PDT

From Kidney Cancer Resource

Contents 1 Overview 2 Key Points 3 Details 3.1 How PDT works 3.2 The nature of the PDT effect is attractive for several very important reasons: 3.3 Like all treatments, there are limitations. The most important ones are: 3.4 What is photodynamic therapy? 3.5 How is PDT used to treat cancer? 3.6 What types of cancer are currently treated with PDT? 3.6.1 When PDT is used 3.7 What are the limitations of PDT? 3.8 Does PDT have any complications or side effects? 3.8.1 Possible side effects of PDT also for head and neck cancers 3.8.1.1 Pain 3.8.1.2 Swelling 3.8.1.3 Constipation 3.8.1.4 Feeling sick (nausea) 3.8.1.5 Healing 3.9 What does the future hold for PDT? 4 Selected References 5 Disclaimer 6 E&OE - Errors & Omissions Excepted

Overview

PhotoDynamic Therapy or PDT

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Key Points

• Photodynamic therapy (PDT) combines a drug (called a photosensitizer or photosensitizing agent) with a specific type of light to kill cancer cells.
• The U.S. Food and Drug Administration (FDA) has approved the photosensitizing agent called porfimer sodium, or Photofrin®, for use in PDT to treat or relieve the symptoms of certain cancers.
• Patients treated with porfimer sodium should avoid direct sunlight and bright indoor light for at least 6 weeks after treatment.
• Researchers continue to study ways to improve the effectiveness of PDT and expand its use to other cancers.

Details

How PDT works

PDT is an exciting addition to the treatments available for a range of cancers. It is not going to cure all cancers and it is not going to displace all the conventional forms of therapy, but it does have the potential to add significant benefit to the results of Surgery and Radiotherapy. In some situations, it can stand alone.

The concept of PDT is simple. The patient is given a special drug that is sensitive to light. Then at a time from a few minutes to a few days later, red light (usually from a laser) is applied to the Tumour area. This activates the drug to kill the tissue in that area.

PDT works by killing cancers in two main ways. One way is to destroy the small blood vessels that supply the target tissue and so cut off the oxygen supply so that area of tissue dies. The other way is to destroy individual living cells. Inevitably, some normal cells will die as well as the cancer cells, but one of the beauties of PDT is that treated areas heal so well.

The nature of the PDT effect is attractive for several very important reasons:

1. It is gentle to tissue. There is no heat involved and treated areas heal remarkably well. This is true for almost all areas in the body, so once tumour areas have been treated with light, no more needs to be done. The normal body healing mechanisms clear up the dead tissue that has been left behind. For small tumours in sites like the skin and the mouth, the cosmetic result can be so good that it is difficult to see where the cancer was before treatment.

2. PDT can be applied to small areas of cancer that recur in sites previously treated with surgery or radiotherapy, although it cannot be used for large bulky areas of tumour recurrence.

3. Once a PDT treated area has healed, PDT can be used again in the same area, if the initial effect was not satisfactory. It is rarely possible to repeat surgery or radiotherapy at the same site.

4. In almost all cases, PDT is a “minimally invasive” treatment. The photosensitising drug is given by injection and the laser light is applied using one or more thin optical fibres (similar to a thick thread). For internal organs in the body like the gullet, stomach, lungs and bladder, the light is delivered using endoscopes (flexible telescopes that can be passed through natural body orifices such as the mouth, for access to the lungs and intestinal tract). Possible future applications such as for cancers of the pancreas and prostate would apply the light by passing the optical fibres through needles inserted through the skin into the target using image guidance from CT, MRI (magnetic resonance imaging) or ultrasound scans.

Like all treatments, there are limitations. The most important ones are:

1. PDT can only treat cancers that have stayed localised to the place where they started. It cannot treat cancers that have spread all over the body. Only chemotherapy (anti-cancer drugs) can do this.

2. PDT can only treat relatively small cancers, not large bulky ones.

3. PDT will affect normal tissues as well as cancerous ones. The effect is limited to the area of a cancer by controlling where the light is applied, but inevitably, some normal tissue will be affected where cancers meet normal tissue. Most normal tissues heal extremely well after PDT with little scarring, although especial care must be taken in some organs, such as the brain.

4. Some photosensitising drugs clear from the body within a few hours, but for those that take longer, patients need to take care to avoid bright lights, sometimes for several weeks, to minimise activation of drug still in the skin.

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What is photodynamic therapy?

Photodynamic therapy (PDT) is a treatment that uses a drug, called a photosensitizer or photosensitizing agent, and a particular type of light. When photosensitizers are exposed to a specific wavelength of light, they produce a form of oxygen that kills nearby cells.

Each photosensitizer is activated by light of a specific wavelength. This wavelength determines how far the light can travel into the body. Thus, doctors use specific photosensitizers and wavelengths of light to treat different areas of the body with PDT.

How is PDT used to treat cancer?

