Topical treatment of actinic keratoses in organ transplant recipients: a feasibility study for SPOT (Squamous cell carcinoma Prevention in Organ transplant recipients using Topical treatments)

Zeeshaan-Ul Hasan, Ikhlaaq Ahmed, Rubeta N Matin, Victoria Homer, John T Lear, Ferina Ismail, Tristan Whitmarsh, Adele C Green, Jason Thomson, Alan Milligan, Sarah Hogan, Vanessa Van-de-Velde, Liza Mitchell-Worsford, Jonathan Kentley, Sarah Bowden, Piers Gaunt, Keith Wheatley, Charlotte M Proby, Catherine A Harwood

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
JournalBritish Journal of Dermatology
Early online date5 Jan 2022
DOIs
Publication statusE-pub ahead of print - 5 Jan 2022

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