Background: Locoregional advanced melanoma poses a complex clinical challenge that requires a multidisciplinary, patient-centered approach. Numerous agents have been studied for their suitability as intralesional therapy in the past decades, but few have successfully completed phase 3 clinical trial testing.
Methods: The relevant medical literature was searched for articles regarding use of intralesional therapies in metastatic melanoma. Therapies with data from phase 2 or higher studies were selected for review. This review also summarizes the mechanisms of action, adverse-event profiles, and clinical data for these agents. Results: Intralesional therapies demonstrate promising effects in select patients with advanced melanoma. The optimal approach should be individually tailored and consist of a combination of intralesional therapies, regional perfusions, systemic immunotherapies, targeted therapies, and surgery, if necessary.

Conclusions: Due to its relatively good local response rates and tolerable adverse-event profile, intralesional therapy may be a treatment option for select patients with unresectable, locally advanced or metastatic melanoma.

Intralesional therapy is a possible treatment option for patients with metastatic melanoma due to its good local response and tolerable adverse-event profile.

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Melanoma is accountable for most deaths related to skin cancer.1 In 2016, an estimated 76,380 new cases of melanoma will be diagnosed and approximately 10,130 people will die from the disease in the United States alone.1 Although cure rates are high if the disease is discovered when confined to its primary location, metastasis frequently occurs.1 A unique clinical challenge posed by locoregional metastasis, also known as intralymphatic metastasis, occurs when metastasis develops between the primary melanoma and the draining lymph-node basin. This type of metastasis, which occurs in 5% to 10% of patients with melanoma, has traditionally been classified into 2 categories: satellite metastases (located < 2 cm from the primary tumor) and in-transit metastasis (located ≥ 2 cm from the primary tumor).2,3

Surgical resection is the standard of care for patients whose disease is limited enough to be rendered with no evidence of disease. If disease is confined to the limb, then unresectable disease can be amenable to locoregional treatment. For example, regional perfusion therapies, such as isolated limb infusion or hyperthermic-isolated limb perfusion, have demonstrated objective response rates (ORRs) of 50% to 90%.4,5 These treatments can be repeated multiple times, depending on response and rate of toxicity. The disadvantages of limb infusion and perfusion include associated regional toxicity, morbidity from a surgical procedure, and applicability to disease confined to the extremities alone (eg, not applicable to in-transit metastasis on the trunk). Although radiotherapy is frequently used to treat microscopic disease in an adjuvant setting, macroscopic melanoma is difficult to treat with radiotherapy and has been used to treat individual lesions or localized clusters with anecdotal success; however, wide-field irradiation is associated with morbidity and is not a preferred first-line modality.6,7