New research indicates that topical imiquimod has potential for treating conditions ranging from Bowen's disease to leishmaniasis. Problems with inflammation and recurrences of conditions such as actinic keratosis, however, are still being investigated.
Meanwhile, case reports for another important indication - the treatment of Bowen's disease - are now backed up by more substantive evidence. A study taking a retrospective look at the off-label treatment of the condition with imiquimod found that 86 percent of 49 patients had a complete response to the treatment.
With follow-up duration ranging from one to 44 months, 14 percent of the subjects failed therapy and required additional treatments. (Dermatol Surg. 2007 Apr;33(4):427-431; discussion 431-432).
"Nobody had ever treated that many patients with imiquimod, so it was groundbreaking to do so and demonstrate efficacy with up to four years' follow-up."
The issue of the follow-up period is particularly significant, since one of imiquimod's caveats is the possibility of recurrences, and experts currently say the need for follow-up evaluation should extend for at least five years.
"A problem is that imiquimod may not 'cure' things over the long haul," says Dr. Rosen, chief of the VA Dermatology Clinic and professor in the department of dermatology at the Baylor College of Medicine here.
"For example, about 10 percent of BCCs thought to be cured will recur when patients are followed from two to three years," Dr. Rosen says.
Physicians can get a false sense of security from the drug and neglect that important follow-up, he says.
"The problem is imiquimod might be used as a replacement for judgment and biopsy, and some may think, 'If it kills all kinds of skin cancer, it doesn't matter what I'm dealing with, I'll just use Aldara (Graceway Pharmaceuticals)' - and that is a dangerous thinking pattern," Dr. Rosen tells Dermatology Times.
Joel Schlessinger, M.D., agrees that, despite a cure rate of basal cell carcinoma in the 80 percent range that led to the drug's approval, physicians still face a strong element of uncertainty due to significant false positives and false negatives.
"This is the quintessential challenge with Aldara, but hopefully, this will be addressed as more research is done on this unique compound," Dr. Schlessinger says.
The suggestion of a stronger dose than the current 5 percent strength likely wouldn't be a sound solution to the problem, and could only introduce more complications, Dr. Rosen says.
"Dose-ranging studies demonstrated early on that the current percentage is sufficient for clinical benefit with associated but tolerable side effects," he says. "A higher percentage might also increase the risk of systemic interferon release to the point where an uncomfortable flu-like reaction would become more common (instead of uncommon, as it is now)."
Imiquimod currently has Food and Drug Administration (FDA) approval for treatment of anogenital warts, actinic keratosis (AK) and superficial basal cell carcinoma (SBCC), and while efficacy rates for such uses are impressive, they are not all that much higher than alternative therapies, such as liquid nitrogen for AKs or excision for SBCCs.
Key benefits that imiquimod offers over other treatments include a much better cosmesis compared with something like liquid nitrogen for AKs, and usefulness as an alternative for elderly patients or others who are not surgical candidates for nonmelanoma skin cancers.
But while imiquimod is particularly appropriate for field treatment over a broad area, that paradoxically means more of an area for irritation, says Dr. Schlessinger, director of the Advanced Skin Research Center, Omaha, Neb.
"The biggest limitation in using Aldara on actinic keratoses is the fact that the worse the involvement, the more likely the patient is to be terribly uncomfortable during treatment," he says.
Problems with discomfort can range from crusting and blistering to inflammation and erosion.
"The reality is that liquid nitrogen is pretty impressive in practice, and is fairly easy to administer with an excellent improvement," he says "The downside to liquid nitrogen is that what you see is what you get as far as improvement, while Aldara provides a more impressive result, both initially and subsequently.
"Unfortunately, however, most patients don't have the will or desire to look that rough for weeks on end, so the results aren't worth it for them, and that is why my patients usually opt for liquid nitrogen," Dr. Schlessinger says.