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)

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.

A Review of Cutaneous Squamous Cell Carcinoma Epidemiology, Diagnosis, and Management

“…Studies have shown mixed results in the risk reduction associated with acitretin. An RCT of 70 healthy patients with a history of NMSC found a 59% decrease odds of new NMSC in a 2-year period (acitretin: 54%, control: 74%; P = 0.13), although this did not meet statistical significance (83). A systemic review of 3 RCTs of acitretin in solid organ transplant recipients (SOTR) noted less CSCC development in patients receiving acitretin (84).…”

Diagnosis and treatment of invasive squamous cell carcinoma of the skin: European consensus-based interdisciplinary guideline

“…In this regard, radiotherapy represents the best alternative to surgery, but cannot be advised as a rule given its side-effects and limitations. Although neoadjuvant use of oral retinoids (acitretin) may decrease the size of the tumour and reduce the overall tumour load in cases with multiple SCCs, there is currently a lack of supporting evidence from randomised studies [57].…”

Guidelines of care for the management of basal cell carcinoma

“…125 Oral retinoids (acitretin, oral retinol, and isotretinoin) also do not appear to reduce the incidence of BCC in those with a history of a keratinocyte cancer. [126][127][128][129] Limited evidence is available to support the utility of other agents, including oral nicotinamide, a-difluoromethylornithine, and celecoxib, in reducing the risk for keratinocyte cancer in patients with history of BCC. There is early evidence from a small trial that oral nicotinamide may reduce the risk for subsequent keratinocyte carcinoma in nonimmunosuppressed individuals with a history of such Table XIII.…”

“…[116][117][118][119]123,[125][126][127][128][129][130][131][132][133][134][135][136][137][138][139][140][141] …”