In the first step of PDT for cancer treatment, a photosensitizing agent is injected into the bloodstream. The agent is absorbed by cells all over the body, but stays in cancer cells longer than it does in normal cells. Approximately 24 to 72 hours after injection, when most of the agent has left normal cells but remains in cancer cells, the tumor is exposed to light. The photosensitizer in the tumor absorbs the light and produces an active form of oxygen that destroys nearby cancer cells.

In addition to directly killing cancer cells, PDT appears to shrink or destroy tumors in two other ways. The photosensitizer can damage blood vessels in the tumor, thereby preventing the cancer from receiving necessary nutrients. In addition, PDT may activate the immune system to attack the tumor cells.

The light used for PDT can come from a laser or other sources of light. Laser light can be directed through fiber optic cables (thin fibers that transmit light) to deliver light to areas inside the body. For example, a fiber optic cable can be inserted through an endoscope (a thin, lighted tube used to look at tissues inside the body) into the lungs or esophagus to treat cancer in these organs. Other light sources include light-emitting diodes (LEDs), which may be used for surface tumors, such as skin cancer.

PDT is usually performed as an outpatient procedure. PDT may also be repeated and may be used with other therapies, such as surgery, radiation, or chemotherapy.

What types of cancer are currently treated with PDT?

To date, the U.S. Food and Drug Administration (FDA) has approved the photosensitizing agent called porfimer sodium, or Photofrin®, for use in PDT to treat or relieve the symptoms of esophageal cancer and non-small cell lung cancer. Porfimer sodium is approved to relieve symptoms of esophageal cancer when the cancer obstructs the esophagus or when the cancer cannot be satisfactorily treated with laser therapy alone. Porfimer sodium is used to treat non-small cell lung cancer in patients for whom the usual treatments are not appropriate, and to relieve symptoms in patients with non-small cell lung cancer that obstructs the airways. In 2003, the FDA approved porfimer sodium for the treatment of precancerous lesions in patients with Barrett’s esophagus (a condition that can lead to esophageal cancer).

When PDT is used

PDT can be used to treat some cancers, or conditions that may develop into a cancer if not treated (precancerous). It is used when the affected area or the cancer is on or near the lining of internal organs. This is usually with cancers or conditions that affect:

• the skin (but not melanoma)
• the head and neck
• the mouththe lung
• the gullet (oesophagus)
• the stomach
• the bile ducts

Doctors are working to identify the types of cancer for which PDT is most effective. Research trials are taking place to look at new photosensitising agents, new laser and non-laser light treatments and ways of reducing the side effects.

Precancerous conditions PDT is used to treat precancerous conditions, such as Barrett's oesophagus and Bowen's disease of the skin.

Some research studies have used PDT to treat precancerous changes in the cells affecting the vulva (vulval intraepithelial neoplasia or VIN), the vagina and the anus.

Cancer In cancers that are being treated at an early stage, the aim of treatment may be to try to cure the cancer.

The aim of PDT for advanced cancer is usually to reduce symptoms by shrinking the tumour. In this situation PDT cannot cure a cancer.

PDT treatments for some cancers, such as prostate and pancreas, are still being researched.

Your doctor can advise you about whether PDT is an appropriate treatment in your situation, and whether you may be able to take part in any research trials.

PDT can safely be given to patients who have had other cancer treatments such as surgery, radiotherapy and chemotherapy.

What are the limitations of PDT?

The light needed to activate most photosensitizers cannot pass through more than about one-third of an inch of tissue (1 centimeter). For this reason, PDT is usually used to treat tumors on or just under the skin or on the lining of internal organs or cavities. PDT is also less effective in treating large tumors, because the light cannot pass far into these tumors. PDT is a local treatment and generally cannot be used to treat cancer that has spread (metastasized).

Does PDT have any complications or side effects?

Porfimer sodium makes the skin and eyes sensitive to light for approximately 6 weeks after treatment. Thus, patients are advised to avoid direct sunlight and bright indoor light for at least 6 weeks.

Photosensitizers tend to build up in tumors and the activating light is focused on the tumor. As a result, damage to healthy tissue is minimal. However, PDT can cause burns, swelling, pain, and scarring in nearby healthy tissue. Other side effects of PDT are related to the area that is treated. They can include coughing, trouble swallowing, stomach pain, painful breathing, or shortness of breath; these side effects are usually temporary.

Possible side effects of PDT also for head and neck cancers

Sensitivity to light Although the photosensitising drugs are mostly taken up by the cancer cells and are concentrated there, they can also make your ordinary skin cells, or your eyes, highly sensitive to light. People who have had PDT are advised to protect themselves from exposure to sunlight and bright indoor lighting. The duration of sensitivity to light (photosensitivity) varies depending upon which drug is used. The drug temoporfin (Foscan®) is commonly used to treat head and neck cancers and will make you sensitive to direct sunlight for up to a month.

While your skin is photosensitive, it is advisable to avoid going outside during the day. However, you do not need to stay in total darkness during this time. To start with you will need to stay in a darkened room, but you can gradually build-up the amount of light over two weeks. If you need to go out, use clothing to cover your skin: for example, wear a brimmed hat, scarf, long-sleeved shirt or blouse and trousers, gloves and dark glasses. Using sunscreens will not give you any additional protection.

