Background: The risk of cutaneous squamous cell carcinoma (cSCC) is significantly increased in organ transplant recipients (OTRs). Clearance of actinic keratoses (AKs) is generally regarded as a surrogate biomarker for cSCC prevention. OTR-cSCC chemoprevention with topical AK treatments has not been investigated in randomized controlled trials (RCTs), although there is evidence that 5% 5-fluorouracil (5-FU) may be chemoprotective in immunocompetent patients. Objectives: To assess the feasibility, activity and evaluation outcomes relevant to the design of a future phase III RCT of topical cSCC chemoprevention in OTRs. Methods: OTRs with 10 or more AKs in predefined areas were randomized 1 : 1 : 1 to topical 5-FU, 5% imiquimod (IMIQ) or sunscreen (sun-protective factor 30+) in a phase II, open-label RCT over 15 months. Feasibility outcomes included proportions of eligible OTRs randomized, completing treatment and willing to be re-treated. AK activity [AK clearance, new AK development, patient-centred outcomes (toxicity, health-related quality of life, HRQoL)] and evaluation methodology (clinical vs. photographic) were assessed. Results: Forty OTRs with 903 AKs were randomized. All feasibility outcomes were met (56% of eligible OTRs were randomized; 89% completed treatment; 81% were 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. Conclusions: 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.
Bibliographical noteFunding Information:
This was an investigator‐initiated and investigator‐led trial funded by the National Institute for Health Research via the Research for Patient Benefit programme (PB‐PG‐0110‐21244). The study was coordinated by and developed in collaboration with the Cancer Research UK Clinical Trials Unit (CRUKCTU), University of Birmingham. Staff at the CRUKCTU are supported by a core funding grant from Cancer Research UK (C22436/A25354). The study was also developed with support from the UK Dermatology Clinical Trials Network (UK DCTN), which is financially supported by the British Association of Dermatologists and the University of Nottingham. The National Cancer Research Institute Skin Cancer Clinical Studies Group were also involved in trial development. Commercial support was provided by MEDA pharmaceuticals who supplied the 5% 5‐fluorouracil and 5% imiquimod creams. No pharmaceutical company had any role in the design of the trial, collection or analysis of the data, or writing of the manuscript. The sponsor was Queen Mary University of London. The EudraCT number is 2013‐000893‐32.
© 2022 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.
- Clinical trial
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