Research on Immunotherapy and Chemotherapy for Skin Cancer Prevention

Overview of Skin Cancer Risk

Researchers have assessed a combined immunotherapy and chemotherapy cream aimed at preventing skin cancer after precancerous lesions occur on sun-damaged skin. Despite a general understanding of the importance of sun protection, squamous cell carcinoma (SCC) remains the second most prevalent cancer in the United States, with its incidence on the rise. Skin cancer, along with its treatment, can lead to significant disfigurement and pose life-threatening risks. Thus, preventing sun damage and effectively treating precancerous skin lesions is crucial in avoiding the progression to SCC.

Importance of Treating Precancerous Skin Lesions

The study, conducted by researchers at Washington University in St. Louis, demonstrated that a topical cream combining the chemotherapy agent 5-Fluorouracil (5-FU) and the immunotherapy drug calcipotriol—an artificial form of vitamin D—was more effective in clearing actinic keratoses (precancerous skin lesions) than the standard treatment with 5-FU alone. The mechanism behind this involves calcipotriol activating T cells in the immune system, which target and eliminate precancerous cells. The researchers further explored whether this combination therapy could also prevent the future occurrence of SCC by fostering immune system “memory” cells, with their findings recently published in JCI Insight.

Study Design and Findings

Clinical Trial Overview

In the initial phase of the study, 130 patients with actinic keratoses were randomly divided into two groups: one received a four-day treatment of 5-FU combined with calcipotriol (combination treatment group), while the other group received only 5-FU cream (standard treatment group). Following the treatment, the effectiveness of both therapies in clearing actinic keratoses was evaluated, and the participants were monitored for three years to track the incidence of both SCC and basal cell carcinoma (BCC), another skin cancer variant.

Results of the Three-Year Follow-Up

The researchers successfully gathered three-year follow-up data for over half of the initial trial participants. The results indicated that significantly fewer patients in the combination treatment group developed SCC on the face and scalp compared to those in the standard treatment group. However, no notable difference was observed in the incidence of SCC on the arms or the development of BCC between the two groups.

Conclusions and Implications

The research concluded that the combination therapy not only cleared actinic keratoses more effectively but also reduced the risk of developing SCC on the face and scalp over a three-year period when compared to the standard treatment. Dr. Shawn Demehri, a lead author of the study, stated, “This finding provides the first clinical proof-of-concept that immunotherapy directed against premalignant tumors can prevent cancer.”

The researchers speculated about the lack of difference in SCC development on the arms, suggesting that the topical immunotherapy may penetrate the skin of the face and scalp more effectively, thus triggering a stronger immune response in those areas. They also acknowledged that the short duration of treatment (administered twice daily for four days) could be a factor, indicating that longer treatment durations may be necessary for the skin on the arms and other body areas.

References

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.