Two topical drugs that have been used for years, trigger a robust immune response against precancerous skin lesion when used together. The research, from Washington University
School of Medicine in St. Louis and Harvard Medical School, shows that
the therapy activates the immune system's T cells, which then attack the
abnormal skin cells.
‘The immunotherapy destroys precancerous cells which release cell proteins, or antigens, and facilitates the heightened immune system.’
looked at precancerous lesions on patients with sun-damaged skin," said
Washington University dermatologist and study co-author Lynn A.
Cornelius, MD, director of the Division of Dermatology. "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
involved 132 patients with actinic keratosis 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
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.
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.
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. 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.
Interestingly, although not specifically measured, patients who had been
treated previously with conventional therapies reported decreased pain
and discomfort with the combination treatment, according to Cornelius,
who is also the Winfred A. and Emma R. Showman Professor of Dermatology.
investigational treatment combines a cream formulation of a
chemotherapy drug called 5-fluorouracil with a synthetic form of vitamin
D called calcipotriol. Topical 5-fluorouracil alone is prescribed to
treat actinic keratosis. Calcipotriol is approved by the Food and Drug
Administration (FDA) for treatment of psoriasis, an autoimmune disorder
characterized by red, scaly patches of skin.
Past studies of mice
prone to allergic inflammation, especially eczema rash on the skin, have
shown that they also are resistant to developing skin cancer. These
observations suggested that overreactive immunity triggered by damaged
skin may have a beneficial side effect — a hyper-vigilant immune system
that also attacks any cancerous cells that may form. Earlier work at
Washington University by senior author Shadmehr Demehri, MD, PhD, now at
Harvard Medical School, 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.
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 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."
"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