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What is photodynamic therapy (PDT)?
Photodynamic therapy (PDT) is a treatment that uses drugs,
called photosensitizing
agents, along with light to kill cancer cells. The drugs
only work after they have been activated or "turned on" by certain
kinds of light. PDT is also called photoradiation
therapy, phototherapy,
or photochemotherapy.
It was first used to treat cancer over 100 years ago.
Depending on the part of the body being treated, the
photosensitizing agent is either injected into the bloodstream or put
on the skin. Over a certain amount of time the drug is absorbed by the
cancer cells. Then light is applied to the area to be treated. The
light causes the drug to react with oxygen, which forms a chemical that
kills the cancer cells. PDT may also work by destroying the blood
vessels that feed the cancer cells and by alerting the immune system to
attack the cancer.
The period of time between when the drug is given and when the
light is applied is called the drug-to-light interval. It can be
anywhere from a couple of hours to a couple of days and depends on the
drug used.
Pros and cons of PDT
Studies have shown that PDT can work as well as surgery or
radiation therapy in treating certain kinds of cancers and pre-cancers.
It may have some advantages, such as:
- It has no long-term side effects when used properly.
- It is less invasive than surgery.
- It can be targeted very precisely.
- Unlike radiation, PDT can be repeated many times at the
same site if needed.
- There is little or no scarring after the site heals.
But PDT has limits, too. It can only treat areas where light
can reach, so it is mainly used to treat problems on or just under the
skin, or in the lining of internal organs. The drugs may travel
throughout the body, but the treatment only works at the area exposed
to light. This is why PDT can't be used to treat cancers that have
spread to many places. Also, the drugs that are used now leave people
very sensitive to light, so special precautions must be taken during
this time.
PDT cannot be used in people who have a blood disease called acute intermittent porphyria
or people who are allergic to porphyrins.
What types of cancer is PDT used for?
PDT has been used in people with cancer to help them live
longer and improve their quality of life. Although PDT works and causes
no long-term problems, it is not widely used to treat cancer today.
Still, it is offered in some treatment centers, and is being studied in
many clinical trials. It is becoming more widely recognized as a
valuable treatment option for localized cancers (cancers that have not
spread far from where they started). Three photosensitizing agents are
currently approved by the United States Food and Drug Administration
(FDA) to treat certain cancers or pre-cancers, they are reviewed in the
next section.
What PDT drugs have been approved?
Porfimer sodium (Photofrin®)
Porfimer sodium is the most widely used and studied
photosensitizer. It is activated by red light from a laser to treat
patients with:
- cancer of the esophagus (the swallowing tube)
- to relieve symptoms that are caused by a tumor totally
blocking the esophagus
- to relieve symptoms that are caused by a tumor that partly
blocks the esophagus and can't be treated with laser therapy
- Barrett esophagus, a condition that may lead to
esophageal cancer in patients who don't have surgery
- a type of non-small cell lung cancer that affects
the lining of the bronchi (endobronchial) and has minimal spread of
cancer cells (micro-invasive). It is used in patients who can't have
other types of treatment, such as surgery or radiation therapy. PDT can
help to shrink tumors that are blocking the airway.
- certain skin cancers, such as basal cell carcinoma
and squamous cell carcinoma, the most common skin cancers. It is also
used for Bowen disease and nevoid basal cell carcinoma syndrome (NBCC)
- some tumors of the vagina, vulva, and cervix that
can be reached by the activating light
Aminolevulinic acid (ALA or
Levulan®)
Aminolevulinic acid is a drug that is put directly on the
skin. It is used to treat actinic keratosis (AK), a skin condition that
can become cancer, and mycosis fungoides, a skin lymphoma. It is
approved for use only on the face or scalp. A special blue light,
rather than laser light, is used to activate this drug.
Methyl ester of ALA (Metvixia®
Cream)
Methyl ester of ALA is one of several other forms of ALA that
have been developed. A disadvantage of the older forms of ALA is that
they do not get into the cancer cells very easily. Newer ester forms,
like this one, do. It was approved by the FDA in July 2004 for
treatment of non-hyperkeratotic actinic keratoses of the face and
scalp. Again, these are skin conditions that can become cancer. Methyl
ester of ALA is activated with a red light.
