Reducing the risk: Fighting the incidence of non-melanoma skin cancers with retinoids

October 1, 2008

The development of non-melanoma skin cancer is a common sequela of the high doses of immunosuppressive medications that organ transplant recipients receive. A recent study shows that low-dose systemic retinoids can significantly decrease these patients' susceptibility to develop skin cancers (such as squamous cell carcinoma) in the long term.

Key Points

International report - Organ transplant recipients (OTRs) are at an especially high risk of developing non-melanoma skin cancers due to the necessary therapeutic administration of oral immunosuppressive medications such as cyclosporine and corticosteroids.

According to the results of a recent study, low-dose systemic retinoids can reduce the significant increase in incidence of squamous cell skin cancers in these patients.

It is difficult for healthcare professionals to properly balance the level of immunosuppression that transplant recipients need to receive against the attendant risk of these medications.

The cumulative risk of non-melanoma skin cancer in OTRs is more than 40 percent by 20 years after transplantation in temperate climates, and rises to more than 80 percent in Australia.

Retinoid study

Charlotte Proby, F.R.C.P., consultant dermatologist at the Centre for Cutaneous Research, Barts, and The London Queen Mary's School of Medicine and Dentistry, University of London, conducted a 16-year retrospective study in 32 OTRs with skin cancer, and evaluated the long-term efficacy of systemic retinoids in reducing the incidence of cutaneous SCCs.

In the study, patients received a continuous administration of systemic acitretin, dosed at 0.2 to 0.4 mg per kg per day for a minimum of 12 months and a maximum of 16 years.

The main study endpoint was the mean difference between the number of SCCs developing during annual retinoid treatment and the number developing during the 12-month pre-treatment interval.

Results

Results showed that systemic retinoids at low doses can significantly reduce the development of SCC for the first three years of treatment, and this tumor suppression effect can be sustained for at least eight years.

The patients in the study showed a good tolerance for the low-dose retinoid therapy, reflected in the limited adverse event profile.

"Our study examined the number of skin cancers in all our patients who had been on long-term low-dose acitretin," Dr. Proby tells Dermatology Times. "With low-dose acitretin, we were looking to affect a reduction in the skin cancer numbers rather than no skin cancers at all.

"This approach is important, because it is essential that these high-risk skin cancer patients continue with the treatment long term, and high doses of oral retinoids tend to give too many side-effects," she adds. "If they stop treatment, there is a rebound effect when they get many more skin cancers."

In the 28 patients who kept to the strict study protocol with no treatment breaks, the mean number of SCCs in the 12-month pre-treatment interval was 2.9.

The number of SCCs in these patients was significantly reduced with the continuous acitretin therapy, showing a mean difference of 1.46, 2.20 and 2.14 SCCs in the first, second and third year of treatment, respectively.

Dr. Proby says that the number of SCCs was reduced in subsequent years; however, this effect was no longer significant due to the smaller number of patients.

How retinoids work

Retinoid therapy likely works by 'holding' the skin cancer in check by increasing the differentiation of the epidermis. If this 'check' is taken away, the skin cancers that would have appeared in the preceding months or years are able to progress.

According to Dr. Proby, this is the first study that looked at patients taking systemic retinoids for such a long period. One of the strict exclusion factors in the study included those participants who had even the shortest break in treatment protocol.

"This explains why the final number of patients who completed the study was rather small," Dr. Proby says. "We could only show a statistically significant effect on skin cancer numbers for the first three years on treatment.

"The benefits seemed to continue for at least eight years, but we would need larger numbers of patients on this very long-term treatment to show this," Dr. Proby adds.

Chemoprevention

According to Dr. Proby, there are continuing attempts to find a new "chemoprevention" agent that can be taken orally.

"There has been a lot of interest in the therapeutic effect of antioxidant agents to reduce non-melanoma skin cancers, particularly naturally occurring agents, such as green Tea polyphenols.

"However, to date, although they seem to reduce and/or prevent skin cancers in mouse models of skin carcinogenesis, they haven't been shown to make any difference in trials in humans," Dr. Proby says.

At the present time, topical chemoprevention treatments - such as Aldara, Efudix and Solaraze creams directed at treating areas of abnormal sun-damaged skin - may be a more effective approach for reducing skin cancers, Dr. Proby explains.

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