Chemo Prevention of Skin Cancer in Transplant Recipients Using Systemic Retinoids

Organ Transplant & Skin Cancer

Non-melanoma skin cancers (NMSC) are amongst the most common human cancers in the world. Cumulative sun exposure has been found to be the biggest risk factor for skin cancers.

Several genetic and environmental factors are known to cause the disease.

Risk factors for NMSC include the following -

·        UV Radiation

·        Immuno suppression

·        Chronic inflammation

·        Radiation

·        Infection with human papilloma virus (oncogenic strains)

Surgical excision is the best-known therapy for most NMSCs. Non-invasive treatment options include the drug imiquimod and photodynamic therapy.

Solid organ transplant recipients (OTRs) are at an increased risk (64-250 times in comparison to general population) of skin cancer. This could result in significant morbidity and mortality. Therefore, chemo preventive therapies have been used to reduce and delay the development of skin cancer in these individuals.

A review of literature was carried out to evaluate the effect of retinoids in preventing skin cancer in transplant patients.

Retinoids

Chemoprevention strategies in transplant patients are usually focused on reducing and delaying the development of skin cancer.

Systemic retinoids have been widely used in preventing skin cancer in OTRs; however, very few randomized controlled trials have been carried out to establish this fact.

Retinoids, are natural and synthetic derivatives of vitamin A. They are protective against several types of cancers. The anti- cancer mechanism of retinoids remains largely unknown.

Some of the known mechanisms include - induction of apoptosis, effects on cell cycle control, immuno modulation, inhibition of ornithine decarboxylase, inhibition of cellular proliferation and keratinization, and promotion of cellular differentiation.

 Experimental data indicate that retinoids are most effective during the promotion and progression stages of cancer.

Method 

In a prospective, open, randomized, crossover trial, George et al. tried to evaluate the efficacy of acitretin, a second-generation retinoid, in controlling NMSC development in renal transplant recipients.

25 mg of acitretin was administered to 14 patients per day. Nine patients received no therapy. Only 47.8% of patients completed the two-year trial.

Bouwes Bavinck et al. did a randomized, double blind, placebo-controlled trial to study the effect of 30 mg of acitretin per day on NMSC development in renal transplant recipients.

In a retrospective before-after study, Harwood et al. analyzed the efficacy of acitretin in preventing skin cancers in organ transplant recipients.

Conclusion

An analysis of these studies suggests that acitretin may have a beneficial role in high-risk OTRs. The major drawback with retinoids is poor tolerability.Cheilitis, xerosis, skin peeling, photosensitivity alopecia, headaches, and dyslipidemia are some of the side-effects reported. This often results in dose reductions. A starting dose of 10 mg per day has been recommended which may be increased to 30 mg per day.

Chemoprevention with retinoids must be lifelong to prevent recurrence. Further studies are required to establish the efficacy and long-term safety of systemic retinoids and to further understand their role as chemo preventive agents for high-risk transplant recipients.

Source: Systemic Retinoids: Chemoprevention of Skin Cancer in Transplant Recipients; Skin Therapy 2011. 

Source: Medindia