Metvix cream (methylaminolevulinate)
Metvix cream contains methylaminolevulinate, a new medicinal product for the non-invasive treatment of certain types of actinic keratoses and superficial and/or nodular basal cell carcinoma in patients for whom other therapies are considered less suitable. There are no other medicinal products of this type on the Danish market at this time. Metvix cream may only be used at hospitals and by dermatologists.
The efficacy of the product has been demonstrated in several studies, and it is apparently fairly well tolerated. Unfortunately, it is an extremely expensive cream: two grams costs DKK 1,552.65. However, the high cost should be held up against that of the other therapies available.
Metvix cream was marketed on 24 June 2002. It contains the active ingredient methylaminolevulinate, a new cytostatic compound without analogue on the Danish medicinal products market. Two alternative therapies are cryotherapy or surgery. Metvix cream is approved for two indications:
Treatment of thin or non-hyperkeratotic and non-pigmented actinic keratoses on the face and scalp in those patients for whom other therapies are considered less suitable.
Only for treatment of superficial and/or nodular basal cell carcinoma considered unsuitable for treatment with other available therapies, e.g. lesions on the mid-face or ears, lesions on severely sun-damaged skin, or large or recurrent lesions.
Application of methylaminolevulinate results in an intracellular accumulation of porphyrines in the treated skin lesions. These porphyrines are photoactive, and their subsequent exposure to light causes the formation of oxygen radicals that cause cell damage, especially through their effect on cell mitochondria.
The cream is applied twice, the second time a week after the first. After application, the cream is to remain on the skin for three hours under occlusion. The lesion is then exposed to red light with a continuous spectrum of 570-670 nm. Metvix cream may be dispensed to hospitals and dermatologists only.
Three studies have been conducted to demonstrate the product’s efficacy in the treatment of actinic keratosis. In two of the studies, Metvix was compared to placebo; the study populations numbered 39 and 111 patients. The primary efficacy parameter in both studies was a physician assessment of "excellent response", and Metvix showed significant efficacy in both studies. In the third study, which featured a population of 202 patients, Metvix therapy was compared with cryotherapy: no significant difference between the two therapies was seen.
Two studies, both open, were conducted to show the efficacy of Metvix in the treatment of basal cell carcinoma. In the first study, 146 patients were randomised to a 3-, 5- or 18-hour application of Metvix prior to light treatment. Patient response was 89-93%, largely independent of application time. The population of the other study were 94 patients for whom traditional therapy was considered unsuitable. An "excellent response" rate of 82% and a recurrence rate of 6% were observed.
There is no experience of treating patients below the age of 18.
Adverse drug reactions
The most pronounced adverse effect of the treatment is phototoxicity, which occurred in between 60% and 80% of the patients in the clinical trials, particularly in the form of a burning sensation, crusting, local pain and oedema. These adverse effects are mild to moderate and usually transitory, but oedema and erythema may persist for one to two weeks. So far there have only been isolated reports of other adverse effects, e.g. anxiety, headache, dizziness, nausea and fatigue, and it is uncertain whether they are related to methylaminolevulinate therapy.
As a result of the poor systemic absorption of methylaminovulinate, no reproductive toxicity studies have been conducted. No specific interaction studies have been performed, either, since dermal application results in virtually no systemic absorption of the active ingredient.
Two grams of Metvix creme costs DKK 1,552.65, but this must be seen in the light of the cost of the other therapies available.
Last modified: June 24th 2002