Patients with actinic keratosis, a precursor of a type of skin cancer called squamous cell carcinoma, may markedly benefit from the combination of two topical drugs that have been used in the clinic for several years, according to a new study published in the Journal of Clinical Investigation.
The study, “Randomized trial of calcipotriol combined with 5-fluorouracil for skin cancer precursor immunotherapy,” shows that the psoriasis topical drug calcipotriol works synergistically with a topical formulation of the chemotherapy drug 5-fluorouracil (5-FU) to induce strong immune responses against these premalignant lesions, significantly decreasing their number.
In previous studies, researchers had shown that patients with allergic skin inflammation were protected from skin cancer. This effect is thought to be caused by the release of a protein called TSLP by the defective skin, which recruits T-cells and mounts robust anti-tumor responses.
The FDA-approved topical medication for psoriasis, calcipotriol, was known to induce TSLP expression, suggesting that this drug could be used as a novel immunotherapeutic approach for cancer.
The Phase 1 study (NCT02019355) enrolled 132 patients with actinic keratosis who were randomized to receive the standard 5-FU chemotherapy plus vaseline or 5-FU in combination with calcipotriol. The cream with the drug combination was applied twice daily for four days.
“The idea behind this study was to induce a heightened immune response in the skin using calcipotriol combined with the 5-fluorouracil that works to destroy the precancerous cells,” Lynn A. Cornelius, MD, Washington University dermatologist and director of the Division of Dermatology, said in a press release.
“In so doing, the destroyed precancerous cells release cell proteins, or antigens, and facilitate the heightened immune system to respond. We compared the two-drug formulation to 5-fluorouracil alone over a shorter application period — four days as opposed to two to four weeks that is typical for the standard treatment of 5-fluorouracil alone.”
At the beginning of the study, patients in both groups had similar numbers of precancerous lesions on each of the examined parts of the body; face, scalp, right arm and left arm. Following treatment, the group assigned to the investigational drug showed major improvements compared to those who received standard therapy.
Indeed, while the number of lesions in the face, scalp, right arm, and left arm of patients in the calcipotriol group were reduced by 88%, 76%, 69%, and 79%, respectively, those on the control group showed reductions of only 26%, 6%, 10%, and 16%, respectively.
Patients receiving the experimental therapy reported more redness and increased burning sensations, which were likely caused by the immune response triggered by the treatment. Importantly, the researchers also reported that patients who had already received pior therapies had reduced pain and discomfort when treated with the combination treatment.
“Because calcipotriol has been shown to induce an immune response, we are now interested in seeing if the anti-tumor immunity of the activated T-cells can be recalled later to help prevent both precancerous and cancerous skin lesions,” Cornelius said. “We are now planning to re-contact our patients to determine whether there are differences in precancerous and skin cancer rates between the two treatment groups.”