The main goal of this investigator-initiated clinical trial is to determine the efficacy of topical calcipotriol combined with 5-fluorouracil (5-FU) treatment in OTRs on immunosuppressive medications with precancerous skin lesions called actinic keratoses (AKs) and a history of non-melanoma skin cancer in order to eliminate AKs and prevent squamous cell carcinoma (SCC) development. SCC is the most common cutaneous malignancy seen after transplantation, with a 65-250fold greater incidence in organ transplant recipients (OTRs) compared to the general population. This increased risk is due to the systemic immunosuppression caused by anti-rejection medications, which are indispensable for protecting against allograft loss. Our previous findings have established the efficacy of calcipotriol in combination with 5-FU in inducing an antitumor immunity against AKs in immunocompetent patients. This SCC risk reduction is accompanied by the induction of robust T cell immunity and TRM cell formation against AKs. Calcipotriol is a FDA-approved low calcemic vitamin D analogue for the treatment of psoriasis. Topical 5-FU is a standard chemotherapy for AKs. Based on our previous findings demonstrating the synergistic impact of TSLP induction by calcipotriol in combination with the cytotoxic effects of 5-FU that leads to a robust T cell immunity against early skin carcinogenesis in immunocompetent patients, we aim to determine whether this efficacy is maintained in OTRs on immunosuppressive therapy and its effect on SCC prevention in long-term after transplantation.
This clinical trial aims to investigate the efficacy of Calcipotriol ointment combined with 5-FU cream in Organ Transplant Recipients (OTRs) to determine if it can stimulate the immune cells against actinic keratoses precancerous skin lesions after transplantation and prevent cutaneous squamous cell carcinoma (SCC) in long-term.