Topical Vitamin D3, Diclofenac or a Combination of Both to Treat Basal Cell Carcinoma
Status:
Completed
Trial end date:
2013-05-01
Target enrollment:
Participant gender:
Summary
Basal cell carcinoma (BCC) is the most frequent malignant tumor in Caucasians and the
incidence is still increasing with 3-8% each year. Since BCCs generally occur on sun-exposed
areas of the skin, the rice in incidence is mainly explained by the increasing exposure to
(intermittent) ultraviolet radiation. Surgical excision is still the standard treatment for
(micro)nodular BCCs. The costs as well as the increased workload are stressing the health
care system even further and posing BCC an important health care problem. Since half of the
BCCs arise primarily on the face & (bald) head and treatment by surgical excision may result
in disfiguring scars, patients often experience a dramatic decrease of their quality of life.
Hence, there is an urgent medical and societal need for a simple and cheap (targeted)
treatment, preferably to be performed by the patients themselves. This treatment must be safe
and effective. Such treatment is not available yet. BCC tumorigenesis is complex and must be
multifactorial. Genetic alterations of multiple components of the Sonic Hedgehog (SHH)
pathway are involved in sporadic BCC pathogenesis; inactivating mutations in Patched-1
(PTCH1) and activating mutations of Smoothened (SMO) and Suppressor of Fused (SU(FU)). With
this knowledge, inhibition of the SHH pathway by SMO antagonists was successfully
administered, however treatment resulted only in partial clinical response ofBCC. Recently,
involvement of the Wingless (Wnt) pathway has been proven to be essential in BCC tumorigenic
response. Moreover, a recent study of our own department provides the first evidence that
epigenetic alterations, particularly promoter hypermethylation, influence both the SHH and
Wnt pathway (own data, not published), which can serve as therapeutic targets. Both
non-steroidal anti-inflammatory drugs (NSAlDS) and vitamin D derivatives are able to directly
or indirectly target the Wnt pathway. Furthermore, vitamin D3 is able to inhibit Smoothened
(SMO) in vitro, resulting in inhibition of the SHH pathway. Although in vivo studies are
lacking, the investigators assume that topical application of these drugs may inhibit BCC
growth and/or may cure BCC and thus might provide very promising future perspectives.
Calcitriol and NSAlDs ointments are both already available for other indications and save in
use. Eventually, our approach may result in a systematic approach to BCC, targeting
(epi)genetic changes to treat and/or prevent further tumour growth.
Phase:
Phase 2
Details
Lead Sponsor:
Maastricht University Medical Center
Treatments:
Calcitriol Cholecalciferol Diclofenac Ergocalciferols Vitamin D Vitamins