Randomized controlled trial of acitretin versus placebo in patients at high-risk for basal cell or squamous cell carcinoma of the skin (North Central Cancer Treatment Group Study 969251)

Cancer. 2012 Apr 15;118(8):2128-37. doi: 10.1002/cncr.26374. Epub 2011 Aug 31.

Abstract

Background: Chemoprevention with systemic retinoids has demonstrated promise in decreasing the incidence of new primary nonmelanoma skin cancers (NMSCs) in immunocompromised post-transplantation recipients. There is limited evidence for the use of systemic retinoids in the nontransplantation patient. To the authors' knowledge, this is the first randomized controlled trial to assess the efficacy of acitretin as a chemopreventive agent in nontransplantation patients at high-risk for NMSC.

Methods: The study was designed as a prospective, randomized, double-blind, placebo-controlled clinical trial. To test the possible skin cancer-preventing effect of a 2-year treatment with acitretin, 70 nontransplantation patients aged ≥18 years who had a history of ≥2 NMSCs within 5 years of trial onset were randomized to receive either placebo or acitretin 25 mg orally 5 days per week. The primary outcome measure was the rate of new NMSC development.

Results: Seventy patients were randomized to receive either acitretin alone (N = 35) or placebo (N = 35). During the 2-year treatment period, the patients who received acitretin did not have a statistically significant reduction in the rate of new primary NMSCs (odds ratio, 0.41; 95% confidence interval, 0.15-1.13; 54% vs 74%; P = .13). However, using the incidence of new NMSC, the time to new NMSC, and total NMSC counts, an umbrella test indicated a significant trend that favored the use of acitretin (chi-square statistic, 3.94; P = .047). The patients who received acitretin reported significantly more mucositis and skin toxicities compared with the patients who received placebo.

Conclusions: Although there was not a statistically significant benefit observed with the use of acitretin, this may have been the result of low statistical power.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Acitretin / adverse effects
  • Acitretin / therapeutic use*
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Carcinoma, Basal Cell / prevention & control*
  • Carcinoma, Squamous Cell / prevention & control*
  • Double-Blind Method
  • Female
  • Humans
  • Male
  • Middle Aged
  • Neoplasms, Second Primary / prevention & control
  • Placebos
  • Retinoids / therapeutic use
  • Risk
  • Skin Neoplasms / drug therapy*
  • Skin Neoplasms / pathology
  • Skin Neoplasms / prevention & control*
  • Time Factors

Substances

  • Antineoplastic Agents
  • Placebos
  • Retinoids
  • Acitretin