurs. 2007;11:659-666.
Lynch TJ, Kim ES, Eaby B, Garey J, West DP, Lacouture ME.
Epidermal growth factor receptor inhibitor-associated cutaneous
toxicities: an evolving paradigm in clinical management. Oncologist.
2007; 12:610-621.
Moore SH, O'Connell MJ, Wilkes GM. Optimizing Outcomes for
Metastatic Colorectal Cancer Patients: An APN Roundtable Discussion.
Institute for Medical Education & Research. March 2008.
Last Medical Review: 07/17/2008
Last Revised: 07/17/2008
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