Immune response modifier post-op

San Francisco - Results from several studies performed with imiquimod 5 percent cream (Aldara, 3M Pharmaceuticals) suggest that the immune response modifier may have a role as a surgical adjuvant for improving local tumor control and/or to enhance scar appearance, says James M. Spencer, M.D., M.S., clinical professor of dermatology, Mt. Sinai School of Medicine, New York.

"Imiquimod is currently approved for treating external genital warts, actinic keratoses and superficial basal cell carcinomas, and its efficacy in clearing those lesions is a result of its ability to upregulate the expression of a diverse cocktail of cytokines.

Based on its mechanism, imiquimod can also be theorized to have a variety of other potential uses that may include enhancing elimination of residual tumor present after a primary surgical intervention and modulating wound healing," Dr. Spencer explains.

Results of a study published several years ago by Naylor et al. [Br J Dermatol 2003;149(Suppl 66):66-70] indicated that topical imiquimod was effective as primary therapy in the vast majority of cases where it was used for the treatment of histologically-confirmed lentigo maligna.

In that report, 26 of 28 patients who applied imiquimod daily for three months achieved a complete response.

Dr. Spencer notes surgical excision remains the standard of care for treatment of lentigo maligna. However, considering that approach is associated with a significant local recurrence rate of 10 percent to 20 percent, the results achieved using imiquimod as primary therapy suggest it might have a role for postsurgical application in order to improve local tumor control, says Dr. Spencer, who is also in private practice in St. Petersburg, Fla.

Following oncology's lead

"Dermatologists have a tendency to treat malignant lesions with a single modality whereas our colleagues in medical and surgical oncology combine interventions.

"Although the results achieved with primary imiquimod therapy for lentigo maligna are encouraging, it is a small study and does not support a change in conventional treatment. On the other hand, while efficacy of using imiquimod post-surgery to reduce lentigo maligna recurrence has not been proven, I consider that application in the 'why not' category based on assessment of its potential benefits and minimal downsides," Dr. Spencer explains.

In his own study, Dr. Spencer investigated whether application of imiquimod following curettage and electrodesiccation (C&D) for the treatment of nodular basal cell carcinoma (BCC) might reduce the risk of residual cancer (Dermatol Surg 2006;32:63-69).

"Histologic studies show that residual cancer can be found in 20 percent to 40 percent of specimens excised immediately after C&D, and, yet, the five year recurrence rate for these tumors is less than 10 percent. Various authors have suggested that a post-treatment immune response explains the difference. If that is the case, it seems reasonable to use imiquimod post-C&D to promote an immune response to residual tumor," Dr. Spencer explains.

He performed C&D in 20 patients with nodular BCCs at various anatomic locations, and randomized them to post-C&D treatment with topical imiquimod or vehicle applied onto the wound once nightly for four weeks.

Four weeks following the end of the topical treatment, he excised the area for histological evaluation. The specimens were positive for residual cancer in four of 10 specimens from the placebo group compared with only one of 10 treated with imiquimod.

Complementing conventional treatments

"C&D continues to be the most widely used method for treating nodular BCC in the U.S.

"The results of this small study suggest imiquimod may have an adjuvant role, although further investigations are warranted to investigate its benefits for reducing the risk of recurrence," Dr. Spencer says.

His study also included evaluations of healing responses. Although imiquimod significantly delayed wound healing, all of the wound sites were healed at eight weeks post-C&D. However, scar appearance was superior in patients who had applied imiquimod.