Verteporfin (Visudyne®)
Verteporfin has been developed and used to treat age-related
macular degeneration, a progressive eye problem that leads to
blindness. While it is a PDT, it is not used in cancer treatment and is
not discussed in detail here.
What about newer PTD drugs?
Researchers are still looking for new photodynamic therapy
drugs, and many are being studied in clinical trials. Photodynamic
therapy is now being tested for use against several other types of
cancer, too. See "The
future of photodynamic therapy" section below.
PDT using porfimer sodium
What is treatment like?
First, the porfimer sodium is given intravenously (IV or into
a vein). It travels through the bloodstream to be absorbed by all cells
in the body, including both normal and cancer cells. The normal cells
get rid of most of the porfimer sodium over a couple of days. But a lot
of the drug stays in the cancer cells and in the skin cells.
Porfimer sodium alone does not destroy cancer cells. It must
be activated or turned on with light. This is done about 2 or 3 days
after the drug is given. (This gives the normal cells a chance to get
rid of the drug.) The doctor then directs a laser light at the area of
cancer cells using a very thin
fiber optic glass strand. To treat
esophageal cancer or Barrett esophagus, the fiber optic is passed down
the throat through a thin, flexible tube called an endoscope. For lung
cancer treatment, the fiber optic is passed through a bronchoscope,
which is an endoscope that is designed to reach the lung.
The laser used is a low-power light so it does not burn. It
causes little or no pain. The light is applied for 5 to 40 minutes,
depending on the size of the tumor being treated. Any dead tissue left
in the treated area is removed about 4 or 5 days later during endoscopy
or bronchoscopy. The treatment can be repeated if needed.
Who should not get treated with porfimer
sodium?
Porfimer sodium is not recommended for people with:
- a fistula (abnormal opening) between the windpipe
and esophagus or between a bronchus and esophagus
- a tumor that is spreading into a major blood vessel
Possible side effects
The major possible side effects from porfimer sodium are
photosensitivity reactions (reactions triggered by light) and swelling
in the treated area. Swelling may cause pain or trouble swallowing or
breathing. Other minor side effects are possible, too.
Photosensitivity reactions
As soon as porfimer sodium is put into the bloodstream, it
begins to collect in the cells of the body. Some of it will stay in the
cells for several weeks. The skin and eyes become very sensitive to
light during this time. If exposed to sunlight or other forms of bright
light, the skin can quickly become swollen, sunburned, and blistered.
It takes only a few minutes for a reaction to occur, so it is very
important to protect the eyes and skin during this time. After you get
an injection of porfimer sodium, you should take precautions (see
below) for at least 30 days to prevent reactions. Sensitivity to light
can last as long as 3 months, but the length of time is different with
each person. If you have a reaction, call your doctor right away.
You should try to avoid bright lights and direct sunlight, but
you do not have stay in dark rooms. Some indoor light is important
because it will help to slowly break down the drug in your skin. As
this happens, your skin will become less sensitive to light over time.
Ask your doctor when and how you should test your skin for
photosensitivity. This is usually done no sooner than 30 days after you
get the drug.
You can help prevent a photosensitivity reaction if you
prepare before the treatment and use precautions after:
- Before going to your doctor's office or hospital
for treatment, close the shades and curtains on the windows in your
home. Be sure windows and skylights are fully covered.
- Bring dark sunglasses, gloves, a wide brimmed hat,
long pants, socks, shoes, and a long-sleeve shirt to wear after your
appointment. Clothing should be light in color and the fabric should be
tightly woven.
- Do not count on sunscreen to protect you. Most
sunscreens only protect against ultraviolet light, and they will not
prevent a photosensitivity reaction.
- For at least 30 days after you get the injection,
limit your time outdoors, especially when the sun's rays are strongest
(between about 10AM and 4PM). When you do go outside, cover as much
skin as possible, even on cloudy days and when you are in the car.
- Try to do most daily errands after sundown.
- Do not expose your skin to reading lamps, exam
lamps (like those used in a dentist's office), or "helmet"-type hair
dryers (such as those found in beauty salons). If you use a hand-held
hair dryer, use a low heat setting to avoid burns to your scalp.
Swelling
Swelling in the area being treated can lead to pain in the
chest or back. If the esophagus is being treated, it may lead to
narrowing (stricture) of the esophagus, which could cause problems
swallowing. Treatment of the lung could lead to trouble breathing. If
you notice any of these problems, let your doctor know right away.
