Imiquimod Cream Studied in Skin Cancers

WASHINGTON—Imiquimod (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 12 weeks.

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 lesions.

"We have more than 3 years of data and experience with imiquimod, and most of our patients show no recurrence," Dr. Stockfleth said.

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 follow-up.

"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.