Acitretin for chemoprevention of non‐melanoma skin cancers in renal transplant recipients

Abstract

A prospective, open randomized crossover trial was conducted to evaluate the efficacy of acitretin for chemoprevention of squamous cell carcinomas and basal cell carcinomas in renal allograft recipients. Analysis was performed according to the intention-to treat principle. Twenty-three patients with previous history of non-melanoma skin cancer enrolled into the study and were randomly allocated into two groups. They crossed over at the end of 1 year. Eleven (47.8%) patients completed the 2-year trial. Twelve (52.2%) patients withdrew from the trial. Nine of these withdrew because of side-effects of acitretin. The majority of the patients who continued with the acitretin could tolerate 25 mg of acitretin daily or on alternate days. The number of squamous cell carcinomas (SCC) observed in patients while on acitretin was significantly lower than that in the drug-free period (P = 0.002). A similar trend was observed in patients with basal cell carcinomas, but this was not significant and the numbers were small. Side-effects were a major limiting factor. A severe rebound increase in SCC occurred in one patient after the acitretin was ceased.

Low-Dose Retinoids in the Prevention of Cutaneous Squamous Cell Carcinomas in Organ Transplant Recipients

“…18 Eleven patients completed a randomized crossover trial in which acitretin produced a significant reduction in SCCs compared with no treatment during 12 months. 19 In a third trial of 26 patients randomized to treatment with 2 dosages of acitretin (0.2 vs 0.4 mg/kg per day) during 12 months, a significant reduction was seen in actinic keratoses but not SCCs in both groups. 20 Retinoids are effective only during treatment, such that lifelong administration is potentially required for prevention of SCCs in OTRs.…”

“…A similarly high level of mucocutaneous side effects has been reported in other studies. 15,[18][19][20] More than half of all patients had increased lipid levels before starting retinoids, and most were already receiving treatment for this, reflecting the rigorous optimization of lipid levels required in these individuals, given their increased risk of cardiovascular disease. Only 2 individuals with normal lipid levels before retinoid therapy had an increase in lipid levels while taking retinoids that required the introduction of lipid-lowering drugs.…”

British Association of Dermatologists guidelines on the efficacy and use of acitretin in dermatology

“…Longer-term studies had differing dose regimens. In the study by George et al 51 acitretin was titrated from 25 mg daily up to 50 mg daily or down to 25 mg on alternate days. In the crossover study there was a 42% decrease in squamous cell carcinoma in the acitretin period compared with drug-free period.…”

Off-label uses of retinoids in dermatology

“…Combined therapy with isotretinoin and INF-2α was highly effective in advanced squamous cell carcinoma. Acitretin treatment (30-50 mg/day over 6 months) appears to decrease the number of new squamous cell carcinomas and ameliorates the aspect and reduces the number of actinic keratoses [101][102][103].…”

“…Well tolerated lowdose acitretin (0·3 mg/kg daily) has proven to be a useful chemopreventative strategy in the management of renal transplant recipients with widespread epidermal dysplasia and multiple NMSC (both SCC and BCC). Acceptance of a partial prophylactic effect using a well tolerated low dose of acitretin may be preferable compared with a higher dosage and the likelihood of inducing toxic side-effects that patients would not tolerate long-term [102,116].…”