Reducing risks: Systemic retinoids useful for nonmelanoma skin cancer

Key Points

Role of systemic retinoids

Retinoids represent a group of vitamin A derivatives and synthetic analogs that are known to modulate fundamental physiologic processes, including embryonal development, cellular proliferation, differentiation and apoptosis.

The use of systemic retinoids in skin cancer has been looked at from several perspectives - nonmelanoma and melanoma skin cancer, as well as cutaneous lymphomas.

"While experimental and clinical data suggest a beneficial modulatory effect of retinoids in melanoma, the associated toxicity observed with long-term systemic use and the need for a large population sample to evaluate its efficacy has hampered the interest in considering further long-term, randomized clinical studies," Dr. Curiel tells Dermatology Times.

The application of systemic retinoids is more successful with nonmelanoma skin cancer; in particular, squamous cell carcinoma (SCC).

"Patients developing a significant number of SCCs, in particular six or more per year, have found a significant benefit form this type of intervention.

"Chronically immunosuppressed patients, such as solid organ transplant (patients) and those with history of significant UV exposure, such as phototherapy patients with greater than 250 treatments, represent a group of patients with demonstrated benefit from this intervention," Dr. Curiel says.

Transplant patients

"Immunosuppressed transplant patients are known to have a significant risk to develop skin cancer, in particular SCCs. The risk seems to be proportionally related to the type, intensity and length of the immunosuppressive regimen and degree of prior UV exposure," Dr. Curiel says.

"The ratio of SCC to BCC is altered to such an extent, that the incidence of SCCs outnumber BCCs by a ratio of between 2:1 to 3.5:1 in transplant recipients, compared with a ratio of between approximately 1:4 to 1:10 in immunocompetent individuals, where BCC is the most common skin cancer (Eye. 2002).

"In addition to the higher incidence rate, a higher risk of metastasis is observed in this these patients were SCCs present with a more aggressive behavior. In some instances, SCC is the cause of death for some of these patients," Dr. Curiel says.

Systemic retinoids are often used as a chemopreventive agent to decrease the number of developing tumors in individuals who have had significant sun damage and who are post-transplant and have started to develop multiple SCCs (more than six to eight in a year). Acitretin (Soriatane, Stiefel) is the most commonly used systemic retinoid in these cases.

"Acitretin was initially indicated for the treatment of psoriasis patients; it has also found a niche in the chemoprevention of nonmelanoma skin cancer. Several case series and case-controlled studies have demonstrated its effectiveness," Dr. Curiel says.

There are systemic side effects associated with Acitretin, including xerosis, hypertriglyceridemia and abnormal liver function test, and there are other symptoms such as hair loss, arthralgia, myalgia and headaches. The drug cannot be used during pregnancy or in women who intend to become pregnant, because of several fetal abnormalities documented with use of systemic retinoids.