Topical Immunotherapy Effectively Reduces Precancerous Skin Lesions

A combination immunotherapy using 2 widely available topical drugs triggered a robust immune response against precancerous skin lesions, according to a recent study.

Actinic keratosis is a precursor to squamous cell carcinoma. In a study involving patients with this disease, researchers found that the immunotherapy activated immune system T cells, which proceeded to attack the abnormal skin cells.

The findings were published in the Journal of Clinical Investigation.

“We looked at precancerous lesions on patients with sun-damaged skin,” said study co-author Lynn A. Cornelius, MD. “Most commonly found on the face, scalp, and arms, these lesions appear abnormal by visual examination and under the microscope but are not full-blown skin cancers. But because these lesions have the potential to develop into a true skin cancer, they are commonly treated. Our study shows this combination therapy is more effective and better tolerated than current treatment practices.”

The results of the study found that on average, the investigational therapy reduced precancerous skin lesions on the face by nearly 88%, compared with a 26% reduction using standard chemotherapy.

Adverse events, including skin scaling and itching, were similar among both treatments. However, patients who received the investigational therapy reported increased burning sensations and more redness, which is consistent with the immune response.

The authors noted that although it was not specifically measured, patients treated with prior conventional therapies had a decrease in discomfort and pain with the combination treatment.

The investigational therapy consists of combination topical 5-fluorouracil and calcipotriol, a synthetic form of vitamin D. Topical 5-fluorouracil alone is used to treat actinic keratosis, while calcipotriol treats psoriasis.

Prior studies have shown that mice prone to allergic inflammation are also resistant to skin cancer development. The findings suggest that overreactive immunity triggered by damage skin may have a beneficial side effect, a hyper-vigilant immune system that attacks any cancerous cells.

Other studies have also showed that the protein TSLP in the skin activates T cells, which then attack tumor cells, and calcipotriol is also known to cause the skin to produce TSLP.

“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,” Cornelius said. “In so doing, the destroyed precancerous cells release cell proteins, or antigens, and facilitate the heightened immune system to response. We compared the 2-drug formulation to 5-fluorouracil alone over a shorter application period — 4 days as opposed to 2 to 4 weeks that is typical for the standard treatment of 5-fluorouracil alone.”

For the study, researchers enrolled 132 patients with actinic keratosis, who were treated at Washington University School of Medicine in St. Louis, MO. There were 65 patients randomized to receive the combination treatment, and 67 patients in the control arm administered the standard treatment plus Vaseline petroleum jelly. The assigned cream was applied twice daily for 4 days.

At the start of the trial, patients in the investigational arm and the control arm had similar numbers of precancerous lesions on each part of the body examined. At each evaluated body site, there was an average of about 15 lesions on the face, 22 on the scalp, 14 on the right arm, and 12 on the left arm.

The results of the study showed patients in the investigational group had their facial lesions reduced by 88%, compared with 26% in the control group. The lesions on the scalp decreased by 76% in the investigational group compared with approximately 6% for the control group.

On the right arm, the investigational group saw a reduction of 69%, versus approximately 10% for the control. The left arm saw a 79% reduction in precancerous lesions in the investigational group, compared with 16% in the control group.

“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 recontact our patients to determine whether there are differences in precancerous and skin cancer rates between the 2 treatment groups.”