Clinical Potential for Vitamin D as a Neoadjuvant for Photodynamic Therapy of Nonmelanoma Skin Cancer

摘要

Nonmelanoma skin cancer (NMSC), comprising basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), is the most common form of human cancer worldwide. Effective therapies include surgical excision, cryotherapy, and ionizing radiation, but all of these cause scarring. ALA-based PDT is a non-scarring modality used routinely for NMSC in Europe but not in the USA, primarily due to lingering uncertainties about efficacy. We have identified three agents (methotrexate, 5-fluorouracil, and vitamin D) that can be used as neoadjuvants, i.e., can be given as a pretreatment prior to ALA-PDT, to improve the efficacy of tumor killing in mouse models of NMSC. Vitamin D (VD3) is the most recent neoadjuvant on this list. In this presentation we make the case that VD3 may be superior to the other agents to improve results of ALA-PDT skin cancer treatment. The active form of VD3 (calcitriol) is available topically as a pharmaceutical grade cream or ointment (FDA-approved for psoriasis), and works well for boosting ALA-PDT tumor treatment in mouse models. For deep tumors not reachable by a topical route, calcitriol can be given systemically and is very effective, but carries a risk of causing hypercalcemia as a side effect. To circumvent this risk, we have conducted experiments with the natural dietary form of VD3 (cholecalciferol), and showed that this improves ALA-PDT efficacy almost to the same extent as calcitriol. Because cholecalciferol does not increase serum calcium levels, this represents a potentially extremely safe approach. Data in mouse models of BCC and SCC will be presented.