PDT

What is photodynamic therapy ?

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.



source: cancer.org