Methyl aminolevulinate photodynamic therapy (MAL PDT)

Methyl aminolevulinate

Methyl aminolevulinate (MAL) is a topical photosensitising agent that is used in photodynamic therapy (PDT). It is available as a 16% strength cream in a 2g tube. The trade name is Metvix™.

Metvix movie

How does methyl aminolevulinate PDT work?

When applied to the skin, methyl aminolevulinate is selectively absorbed into cancer cells. The drug is converted into photoactive porphyrins, naturally-occurring intracellular photosensitising chemicals that bind with iron to make haemoglobin. When cancer cells full of porphyrins are exposed to specific wavelength of light (570-670 nm), a molecular reaction occurs that results in destruction of the cancer cells.

What is methyl aminolevulinate PDT used for?

Methyl aminolevulinate is classed as an antineoplastic agent (anti-cancer drug) and is approved for use in New Zealand for the treatment of:

• Thin solar keratoses (sun spots) on the face and scalp
• Superficial and/or thin nodular basal cell carcinomas

MAL-PDT is recommended for lesions that are unsuitable for other available therapies due to possible complications and/or poor cosmetic outcome. It may be particularly useful for lesions on the mid-face or ears, lesions on severely sun damaged skin, large lesions or recurrent lesions.

Clinical trials around the world using MAL-PDT have shown it to have comparable cure rates to other conventional treatments such as cryotherapy or surgery. A distinct advantage of MAL-PDT is that it selectively targets tumour cells. This means that surrounding healthy cells are not affected by the treatment thus leaving minimal scarring and a much better cosmetic outcome.

How is MAL-PDT given?

MAl-PDT involves a two-stage process. The first stage is application of the methyl aminolevulinate cream.

PDT for solar keratoses

Solar keratoses

Applying Metvix® cream

Protecting treated area

• Prepare the surface of the skin lesion by removing scales and crusts (light scraping, curretage or superficial microneedling). The top of the lesion may need to be removed so that it is less than 1 mm in thickness.
• Using a spatula apply a 1mm thick layer of methyl aminolevulinate cream to the lesion and surrounding 5 mm of normal skin.
• Cover with an occlusive dressing for 3 hours. During this time you may be allowed to leave the surgery as long as you do not disturb the dressing and keep it out of direct sunlight.

Metvix PDT

Small Aktilite lamp

Large Aktilite lamp

Patient undergoing treatment

The second stage involves exposing the lesion to light.

• Remove dressing and clean treatment area with saline to remove methyl aminolevulinate cream.
• Lignocaine (lidocaine) spray or cooling fan may be applied to relieve burning sensation and pain that may occur. Pain killers may be necessary.
• Expose lesion to red light with a continuous spectrum of 570-670 nm and a total dose of 75 J/cm². A source of red light with a narrower spectrum may be used, e.g. Aktilite (illustrated, wavelength 630nm, 70-100mW/cm²). Both doctor and patient should wear protective eye goggles and the light source should be 50mm from the skin lesion. Treatment may take 5-15 minutes.
• Light intensity at the lesion surface should not exceed 200 mW/cm2.

After treatment the lesions will be covered with an occlusive dressing for at least 24 hours. Lesions usually heal completely within one to four weeks. More than one lesion can be treated in a single treatment session. A repeat second treatment may be done approximately one week later: this is recommended for most basal cell carcinomas and thicker solar keratoses.

Your practitioner will arrange to check the lesions after about 3 months. If they show a non-complete response re-treatment may be necessary.

Basal cell carcinoma treated with PDT

Prior to treatment	Lesion scraped just before Metvix® cream application
One week after MAL PDT	One month after MAL PDT No sign of original lesion

Precautions

• The safety of MAL PDT has not yet been established in patients under 18 years old, but skin cancers very rarely affect this age group.
• The safety of MAL PDT has not yet been established in pregnancy or breastfeeding. It is therefore not recommended for use during pregnancy.
• Discontinue breastfeeding for 48 hours after application of methyl aminolevulinate.
• Hypersensitivity or allergic reactions to active substance or any of the excipients may occur. These include:
  • Arachis (peanut) oil
  • Cetostearyl alcohol
  • Methyl- and propyl-para hydroxybenzoate (E218, E216)
• Avoid sun exposure on treated lesions sites for at least a couple of days following treatment.

If the treatment is very painful, exposure to the light can be temporarily stopped. When ready to recommence, the light source can be moved further away (e.g. twice the distance) from the treatment area, and exposure recommenced. The exposure time will need to be adjusted (e.g. twice as long for the remaining exposure). Slower treatments are usually less painful.

Side effects of MAL-PDT

Approximate 60-80% of patients undergoing MAL-PDT experience some side effects. These are usually related to the treated area being sensitive to light and are like sunburn. Side effects are of mild to moderate intensity and usually subside within a few days after treatment.

As the skin cancers cells die off, the lesion may blister and ulcerate. This generally heals within 4 weeks.

Storage and handling

• Store Metvix® cream in a refrigerator (below 8C)
• Discard 1 week after opening the tube

Metvix movie

The Metvix™ QuickTime movie is approx 2 1/2 minutes in duration (4.3MB). Click here to view the movie.
 
If you don't have QuickTime please click on the Download QuickTime button below.
 

PDT using natural daylight

Daylight-mediated PDT has been described for the treatment of thin solar keratoses. Results have been shown to be as good as with conventional MAL-PDT (described above). Treatment can be undertaken during spring, summer or autumn in most parts of the world.

The natural daylight PDT procedure is as follows:

• A suitable day is selected for treatment; overcast with temperature over 10C is best.
• The field to be treated is marked out
• The keratoses are lightly scraped
• A clear sunscreen is applied to all skin to be exposed to sunlight including intended treatment area
• 15 minutes later, methyl aminolevulinate cream is applied to the field
• Half an hour later, the patient should go outdoors to expose the treated area to daylight. If it is sunny during summer, stay in the shade.
• Two hours later, return to the office to have the cream washed off using saline.
• Remain indoors for the rest of the day.

As described above, natural daylight PDT is followed by sunburn-like inflammation in treated areas for 5 to 8 days. The skin is red, and may become blistered and crusted.

Similar cure rates and excellent cosmetic results are described. Advantages of natural daylight PDT include:

• The procedure is less painful
• Large areas of sun damage can be treated on a single occasion
• The procedure may prove less expensive