Imiquimod effective for many skin cancers, expert says
EXPERT ANALYSIS FROM THE ANNUAL MEETING OF THE CALIFORNIA SOCIETY OF DERMATOLOGY AND DERMATOLOGIC SURGERY SANTA BARBARA, CA, USA - Imiquimod should be considered a possible treatment option for most skin cancer patients, according to Dr. Craig Kraffert. Currently, imiquimod is approved only for the treatment actinic keratoses and basal cell carcinoma (BCC), but its greatest therapeutic benefit may occur with off-label use, Dr. Kraffert said at the annual meeting of the California Society of Dermatology and Dermatologic Surgery. "It’s reasonable to consider for all basal cell carcinoma subtypes, but it’s not for aggressive or large squamous cell carcinoma, and it’s certainly not for invasive melanoma," said Dr. Kraffert, who practices dermatology in Redding, CA, USA. Advantages to using imiquimod, he said, include the fact it doesn’t require surgery, it has a good cure rate, noncures are identifiable, and it causes minimal scarring "Disadvantages are that it’s time consuming, there’s transient morbidity, and it requires a coherent, compliant patient as well as provider oversight," he said. "And it’s a bit expensive." In his practice, he uses imiquimod for patients with al types of BCC, for those with in situ and superficially invasive squamous cell carcinoma (SCC), and for those with melanoma in situ. "It’s also good for premalignant epithelial targets such as actinic keratoses, actinic cheilitis, vulvar intraepithelial neoplasia, vaginal intraepithelial neoplasia, and oral leukoplakia," he said. "Imiquimod therapeutic considerations for malignant and premalignant processes can be considered essentially equivalent." He presented clinical data from patients in his practice who have been treated with imiquimod to date. Of 50 patients with SCC in situ, 70% had success with combination therapy, 28% had success with monotherapy, and 2% discontinued therapy. Of 328 patients with BCC, 53% had success with monotherapy, 34% had success with combination therapy, and 13% discontinued therapy. Of 25 patients with melanoma in situ, 20% had success with monotherapy, 56% had success with combination therapy, and 24% discontinued therapy. The drug’s mechanism of action is not entirely understood, but it appears to activate both innate immunity with a cytokine cascade, as well as adaptive immunity with Langerhans cells. "It also causes a direct apoptotic and antineoplastic effect," he said. In his opinion, high-utility niches include any patient seeking minimized scarring and who doesn’t want surgery, electrodesiccation and curettage (ED & C) failure, partially infiltrative or partially superficial BCC, multifocal temporal BCC, and large and/or ill-defined facial SCC in situ. He finds that using imiquimod after ED & C in challenging tumors or in tumors with an infiltrative component increases the cure rate and decreases scarring. "I contend that imiquimod after ED & C generally gives you a better scar than ED & C alone," he said. "I don’t know why, but it does. Brisk reaction can be challenging, and close monitoring is required." Using imiquimod prior to excision "may shrink tumors, leading to a smaller defect, better cosmesis, possible lower recurrence rate, and potential for complete nonsurgical response," he added. He also finds the drug helpful for infiltrative BCCs in cosmetically vulnerable areas and for edge persistence after Mohs surgery. "Part of this is because imiquimod seems to work better on infiltrative basal cell carcinomas than it does on nodular basal cell carcinomas," he explained. "I think that’s because of access of the immune system to the thin threads of tumor. It’s also useful for melanoma in situ, particularly in cosmetically vulnerable areas. With melanoma in situ, melanin is a visible marker that serves as a clinical treatment site monitor. I don’t know of any reports of amelanotic transformation from imiquimod. Scarring is often minimal or absent, and there is tumor margin auto detection. It does have curative potential for melanoma in situ." He emphasized that imiquimod monotherapy in patients with melanoma in situ is difficult, with varied response. "That’s where 5-FU [fluorouracil] in addition to imiquimod is often extremely useful," he said. Dr. Kraffert described imiquimod as "a thinking practitioner’s medication" that requires thought and oversight. "It may provide excellent outcomes when least expected, so it’s important to keep an open mind regarding the clinical utility of this medication with skin cancer," he said. Patients must be able to follow instructions, comply with treatment, return for monitoring and surveillance, and call or return to the clinic when appropriate. "Believe it or not, these limited requirements exclude many potential candidates," he remarked. Patients typically use the drug for 6 weeks, beginning with twice daily dosing, "but it’s variable," he said. "For optimal success treatment must be strong enough for long enough." At the initial consultation Dr. Kraffert educates his patient about the concept of delayed gratification, the reasons why the medication was suggested, and reaffirms that he will be there to oversee treatment. He instructs them on how to use the medication, explaining they need to rub it into the lesion twice a day very well. "A pinhead amount is all that’s needed," he said, only a small portion of the 0.25 g included in each packet. His patients typically get a few to several applications from each packet. He also educates patients about possible side effects from imiquimod, including redness, crusting, oozing, and some tenderness. "Nausea, malaise, pain, and secondary infection are rare," he said. "Patients are advised to call the office with any significant treatment related concerns and are generally offered the option of a same day add-on appointment." At the 2-week follow-up visit he gauges the response as very brisk, brisk, moderate, mild, or none. If the response is very brisk, he halts therapy for 3-7 days, re-initiates treatment once daily for 4 weeks, and schedules a follow-up visit after 2 more weeks of treatment. If the response is brisk, he halts therapy for 1-3 days, and then continues therapy once daily for 4 weeks. If the response is moderate he continues therapy once daily for 4 weeks, and if the response is mild he continues therapy twice daily for 4 weeks. "If there is no response, consider further imiquimod treatment with 2-4-week re-evaluation, or consider application of a small (less than a pea-sized) amount of 5% 5-FU after imiquimod twice daily," Dr. Kraffert said. "Or, you could consider nonimiquimod management of the problem. Sometimes imiquimod just doesn’t work." After the 2-week follow-up, further visits are discretionary, he said, but some patients require closer follow-up, including nonresponders and patients with severe reactions, systemic complaints, and large or challenging tumors. "Scheduling a follow-up visit for 3-6 months is best because the reaction takes a month or 2 to diminish," he said. "Taking photos pretherapy and at each visit thereafter improves surveillance." "There are many approaches to skin cancer," Dr. Kraffert concluded. "Excision or destruction is often the best, but having more options is a plus. Imiquimod doesn’t replace what we have, it just adds to it." Dr. Kraffert said he had no relevant financial conflicts.


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