MIAMI — The topical immune response modulator imiquimod has a role in the treatment of melanoma in situ, particularly if patients refuse or fail surgery.
There are several concerns. The agent is only recommended for thinner lesions, and "failures do occur," said Dr. M. Shane Chapman of Darmouth-Hitchcock Medical Center in Lebanon, N.H. Also, "the 5-year follow-up data is not great—it's sparse. We are just not there yet."
Despite this, he said, imiquimod 5% cream (Aldara, Graceway) can have a role in the management of melanoma in situ, also known as lentigo maligna. Dr. Chapman acknowledged the controversial nature of his stance, and based his position on small case series, one "good prospective study" in the literature, and his own experience with more than 60 patients.
As an example, he discussed a 36-year-old man with metastatic melanoma. The patient had multiple surgeries and radiation therapy "and nothing seemed to work," he said. "I basically bathed him in imiquimod over several months." Six years later, the patient is doing well with no signs of nodal or metastatic disease. As with all melanoma patients, regardless of the therapy, they should be followed continuously for a lifetime, he said at the annual meeting of the American Academy of Dermatology.
In his regimen, imiquimod 5% cream is applied five times per week for 12 weeks, with a rest period on weekends. Inflammation can be intense with this aggressive protocol, so it is important to educate patients beforehand. Pretreatment with retinoids—such as tazarotene (Tazarac, Allergan) for 2 weeks—can increase the effectiveness of imiquimod in this setting, he added.
"The only good prospective study to date," Dr. Chapman said, is an open-label trial in which participants received daily treatment with topical 5% imiquimod for 3 months, followed by a biopsy 1 month post therapy (Br. J. Dermatol. 2003;149:66-70). The complete response rate was 93% in 28 patients with histologically confirmed lentigo maligna. Two patients were treatment failures.
Because of potential failures, "always go back and do a biopsy after clearance," he said.
For example, in a retrospective study of 40 patients pretreated with imiquimod (Dermatol. Surg. 2008;34:147-51), 30 appeared clinically clear after staged excision "but three of these had histologic evidence of disease—that is why I always do a follow-up biopsy."
One of his own patients failed after initial clearance of his lesion, Dr. Chapman said. The man had a large scalp lesion that cleared following use of topical imiquimod without retinoid treatment. "For 8 months, we thought he was cleared. He came back and had a node in middle of the lesion site—his third recurrence over 5 years." Dr. Chapman added, "He's doing well, but failures do occur."
It is important to realize that "we think we know when something is in situ, but we don't always know the entire lesion is in situ when we do this," Dr. Chapman said.
Even though surgical excision remains the first-line choice for most patients with melanoma in situ or thin melanoma lesions, surgery nonresponders or those who refuse resection can benefit from imiquimod. He cited three examples: a woman who did not want to have repeat surgery and whose lesion cleared with imiquimod; a man who did not want further surgery following two melanoma lesion excisions close together on his temple, who was treated well with imiquimod; and a patient with recurrent melanoma in situ at the forehead flap of the nose who is doing well 4 years out after imiquimod treatment.
In response to a question from the audience, Dr. Chapman said, "I don't think just any inflammatory response is going to make melanoma go away. Imiquimod is one of those serendipitous chemicals that is useful for a lot of skin tumors for some reason."
Dr. Chapman is a consultant for, and receives honoraria from, Graceway. He also receives honoraria from Abbott.