You can go out uncovered very early in the morning or after sunset, and you can use low-level artificial light indoors (maximum 60W bulb). In the first few days it is possible to get ‘sunburn’ even on a dull winter day. You will not notice that you are getting burnt while you are out in the sun. As with sunburn, the damage to your skin can take a few hours to show up.

You can even get burnt through glass if the light is strong. Remember to draw curtains during the day if the sun is bright. Bright artificial lights can also cause a skin reaction, so spot lamps are best avoided. It is important to be aware of unexpected sources of light – for instance, warming your hands over a fire could result in being burnt. It is also a good idea not to use a computer during this time and not to watch the television from less than about 2 metres (6 feet) away. You may be given a light meter to use at home, to check that the light intensity is at a safe level.

It is advisable to avoid opticians’ appointments around the time of your treatment, as the retinas inside your eyes will be more vulnerable to light than usual, and you should not have light shone into your eyes.

Towards the end of the time of photosensitivity, a small area of skin can be exposed to brighter light for five minutes and the reaction assessed 24 hours later. Your doctors will advise you on how to do this. After this time, you will be able to gradually increase the amount of light you are exposed to and most people are able to go outside as usual after approximately three weeks. Your doctor or specialist nurse can let you know for exactly how long you will need to protect your skin.

Pain

Treatment with PDT can cause pain in the tumour area. Your specialist nurse should be able to tell you how much pain you might expect and see that you are given appropriate painkillers. The amount of pain will vary according to where your tumour is and which light-sensitising drug has been used. Pain can range from mild to severe. For some treatments aspirin or paracetamol may be enough, however for others a morphine-type drug may be necessary. If you have pain, it is important to let your doctor know, so that you can be given effective and appropriate painkillers.

Swelling

Some photosensitising drugs can cause swelling in the treated area. This varies from one person to another. If you have had treatment in your mouth or throat, the swelling may make it difficult to swallow. It is important to let your nurse or doctor know if swallowing becomes very difficult. The swelling is only temporary but can be treated with steroid injections or drugs that help to reduce inflammation.

Constipation

This is a fairly common side effect of PDT and you may need to ask your doctor for medication.

Feeling sick (nausea)

Some people may feel sick, which can be controlled with mild anti-sickness tablets if necessary.

Healing

PDT causes much less scarring than surgery. However, the time taken for PDT-treated areas to heal can vary a lot. It may be several weeks, depending on the area treated and how deeply the light has penetrated into the body tissues.

What does the future hold for PDT?

Researchers continue to study ways to improve the effectiveness of PDT and expand it to other cancers. Clinical trials (research studies) are under way to evaluate the use of PDT for cancers of the brain, skin, prostate, cervix, and peritoneal cavity (the space in the abdomen that contains the intestines, stomach, and liver). Other research is focused on the development of photosensitizers that are more powerful, more specifically target cancer cells, and are activated by light that can penetrate tissue and treat deep or large tumors (2). Researchers are also investigating ways to improve equipment and the delivery of the activating light.

Selected References

• Dolmans DEJGJ, Fukumura D, Jain RK. Photodynamic therapy for cancer. Nature Reviews Cancer 2003;3(5):380–387.

• Wilson BC. Photodynamic therapy for cancer: Principles. Canadian Journal of Gastroenterology 2002;16(6):393–396.

• Vrouenraets MB, Visser GWM, Snow GB, van Dongen GAMS. Basic principles, applications in oncology and improved selectivity of photodynamic therapy. Anticancer Research 2003;23:505–522.

• Dougherty TJ, Gomer CJ, Henderson BW, et al. Photodynamic therapy. Journal of the National Cancer Institute 1998;90(12):889–905.

• Dickson EFG, Goyan RL, Pottier RH. New directions in photodynamic therapy. Cellular and Molecular Biology 2003;48(8):939–954.

• Capella MAM, Capella LS. A light in multidrug resistance: Photodynamic treatment of multidrug-resistant tumors. Journal of Biomedical Science 2003;10:361–366.

• U.S. Food and Drug Administration (December 2003). Approved claims for palliative line therapy. Retrieved December 29, 2003, from: Click Here.

• U.S. Food and Drug Administration (August 2003). FDA approves photofrin for treatment of pre-cancerous lesions in Barrett’s esophagus. Retrieved December 29, 2003, from: Click Here.

• U.S. National Institute of Health (Cancer) Click Here.

• Oxford Textbook of Oncology (2nd edition). Souhami et al. Oxford University Press, 2002.

• Cancer and its Management (4th edition). Souhami and Tobias. Oxford Blackwell Scientific Publications, 2003.

• The Textbook of Uncommon Cancers (3rd edition). Raghavan et al. Wiley, 2006.British National Formulary (54th edition).

• British Medical Association and Royal Pharmaceutical Society of Great Britain. September 2007.

• CancerBackUp Click Here.

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E&OE - Errors & Omissions Excepted