WASHINGTONImiquimod (Aldara), an immune response
modifier used to treat genital warts, provided effective therapy for both
actinic keratosis and primary superficial basal cell carcinoma in pilot studies
presented at the 59th Annual Meeting of the American Academy of Dermatology.
Eggert Stockfleth, MD, Department of Dermatology, University of
Kiel, Germany, said that actinic keratosis is a premalignant skin condition
that progresses to squamous cell carcinoma in 6% to 10% of patients.
Locally occurring, primary superficial basal cell carcinoma, is
the most common skin cancer and accounts for more than a million new cases each
year, said John K. Geisse, MD, assistant clinical professor of dermatology and
pathology, University of California, San Francisco.
Current treatments have been effective in the clearance of
actinic keratosis lesions, but therapy can be painful, may create scarring, and
destroys some healthy tissue, Dr. Stockfleth said. Options include cryosurgery
with liquid nitrogen to "burn off" affected tissue and fluorouracil
(5-FU), a topical agent that can cause pain and significant local reactions.
5-FU has been shown to be successful in up to 80% of cases; however, 1-year
recurrence rates of more than 50% make it a less than optimal therapy.
The standard treatment for primary basal cell carcinomas is
surgical excision of the affected area. While the surgical cure rate is 90%,
scarring is an inevitable consequence, Dr. Geisse said.
Imiquimod stimulates the body to produce cytokines, including
interferon, that enhance cell-mediated immunity, a natural process by which the
body controls or eliminates virus-infected cells or tumor cells.
In two phase II pilot studies of imiquimod in basal cell
carcinoma, prestudy biopsies of less than 25% of the affected areas were taken
for histologic examination to confirm diagnosis and for comparison after the
study, Dr. Geisse said. Patients were then randomized to either placebo or
imiquimod 5% cream at various application frequencies.
At the conclusion of the studies, one of 6-weeks’ duration
with 99 patients and the other lasting 12 weeks with 128 patients, affected
areas were excised and subjected to thorough microscopic examination.
The study results showed cure rates of 87% (27 of 31 patients)
and 88% (29 of 33 patients) for once-a-day application in the 6-week and
12-week studies, respectively, which is comparable to current surgical cure
rates, Dr. Geisse reported.
Adverse events were reported by 81% and 67% of patients in the
two respective studies. Erythema (42% and 27%, respectively) and scabbing (29%
and 24%, respectively) were the most common investigator-assessed reactions.
Twice-daily dosing was not well tolerated and was discontinued in both studies.
Actinic Keratosis Study
In Dr. Stockfleth’s study, 37 patients with biopsy-proven
actinic keratosis were randomized to either placebo or active treatment with
application of imiquimod 5% cream to the affected area three times a week for
The results showed that imiquimod-treated lesions were cleared
clinically and histologically in 87.5% of patients, while no clearance was seen
in the placebo group. Two of the three imiquimod-treated patients who did not
achieve complete resolution showed more than 75% clearance of their skin
"We have more than 3 years of data and experience with
imiquimod, and most of our patients show no recurrence," Dr. Stockfleth
Of the 22 patients assigned to treatment with imiquimod, five
withdrew, none due to adverse reactions. Adverse reactions occurred in 88% of
patients (15 of 17), with irritation (59%) and redness (24%) most commonly
cited. These reactions were mild to moderate in nature, Dr. Stockfleth said.
Although 71% of patients (12 of 17) required rest periods
averaging 2 weeks in length, all finished the 8-week treatment and 8-week
"The early data suggest a real potential for use in daily
practice," Dr. Geisse commented. Pending further investigations, he said,
imiquimod cream would give physicians and patients a new treatment modality for
both actinic keratosis and primary superficial basal cell carcinoma that is
nonsurgical and can be administered at home without postsurgical scarring.
Phase III trials of imiquimod in actinic keratosis and basal
cell carcinoma are planned, the researchers said. The studies were sponsored by
3M Pharmaceuticals (St. Paul, Minnesota), manufacturer of imiquimod.