Treatment for Melanoma

The standard treatment for primary melanoma is surgical removal (resection). During this procedure, the tumor and an area of surrounding healthy tissue (called margins) is removed. The size of these margins depends on the depth of the tumor. Melanoma that remains confined to the skin is almost 100 percent curable.

Adjuvant Therapies

Melanoma that cannot be removed surgically and/or has spread to lymph nodes or to distant sites requires additional treatment. Adjuvant therapy may include immunotherapy using interferon alpha 2b or interleukin-2. These are immune-stimulating chemicals that helps the body "fight" the cancer.

Some studies show that immunotherapy can prolong life. But the medications are difficult to tolerate—virtually all patients experience flu-like symptoms that can be quite severe. Treatment-related deaths have been reported as well. In experiments with lower doses, patients tolerate the medication better and live a little longer.

Melanoma and Chemotherapy

Various chemotherapy regimens are used to treat metastatic disease, although the results are typically disappointing. Chemotherapy is sometimes combined with immunotherapy. Radiation therapy can relieve some of the pain caused by complications associated with metastatic tumor by reducing the size of a tumor located in the brain, the bones, the skin, or spinal cord.

Metastatic Melanoma Treatment

In March 2011, the U.S. Food and Drug Administration (FDA) approved ipilimumab (Yervoy) to treat metastatic melanoma. This drug, which is a monoclonal antibody, may help the body's immune system to recognize, target, and destroy melanoma cells. In an international study, ipilimumab improved survival in patients with late-stage disease. Side effects include diarrhea, fatigue, rash, and intestinal inflammation. This medication increased the risk for severe autoimmune reactions and its approval includes a strategy (Risk Evaluation and Mitigation Strategy) to inform doctors of these serious risks.

In August 2011, vemurafenib (Zelboraf) was approved to treat a certain type of melanoma that cannot be treated surgically and/or that has spread (metastasized). This drug may be used for late-stage melanoma that contains a certain genetic mutation called BRAF V600E. Also included in this approval is a diagnostic test to identify the specific mutation. Side effects include joint pain, rash and sun sensitivity, hair loss, fatigue and nausea.

Cobimetinib (Cotellic) was approved for use in combination with vemurafenib in November 2015. This medication can help prevent or slow cancer cell growth. Side effects include diarrhea, fever, nausea and vomiting, and sun sensitivity. Severe effects include heart muscle damage (cardiomyopathy), muscle damage, new skin cancers, retinal detachment, and others. Cotellic is not used in women who are pregnant because it can harm developing fetuses.

The FDA approved two new drugs to treat metastatic melanoma and melanoma that cannot be removed surgically in May 2013. These drugs—dabrafenib (Tafinlar) and trametinib (Mekinist)—are approved to treat melanoma that contains the genetic mutations BRAF V600E (Tafinlar) and BRAF V600E or V600K (Mekinist). Initially approved as single agents, they were approved for combination therapy in January 2014.

Side effects may be serious and life threatening (e.g., cutaneous squamous cell carcinoma, kidney failure, heart failure, extremely low blood pressure, others). Common side effects of Tafinlar include thickening of the skin, headache, fever, joint pain, and non-cancerous skin tumors. Common side effects of Mekinist include rash, diarrhea, swelling, and skin breakouts. These medications also can cause infertility in men and women, and fetal harm in women who are pregnant.

Pembrolizumab (Keytruda) was approved by the FDA in September 2014 to treat advanced melanoma that cannot be treated surgically and is no longer responding to other treatments. This medication is the first drug that blocks the cellular pathway known as PD-1, which prevents the immune system from attacking melanoma cells in the body. It is used following treatment with ipilimumab or—in patients with BRAF V600 gene mutation—after treatment with ipilimumab and a BRAF inhibitor.

Common side effects include: fatigue, cough, nausea, rash, loss of appetite, and others. Rarely, Keytruda can cause severe immune system side effects that affect healthy organs (e.g., lungs, colon, liver).

Nivolumab (Opdivo) was approved in December 2014 to treat melanoma that cannot be removed surgically or melanoma that has spread. Like pembrolizumab, this medication inhibits the PD-1 pathway and is used following ipilimumab and a BRAF inhibitor in patients with BRAF V600 mutation. Side effects include rash, itching, cough, respiratory infection, and swelling. Serious side effects, such as organ damage, also may occur.

The first oncolytic virus therapy for treatment of melanoma of the skin and lymph nodes that cannot be completely removed surgically was approved by the FDA in October 2015. Talimogene laherparepvec (Imlygic) is a genetically modified material that is administered as a series of injections directly into melanoma lesions, where it replicates inside cancer cells and caused them to rupture and die. A second injection is administered 3 weeks after the initial dose, followed by injections every 2 weeks for at least 6 months. Therapy is discontinued when another type of treatment is necessary, or when no lesions remain.

At this time, Imlygic has not been shown to improve overall survival rates or to effectively treat melanoma that has spread to internal organs—brain, liver, lungs, etc. Common side effects include fatigue, fever and chills, nausea, and pain at the site of the injections.

Melanoma Vaccine

A major development in treatment is the melanoma vaccine. The vaccine prompts the immune system to recognize and kill the remaining tumor cells before they reproduce and grow. The melanoma vaccine has an overall response rate of 10 to 20 percent. Attempts to increase the immune-stimulating effects of the vaccine are ongoing.

Publication Review By: Stanley J. Swierzewski, III, M.D.

Published: 14 Aug 1999

Last Modified: 10 Nov 2015