Immunotherapy Before Transplantation for Skin Cancer Prevention in Organ Transplant Recipients

This clinical trial aims to investigate the efficacy of Calcipotriol ointment combined with 5-fluorouracil cream as an immunotherapy for actinic keratosis in Organ Transplant Recipients (OTRs) before transplantation and determine whether it can prevent cutaneous squamous cell carcinoma (SCC) in OTRs post-transplant.

The main goal of this investigator-initiated clinical trial is to determine the efficacy of topical calcipotriol combined with 5-flourouracil (5-FU) treatment in organ transplant candidates with precancerous skin lesions called actinic keratoses (AKs) with a history of skin cancer in order to prevent squamous cell carcinoma (SCC) development after transplantation. SCC is the most common cutaneous malignancy seen after transplantation, with a 65-250 fold 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. Previously, we have demonstrated the high efficacy of topical calcipotriol plus 5-FU immunotherapy for AKs on the face and scalp in significantly reducing the risk of SCC development within 3 years post-treatment 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 low calcemic vitamin D analogue that is FDA-approved for the treatment of psoriasis. Topical 5-FU is a chemotherapy that is the standard treatment for AKs. Our previous research demonstrates the synergistic impact of calcipotriol in combination with 5-FU on a robust T cell immunity against early skin carcinogenesis in immunocompetent patients. Therefore, we aim to determine the efficacy of this immunotherapy before transplantation in reducing the risk of SCC post-transplant despite the immunosuppressive medications.

Eligibility Criteria:
Inclusion Criteria:

* Solid organ transplant candidates with AKs and a history of non-melanoma skin cancer. The target population includes the patients who are undergoing kidney, lung, liver and heart transplantations.
* Presence of four to fifteen clinically typical, visible, and discrete AKs in 25 cm2 on any of the four anatomical sites: scalp, face, right upper extremity and left upper extremity.
* The period between the first visit and transplantation is minimum 4 weeks and maximum 12 months.
* Age of at least 18 years
* Ability and willingness of the patient to participate in the study (Informed consent will be obtained)

Exclusion Criteria:

* Treatment area is within 5 cm of an incompletely healed wound or a suspected basal cell or squamous cell carcinoma.
* Treatment area contained hypertrophic and hyperkeratotic lesions, cutaneous horns, or lesions that had not responded to repeated cryotherapy.
* Patients with history of hypercalcemia or vitamin D toxicity.
* Female participants must be either of non-reproductive potential (i.e., post-menopausal by history of age \> 50 years old and no menses for \>1 year without an alternative medical cause; OR history of hysterectomy, history of bilateral tubal ligation, or history of bilateral oophorectomy) OR must have a negative serum pregnancy test within 7 days prior to study registration.
* Patients with DPD (Dihydropyrimidine Dehydrogenase) deficiency (due to their higher risk of 5-FU toxicity).