immunotherapy before transplantation for skin cancer prevention in organ transplant recipients

Conditions: Cutaneous Squamous Cell Carcinoma; Actinic Keratoses; Skin Cancer; Organ Transplant Recipients; Immunotherapy

Summary: 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).

Keywords: calcipotriol ointment 5-fu cream squamous cell carcinoma actinic keratoses organ transplant recipients prevention immunotherapy