Researchers evaluated an immunotherapy-chemotherapy combination cream in the prevention of skin cancer following precancerous lesions in sun-damaged skin.
Despite widespread awareness of the need to protect skin from the sun, squamous cell carcinoma (SCC) of the skin is the second most common cancer in the United States, and its incidence continues to rise. Skin cancer and its treatment can be disfiguring and life-threatening. It is important to prevent sun damage and give effective treatment to precancerous skin lesions that could develop into SCC.
Prevention and effective treatment of precancerous skin lesions are essential
Researchers at Washington University, St. Louis, USA, already showed that a topical cream treatment with a combination of the chemotherapy drug 5-Fluorouracil (5-FU) plus the immunotherapy drug calcipotriol (a synthetic type of vitamin D) can clear precancerous skin lesions – called actinic keratoses – more effectively than the standard treatment with 5-FU cream alone.
They found that the immunotherapy agent calcipotriol activates the immune system’s T cells, which attack precancerous cells. The researchers have now investigated whether this combination treatment also prevents future development of SCC, by inducing immune system “memory” cells. They recently published their findings in JCI Insight.
In the initial study, the researchers randomly assigned 130 patients with actinic keratoses to receive a four-day treatment course with either 5-FU plus calcipotriol cream (combination treatment group) or 5-FU cream alone (standard treatment group). After comparing the two treatments’ effectiveness in clearing actinic keratoses, the patients were followed up for three years to assess the incidence of SCC and basal cell carcinoma (BCC), another type of skin cancer.
Topical immunotherapy reduced risk of skin cancer developing from precancerous lesions
The researchers collected three-year follow-up data for more than half of the original trial group. Significantly fewer patients in the 5-FU plus calcipotriol combination group developed SCC on the face and scalp than in the 5-FU alone standard treatment group. There was no difference between the two treatment groups in the development of SCC on the arms, or in the development of BCC.
The researchers concluded that, in addition to clearing actinic keratoses more effectively, a short course of combination topical 5-FU plus calcipotriol lowered the risk of developing SCC on the face and scalp at three years compared to standard treatment. “This finding provides the first clinical proof-of-concept that immunotherapy directed against premalignant tumors can prevent cancer,” commented Dr. Shawn Demehri, a lead author on the study.
Speculating as to why there was no difference between the treatment groups in the development of SCC on the arms, the researchers suggested that the topical immunotherapy cream may penetrate the skin of the face and scalp more easily and induce a stronger immune response in those areas. They also noted that the treatment course was relatively short (twice daily for four days), and longer treatment may be needed on the skin of the arms and other parts of the body.
Written by Julie McShane, Medical Writer
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- Rosenberg AR, Tabacchi M, Ngo KH et al. Skin cancer precursor immunotherapy for squamous cell carcinoma prevention. JCI Insight 2019;4(6):e125476. DOI:10.1172/jci.insight.125476
- Washington University School of Medicine, Press release 21 March 2019. “Topical immunotherapy keeps skin cancer risk at bay” https://www.eurekalert.org/pub_releases/2019-03/wuso-tik031919.php