Cutaneous SCC prevention using topical therapy in immunosuppressed patients (SPOT-IT)

Research summary

Background: Cutaneous squamous cell carcinoma (cSCC) is the most common skin cancer with metastatic potential and has an identifiable precancerous stage,actinic keratosis (AK). cSCC incidence exceeds 52,000 in UK and is increasing by 5% per annum with immunosuppression as a key risk factor. Multiple primary cSCC are common,especially in immunosuppressed organ transplant recipients,and incur significant morbidity and cost. Prevention of cSCC in immunosuppressed patients is a major unmet clinical need,yet this population has previously been excluded RCT data confirm that 5-fluorouracil 5% cream (5FU,Efudix) is the most effective treatment modality for AK in immunocompetent patients but is difficult to tolerate and is likely to be repeated annually (twice daily for 4 weeks with a significant local skin reaction). Recent evidence finds combining 5FU with topical calcipotriol ointment (5FU+CAL) potentiates efficacy,reducing treatment time from 4 weeks to 4-6 days,and may also prevent cSCC. An immunological mechanism has been demonstrated,but immunosuppressed individuals were excluded. Our feasibility study (SPOT) found 5FU superior to imiquimod cream in preventing new AK in OTR and has confirmed 5FU+CAL is preferred by patients. Aims: 1. Demonstrate that 5FU-based cream (5FU or 5FU+CAL) treatment is superior to standard of care (Sunscreen + Surveillance) in cSCC prevention in immunocompromised populations. 2. Demonstrate that the significantly shorter treatment duration for 5FU+CAL will improve tolerability and patient acceptability,improving feasibility for a long-term topical chemoprevention strategy. Methods: SPOT-IT trial is designed as a Phase III comparison of 5FU versus standard care (sunscreen) with embedded Phase II including 5FU+Cal. The trial will enrol 673 patients,who are immune compromised and have a history of at least 1 cutaneous SCC in past 5 years. Participants will be randomised 2:2:1 between standard care (n=269): 5FU (n=269): 5FU+Cal (n=135) and stratified by immunosuppression cause and number of previous cSCC. How this research will be used: If 5FU-based topical chemoprevention is shown to prevent cSCC in immunosuppressed patients,it will become standard of care for this high-risk population with a drive to develop the compounded (50:50) product leading to a phase III RCT evaluating superiority of patient preference/tolerability over 5FU. Even without a future RCT,we predict that equivalence or superiority of 5FU+Cal over 5FU will be practice changing with adoption of 5FU+Cal as first line chemoprevention for this common and morbid skin cancer.

Principal Investigator

Dr Rubeta Matin

Contact us

Email: melanie.westmoreland@ouh.nhs.uk

IRAS number

1008229