Case series experience suggests expanding role for topical imiquimod

National report - Accumulating data is adding evidence to support a role for topical imiquimod 5 percent cream (Aldara, 3M Pharmaceuticals) as a secondary alternative to conventional excisional or Mohs micrographic surgery for treating various types of skin cancers in patients who are poor surgical candidates - or refuse surgery - says M. Shane Chapman, M.D., assistant professor of dermatology, Dartmouth-Hitchcock Medical Center, Lebanon, N.H.

Dr. Chapman describes his experience using topical imiquimod to treat patients with sclerotic basal cell carcinoma (sBCC) and lentigo maligna (LM).

He reports that two of three patients achieved clinical and histological clearance of sBCC after 12 weeks of once daily imiquimod treatment. The lesion in the third patient decreased in size, but had still not cleared after seven months of treatment with imiquimod daily to every other day.

The LM series consisted of 12 patients who applied topical imiquimod at varying application frequencies and durations. In most patients, imiquimod was the primary treatment, although some patients were being treated for a recurrent lesion or because of positive histologic margins after surgical excision.

All 12 patients achieved clinical clearance, and eight patients consented to punch biopsy for histological confirmation of treatment success. The specimens, taken from the most clinically suspicious area pretreatment, were clear in six patients and contained single atypical melanocytes in the remaining two.

During careful follow-up that extends up to around two years, none of the successfully treated sBCCs or LMs have recurred. In addition, Dr. Chapman tells Dermatology Times that he and his colleagues at Dartmouth have now used topical imiquimod to treat LM in more than 40 additional patients with consistent clinical success.

"Controlled clinical trials have shown imiquimod is effective for eradicating about 85 percent of superficial BCCs and about 75 percent of nodular BCCs, and there have been several case reports and small studies describing its efficacy in clearing LM. These reports from our center describe small case series of sBCC and LM, but we believe they provide additional helpful data to clinicians who are faced with treatment decisions for difficult cases," Dr. Chapman says.

However, he was cautious in noting the need for further follow-up in order to characterize the five-year recurrence rates associated with topical imiquimod treatment.

"Those data will not be available for several years, but they will allow us to compare the outcomes achieved with imiquimod against our gold standard surgical interventions and thereby more definitively evaluate if this topical treatment is an acceptable option to offer patients when there are reasons against performing surgery," he says.

Flexible dosing

Dr. Chapman notes that there is as yet no standard regimen for using topical imiquimod to treat skin cancers. For the LM patients included in the reported case series, initial treatment frequency ranged from two to seven times a week and treatment was continued for seven to 44 weeks.

However, Dr. Chapman generally prescribes a 12-week course that begins with once daily application five days a week as that protocol has performed fairly reliably in his experience. The frequency of application is titrated according to the inflammatory response and tolerability, with usage decreased if patients are uncomfortable because of the local skin reaction and increased or combined with a topical retinoid if they fail to develop an inflammatory response.

"The patient whose sBCC failed to clear had a poor inflammatory response to imiquimod, and it seems reasonable to try adding a retinoid to prime the immune system when there are no other real options for treatment. However, such combination use is anecdotal and there are no data to demonstrate regarding efficacy," Dr. Chapman says.

Biopsy preferred

After patients complete treatment with topical imiquimod, Dr. Chapman evaluates the histologic response with a punch biopsy if the patient allows, and all patients are followed clinically for recurrence, including with a Woods light examination in patients treated for LM.

"There are some who would argue that complete excision is needed to establish success in treating the skin cancer, but these are patients who often did not want surgery in the first place, and so a small biopsy may be the only option. The other side of the coin is that there remains a risk for recurrence even after standard treatment with surgery, and so regardless of how therapy is approached, careful follow-up is an essential component of care," he says.