Melanoma Review: Background and Treatment

Eva Berrios-Colon, PharmD, MPH, BCPS; Shalonda Williams, PharmD


US Pharmacist 

In This Article


The treatment of melanoma depends upon the stage of disease. The stage of cutaneous melanoma is directly associated with the development of metastatic disease. If the melanoma is diagnosed at an earlier stage, surgical excision is the treatment of choice. For melanomas that have lymphatic involvement, surgical excision may not be enough, and lymph biopsy may be warranted.[3,4]


The surgical excision margin is the most important determinant of outcome in early-stage melanoma. Thin (<1 mm) melanomas require an incision of less than 1 cm. The cure rate for melanomas smaller than 1 mm is as high as 98%.[10] Midsize melanomas (1–2 mm) usually require an incision of 2 cm. Larger melanomas (>4 mm) may have lymphatic involvement and are associated with a high rate of recurrence. These tumors also require a maximum surgical incision margin of 2 cm.

Surgery is usually limited to patients with early-stage disease. Patients with stage III melanoma usually have lymph node involvement or in-transit metastasis. Intransit metastasis is when a tumor develops in the lymph vessel between the primary melanoma and the regional lymph node basin.[11] In-transit metastases occur more than 2 cm from the original site and are more common in individuals with thick, ulcerated lesions. Surgery is also used to manage these distinct melanoma-associated lesions.


Melanoma is one of the most immunogenic solid tumors. Immunotherapy appears to be a viable treatment option, as more traditional cancer treatments do not always yield positive results in cases of melanoma. Complete response rates to immunotherapy vary in patients with melanoma, but generally they are low.

Interferon (IFN) alfa is approved for adjuvant therapy in metastatic melanoma. For patients who have undergone surgical resection for lesions larger than 2 mm, with or without regional lymph node metastases, the only effective adjuvant therapy is IFN.[12] Various trials have evaluated different doses and schedules of IFN therapy for metastatic melanoma. The optimal IFN treatment modality has not been established for the management of metastatic melanoma. Some of the disadvantages of IFN therapy are high cost, unclear long-term benefit, and toxicities (e.g., liver toxicity). IFN is known to cause constitutional symptoms manifesting as fever, chills, myalgia, and fatigue. These symptoms have been treated with acetaminophen, nonsteroidal anti-inflammatory drugs, and meperidine. The most common dosages of IFN alfa therapy are listed in Table 1 .[13,14]

Interleukin-2 (IL-2), a glycoprotein produced by activated lymphocytes, may be immunosuppressive. The role of immunosuppressive properties in melanoma is not fully understood. IL-2 does not have a direct effect on the tumor; rather, it works to regulate immunologic activity. Because of severe multiorgan toxicity associated with IL-2 therapy, treatment with higher doses of IL-2 is reserved for patients with good organ function who are being closely monitored by experienced clinicians. The high-dose regimen of recombinant IL-2 (aldesleukin) used to treat metastatic melanoma is 600,000 IU/kg/dose every 8 hours, for a maximum of 14 doses in a 5-day period, given for two cycles, with a 10- to 14-day rest period between cycles.[11] Common side effects of IL-2 include hypotension, arrhythmias, severe infections, and shortness of breath; these effects are reversible.

Patients with stage IV malignant melanoma require cytotoxic, single- or double-agent, systemic therapy. Single-agent chemotherapy with dacarbazine, temozolomide, or fotemustine should be used in selected patients who are not candidates for treatment with high-dose IL-2. Poor response to chemotherapy or immunotherapy alone has led to the evolution of combination therapy. Biologic therapy has been combined to increase overall activity and, perhaps, response rates.[3]


Ipilimumab (Yervoy) was approved by the FDA in March 2011 to treat advanced or metastatic melanoma.[15] Ipilimumab is a human immunoglobulin G1 monoclonal antibody that exerts its action by blocking cytotoxic T lymphocyte–associated antigen 4, thereby increasing T-cell activation and proliferation. Ipilimumab activates the immune system, causing antitumor action.[11] The National Comprehensive Cancer Network recommended ipilimumab as a category 1 treatment option for metastatic melanoma following a phase III trial that showed an overall survival benefit.[16] The usual dosage of ipilimumab in metastatic melanoma is 3 mg/kg IV every 3 weeks for four doses.


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