New Combo Therapy Beats Out Gold Standard Treatment For AKs

Combining a cream formulation of 5-fluorouracil with a synthetic form of vitamin D called calcipotriol may trigger a robust immune response against actinic keratosis, according to research out of rom Washington University School of Medicine in St. Louis and Harvard Medical School in Boston.  

Topical 5-fluorouracil alone is prescribed to treat actinic keratosis. Calcipotriol is approved by the Food and Drug Administration (FDA) for treatment of psoriasis.

The new research, published Nov. 21 in The Journal of Clinical Investigation, shows that the combination therapy activates the immune system’s T cells.

On average, the investigational therapy reduced the number of precancerous skin lesions on the face by almost 88 percent compared with a 26 percent reduction using the standard chemotherapy, the study showed. "Our study shows this combination therapy is more effective and better tolerated than current treatment practices," says Washington University dermatologist and study co-author Lynn A. Cornelius, MD, director of the Division of Dermatology. 

While some side effects such as skin scaling and itching were similar with both treatments, patients receiving the investigational therapy reported more redness and increased burning sensations, which are consistent with the immune response it triggers.  Patients who had been treated previously with conventional therapies reported decreased pain and discomfort with the combination treatment, according to Dr. Cornelius, who is also the Winfred A. and Emma R. Showman Professor of Dermatology.

Earlier work at Washington University showed that a protein called TSLP in the skin activates the immune system's T cells, which then attack tumor cells. Calcipotriol also was known to cause the skin to produce TSLP.

The current study involved 132 patients with actinic keratosis who were treated at Washington University School of Medicine in St. Louis. Sixty-five of these patients were randomly assigned to receive the investigational drug combination of 5-fluorouracil plus calcipotriol. The remaining 67 served as a control group and received the standard 5-fluorouracil plus Vaseline petroleum jelly. Patients applied the assigned cream twice daily for four days.

Patients in the investigational and control groups began the trial with similar numbers of precancerous lesions on each part of the body examined. At each body site evaluated, there were on average about 15 lesions on the face, 22 lesions on the scalp, 14 lesions on the right arm and 12 on the left arm. Following treatment, facial lesions were reduced by 88 percent in the investigational group versus 26 percent in the control group. On the scalp, lesions were reduced by 76 percent in the investigational group compared with about 6 percent for the control group. On the right arm, the reduction was 69 percent for the investigational treatment versus about 10 percent for the control. On the left arm, the precancerous lesions were reduced by 79 percent for the investigational treatment compared with 16 percent for the control.

"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 says in a news release. "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."

CAPTION: Washington University dermatologist Lynn Cornelius, MD, (left) conducts a skin exam with patient Robert Manchester. Manchester is a participant in a clinical trial testing the effectiveness of a new topical immunotherapy against precancerous skin lesions called actinic keratosis, often found on sun-damaged skin.

PHOTO CREDIT: Image courtesy of Washington University in St. Louis