Other possible side effects
Side effects depend on the part of the body being treated. If
the esophagus is being treated, possible side effects include nausea,
vomiting, fever, dehydration, headache, and hiccups. In people being
treated for lung cancer, possible side effects include shortness of
breath, coughing up blood, fever, pneumonia, and bronchitis.
If you are being treated with porfimer sodium, ask your doctor
which side effects to report right away and what phone number to call
if you have side effects after regular office hours.
PDT using aminolevulinic acid (ALA)
What is treatment like?
Aminolevulinic acid (Levulan®
Kerastick) is a solution
that is applied directly to the lesions or spots on the face or scalp
to treat actinic keratosis lesions. Unlike porfimer sodium, it does not
reach other parts of the body. This is why the lesions are sensitive to
the light but the rest of the body is not.
About 14 to 18 hours after the drug is applied (usually the
next day), your doctor will expose the area being treated to a blue
light source for about 15 minutes. During the light therapy you and the
doctor will wear protective eyewear. You may feel stinging or burning
once the area is exposed to the blue light, but it should go away
within a day. The treated areas may get red and scale and crust for up
to 4 weeks before healing. If a lesion does not completely go away
after treatment, the area can be treated again 8 weeks later.
Who should not get treated with
aminolevulinic acid?
Aminolevulinic acid is NOT recommended for people with:
- skin sensitivity to blue light
Possible side effects
Photosensitivity reactions
Reactions caused by light can show up on the skin where the
drug is applied. They usually involve redness and a tingling or burning
sensation. For about 2 days after the drug is used, you should take
care to not expose the face and scalp area to light:
- Stay out of strong, direct light.
- Stay indoors as much as possible.
- Wear protective clothing and wide-brimmed hats to
avoid sunlight when outdoors.
- Avoid beaches, snow, light colored concrete, or
other surfaces where strong light may be reflected.
Sunscreens will not protect the skin from photosensitivity
reactions.
Skin changes
The skin being treated will likely turn red and may swell
after treatment. This usually peaks about a day after treatment, gets
better within a week, and should be gone by 4 weeks after treatment.
The skin may also be itchy or change color after treatment.
Talk to your doctor about what you should expect your treated
skin to look and feel like. Also ask about which side effects you
should report right away and what phone number to call if you have
problems after regular office hours.
PDT using methyl ester of ALA
What is treatment like?
Methyl ester of ALA is used very much like aminolevulinic
acid. It is a cream that is put on the skin of the face or scalp to
treat actinic keratosis lesions. The doctor will likely first scrape
the area with a small, sharp blade. This drug does not reach other
parts of the body. The lesions where the cream is applied are sensitive
to light, but the rest of the body is not. The cream should not be left
on the skin for more than 4 hours.
The cream is applied and covered with a bandage. About 3 hours
later your doctor will take off the bandage, wash off the cream, and
expose the area being treated to a red light source for 5 to 20
minutes. During the light therapy you and the doctor will wear
protective goggles. You may feel stinging or burning when the area is
exposed to the light. Two treatment sessions are usually done 7 days
apart. The treated area may turn red, blister, scale, and crust for up
to 10 days before healing. The doctor will look at the lesion about 3
months after the last treatment to see whether it worked.
Who should not get treated with methyl ester
of ALA?
Methyl ester of ALA is NOT recommended for those with:
- skin sensitivity to light
- allergies to peanuts or almonds (these oils are
used to make the cream)
- immunosuppression
Methyl ester of ALA cream has not been studied for more than 2
treatment sessions. Information regarding more treatments done after 3
months for remaining or new AK lesions is not available.
Possible side effects
Photosensitivity reactions
These are reactions triggered by light. They can happen at the
area where the drug was applied, and usually involve redness and a
stinging or burning sensation. You should stay out of the sun, away
from bright indoor lights, and avoid extreme cold after the cream is
applied and before the light treatment is done. For about 2 days after
the light treatment, you should take care to keep the treated area away
from any light.
- Stay out of strong, direct, bright indoor light.
- Stay indoors as much as possible.
- When outdoors, wearing protective clothing and
wide-brimmed hats to avoid sunlight.
- Avoid beaches, snow, light colored concrete, or
other surfaces where strong light may be reflected.
Sunscreens will not protect the skin from photosensitivity.
