BACKGROUND: Cutaneous squamous cell carcinoma (CSCC) risk is significantly increased in organ transplant recipients (OTRs). Clearance of actinic keratoses (AK) is generally regarded as a surrogate biomarker for CSCC prevention. OTR-CSCC chemoprevention with topical AK treatments has not been investigated in randomised controlled trials (RCT), although there is evidence that 5% 5-fluorouracil (5-FU) maybe chemoprotective in immunocompetent patients.
OBJECTIVES: To assess feasibility, activity and evaluation outcomes relevant to design of a future phase III RCT of topical CSCC chemoprevention in OTRs.
METHODS: OTRs with 10 or more AKs in predefined areas were randomised 1:1:1 to topical 5-FU, 5%-imiquimod (IMIQ) or sunscreen (SPF 30+) in a phase II, open-label RCT over 15 months. Feasibility outcomes included proportions of eligible OTRs randomised, completing treatment and willing to be retreated. AK activity (AK clearance, new AK development, patient-centred outcomes (toxicity, health-related quality of life [HRQoL]) and evaluation methodology (clinical versus photographic) were assessed.
RESULTS: Forty OTRs with 903 AKs were recruited. All feasibility outcomes were met (67% of eligible OTRs randomised; 88 % completed treatment; 95% willing to be re-treated). AK activity analyses found 5-FU and IMIQ were superior to sunscreen for AK clearance and prevention of new AKs. 5-FU was more effective than IMIQ in AK clearance and prevention in exploratory analyses. Although toxicity was greater with 5-FU, HRQoL outcomes were similar.
CONCLUSION: Trials of topical AK treatments in OTRs for CSCC chemoprevention are feasible and AK activity results support further investigation of 5-FU-based treatments in future phase III trials.