Topical calcipotriol and 5-fluorouracil combination effective against skin cancer precursor
Researchers from the US recently demonstrated synergistic effects of topical calcipotriol and 5-fluorouracil (5-FU) for the treatment of actinic keratosis, a known precursor to squamous cell carcinoma (SCC) of the skin.
Twice-daily use of 0.005 percent calcipotriol ointment plus 5 percent 5-FU cream for 4 days resulted in a higher actinic keratosis reduction rate on the face (88 vs 26 percent), scalp (76 vs 6 percent), right upper extremity (69 vs 10 percent) and left upper extremity (79 vs 16 percent) at 8 weeks after treatment vs twice-daily petroleum jelly plus topical 5-FU (p<0.0001 for all anatomical sites). [J Clin Invest 2016, doi: 10.1172/JCI89820]
The randomized, double-blind study was conducted on 131 patients for 17 months at Washington University Medical Center, St. Louis, Missouri, US. Sixty-five of these patients received the investigational topical combination therapy, whereas 67 served as the control group and received topical 5-FU added to petroleum jelly as vehicle.
5-FU is a thymine analogue that kills cancer cells by inducing programmed cell death and is proven to be efficacious for the treatment of actinic keratosis. Calcipotriol, a synthetic derivative of vitamin D, is approved by the US FDA for the treatment of psoriasis. [Immunotherapy 2012;4:939-945; http://www.fda.gov/downloads/Drugs/.../Guidances/UCM224144.pdf]
“Actinic keratosis has the potential to develop to SCC of the skin. Hence, they are commonly treated. We believe our recent findings establish the combination of topical calcipotriol and 5-FU as a novel treatment for actinic keratoses that can potentially prevent skin cancer development,” the authors said.
“The mechanism of action of this combination therapy involves induction of CD4+ T cell immune response with elaboration of the cytokine, thymic-stromal lymphopoietin, against actinic keratoses. This necessitates an intact immune system, and the activity against actinic keratosis actually resembles skin graft rejection,” they explained.
Minor adverse effects were observed with the combination treatment. More patients who received topical calcipotriol plus 5-FU vs the control group experienced skin redness (69 vs 25 percent; p<0.0001), burning skin sensation (39 vs 13 percent; p=0.0008), and delayed erythema resolution pattern after treatment (91 vs 6 percent; p<0.0001).
Actinic keratosis and SCC incidence rates have seen an increasing trend among the Asian population. SCC is the second most common skin cancer in the Chinese and Japanese, accounting for 30 percent of all skin cancers in Japan. The incidence rate of SCC in the Chinese population was reported to be 2.6–2.9 per 100,000. [J Clin Aesthet Dermatol 2009;2:39-42]
“The short treatment duration and minimal side effect profile highlight the advantages of topical calcipotriol plus 5-FU as an optional treatment for patients with actinic keratosis compared with the currently approved treatments,” the authors concluded.