Regression of Internal Melanoma Metastases Following Application of Topical Imiquimod to Overlying Skin

March 2011 | Volume 10 | Issue 3 | Case Report | 302 | Copyright © 2011

Anne K. Miller BS, Reginald Dusing MD, Aaron Meggison MD, Daniel Aires MD

University of Kansas School of Medicine, Departments of Dermatology and Radiology, Kansas City, KS

Abstract

The prognosis for metastatic melanoma is grim, and treatment options are limited. Imiquimod is a topically applied immunemodulatorthat has been used to treat superficial cutaneous melanoma, but has not been reported to treat metastatic melanoma. We report a patient whose liver and iliac fossa melanoma metastases regressed after topical application of imiquimod cream to overlying skin. This supports further investigation of the potential use of imiquimod for metastatic melanoma.

J Drugs Dermatol. 2011;10(3):302-305.

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INTRODUCTION

Imiquimod was approved by the U.S. Food and Drug Administration (FDA) in 1997. The 5% formulation is known under the trade names of Aldara and Beselna. A 3.75% formulation is now available under the trade name Zyclara. Aldara and Zyclara are manufactured by Graceway Pharmaceuticals; Beselna is manufactured by Mochida. Imiquimod binds cell surface toll-like receptors 7 and 8, and induces immune responses. Cells activated by imiquimod secrete cytokines including interferon-alpha, tumor necrosis factoralpha and interleukins 6 and 12.1 These cytokines activate Langerhans cells and initiate both innate and acquired immune responses.2–3 Imiquimod cream is widely used to treat actinic keratoses, superficial basal cell carcinomas, warts and superficial melanomas.4 It is applied topically to the skin 2–5 times per week, depending on the type of lesion and the patient’s response. Duration of imiquimod treatment typically ranges from 6–16 weeks.4 We report on a case of apparent regression of metastatic melanoma with the use of superficial imiquimod.

CASE REPORT

A 55-year-old male with a history of coronary artery disease and hyperlipidemia presented with an upper gastrointestinal bleed, melena and anemia requiring transfusion. In March 2008, an EGD showed a gastric mass originally thought to be poorly differentiated adenocarcinoma; this was treated with a gastrectomy one month later. Surgical pathology results showed gastric melanoma. A primary 0.16 mm melanoma was subsequently found on the patient’s right arm, and treated with wide local excision. PET and CT scans in May 2008 showed a metastatic mass in the right iliac fossa adjacent to the iliacus muscle. At this point, a watchful waiting approach with no systemic chemotherapy was adopted.

The patient had been prescribed imiquimod cream to treat a basal cell carcinoma on the left lower eyelid. On his own, the patient decided in June 2008 to start applying imiquimod cream three times per week to his abdominal skin overlying the melanoma metastasis in his lower right quadrant. A second PET scan in August 2008 showed increased uptake in the right iliac fossa lesion as well as new metastatic lesions in the liver and right supraclavicular area. Due to disease progression, the decision was made to pursue a course of IL-2. He stopped the imiquimod to prepare for this, after having used it for three months. The patient was admitted for 14 doses of IL-2 in September 2008. After dose 13 the patient developed IL-2 associated myocarditis, so treatment was discontinued. CT scan in October 2008 showed slight increases in the hepatic metastases and no growth of the iliac fossa metastasis (Figures 1 and 2). It was determined the patient could not tolerate another cycle of IL-2. Both the patient and the oncologists agreed to take a watchful waiting approach because the patient was asymptomatic at that time.

In vitro testing of cosmetic formulations with antioxidants is complex and very often the results achieved in these studies cannot be confirmed in vivo studies. Furthermore, many clinical studies evaluating the efficacy of topical antioxidants are based on the assessment of the prevention of UV-induced erythema and sunburn cell formation.13 However, currently there is no standardized method to evaluate the complex effects of topical formulations combining different antioxidant ingredients.

After August 2009 he continued imiquimod as monotherapy to a larger area, including both the anterior pelvis and the right upper quadrant. Surprisingly, his metastatic lesions regressed, and one completely disappeared. It is possible that application of imiquimod to a larger area could have had an effect on the metastatic lesions.

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