Skin changes
The skin being treated will likely turn red and may blister
and swell after treatment. Burning and stinging are common. The skin
may also be itchy, scaly, or change color after treatment. These side
effects should get better with time and should be gone by 3 weeks after
treatment. If they get worse or are not gone in 3 weeks, call your
doctor. Ask what other side effects should be reported to the doctor
and what phone number you should use if you have problems after regular
office hours.
The
future of photodynamic therapy
Photodynamic therapy may be used to treat other cancers and
diseases in the future. Current studies are testing the use of PDT for
several types of cancer and pre-cancerous conditions, including cancers
of the:
- skin
- cervix
- bladder
- prostate
- bile duct
- pancreas
- stomach
- brain
- head and neck
New and better drugs
Newer photosensitizing drugs now being studied may have
advantages over the ones now being used:
- They may be able to treat tumors that are deeper
under the skin or in body tissues.
- They may be more selective for cancer cells as
opposed to normal cells.
- They may collect in cancer cells more quickly,
reducing the time needed between getting the drug and doing the light
treatment.
- They may be removed from the body more quickly,
reducing the time people need to worry about photosensitivity
reactions.
An example of one of these new drugs, Photochlor®,
is
now being used in clinical trials. Photochlor or HPPH
(2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide-a) is a
second-generation photosensitizer. It is being studied in the treatment
of tumors that block the esophagus, early stage esophageal cancer, lung
cancer, skin cancer, mouth and throat cancer, and locally recurring
breast cancer on the chest wall after mastectomy. So far, studies have
shown that photosensitivity lasts a much shorter time, and the drug is
removed from the body much faster than Photofrin.
Other light sources
Researchers are also looking at different types of lasers and
other light sources. Some newer agents may respond to small doses of
radiation as well as to light. This could allow doctors to use smaller
amounts of radiation than the doses used in standard radiation therapy,
which could lead to fewer side effects.
Combining treatments
Another exciting area of research is looking at the use of PDT
along with current therapy to make it more effective. One way to do
this may be to use PDT during surgery to help keep cancer from coming
back on large surface areas inside the body, such as the pleura (lining
of the lung) and the peritoneum (lining of the abdomen). These are
common sites of spread for some types of cancer.
Interstitial treatments
Someday PDT may be used to help treat larger solid tumors,
too. A technique known as interstitial therapy involves using imaging
tests (such as CT scans) to guide fiber optics directly into tumors
using needles. This may be especially useful in areas that would
require major surgery. Early results of studies of interstitial therapy
in head and neck, liver, and pancreas tumors are promising.
Better understanding PDT
Researchers are also looking more closely at how PDT works and
how the cancer cells respond to its effects. Understanding how cells
respond to PDT may allow doctors to enhance those effects that promote
cancer cell death and suppress or counteract those that protect the
cancer cells. There may also be ways to pre-treat the tumor to make it
more susceptible to certain PDT treatments.
Summary
PDT has been used for the past 30 years and doctors know that
it works. PDT takes very little time, is often done as an outpatient,
can be accurately aimed at the affected area, can be repeated, and has
no long-term side effects. It also isn't as expensive or invasive as
some other cancer treatments. These are just a few of the advantages of
PDT. Researchers continue to look for ways to improve this cancer
treatment and find ways to combine it with other treatments to get even
better results.
Additional resources
More information from your American Cancer
Society
We have selected some related information that may also be
helpful to you. These materials may be viewed on our Web site at
www.cancer.org
or ordered from our toll-free number, 1-800-227-2345.
We also have more information about any of the types of cancer
mentioned here, such as how they are diagnosed, and their symptoms and
treatments.
No matter who you are, we can help. Contact us anytime, day or
night, for cancer-related information and support. Call us at
1-800-227-2345
or visit www.cancer.org.
References
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Hopper C. Photodynamic therapy: a clinical reality in the
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Manufacturer's Product Information. Metvixia Cream, 2004.
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National Cancer Institute. Photodynamic Therapy for Cancer:
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Accessed at www.cancer.gov/cancertopics/factsheet/Therapy/photodynamic
on May 8, 2009.
Ortel B, Shea CR, Calzavara-Pinton P. Molecular mechanisms of
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Roswell Park Cancer Institute. Photodynamic Therapy (PDT)
Center. 2009. Accessed at
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Last Medical Review: 05/26/2009
Last Revised: 05/26/2009
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