The third topical agent used, tretinoin, is known to interfere with carcinogenesis and apoptosis. It is a retinoid, or a vitamin-A derivative, that acts on nuclear retinoic acid receptors in order to control cellular proliferation and differentiation.15 Topical tretinoin has been studied for its potential role as a chemopreventive agent for BCC and SCC, but thus far has been proven ineffective . One study in renal transplant patients, with increased risk for SCC, showed that a combination of topical tretinoin and low dose systemic retinoids, in an attempt to lessen toxicity associated with high dose systemic retinoids, reduced the number of existing SCCs and reduced risk of new SCCs.25 While efficacy of topical tretinoin as monotherapy for SCC has not been studied, a combination of topical tretinoin, imiquimod and 5-FU, each with their distinct mechanisms of action, may provide improved long-term tumor free survival compared to single-drug regimens for patients with invasive SCC.
We present a patient with invasive SCC successfully treated with combination topical therapy consisting of 5% imiquimod cream, 2% 5-FU solution, and 0.1% tretinoin cream. Previous reports of the use of single-drug topical therapy with imiquimod or 5-FU in the treatment of SCC in situ shown promising results, however the success rates were still lower than surgical management. We demonstrate that the combination of these three medications provided an excellent outcome in our case, although the follow-up was only 25 months. Prospective randomized clinical trials are needed to support these findings, which may offer patients a non-surgical alternative to the current standard of care.
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