Treatment of Stage IV Melanoma


Patients with stage IV (metastatic) melanoma have cancer that has spread from its site of origin to lymph nodes as well as to other sites in the body. There is no standard treatment for stage IV melanoma; the medical consensus is that these patients should be considered for clinical trials. There is no highly effective treatment for this stage of melanoma. Therapy may be palliative—intended to reduce pain and discomfort and improve quality of life.

Approved systemic therapies (treatments that affect the entire body, such as chemotherapy, as opposed to local treatment, such as surgery) are only moderately beneficial to patients with stage IV disease. Although there are many choices of therapy, most patients with stage IV melanoma experience cancer progression. Currently available treatments produce a response in approximately 5 percent to 10 percent of patients with stage IV melanoma. The fact that some patients respond, and that some of the responses are long-lasting, is reason for some optimism about the treatment of stage IV melanoma.

The most widely used treatment strategies for stage IV melanoma are:

  • Chemotherapy
  • Biologic agents
  • Combination therapy with chemotherapy and biologic therapy
  • Surgery

Chemotherapy combined with biologic agents offer the promise of higher response rates and long-term durable remissions. It is the focus of most current studies of initial treatment of metastatic melanoma.

The prognosis for stage IV melanoma depends on  number of factors. These include how far the cancer has spread. Metastasis to distant lymph nodes or to the lungs have a better outlook than spread to other sites, such as the brain or liver.

Chemotherapy for Stage IV Melanoma

One of the most commonly used chemotherapy agents for stage IV melanoma is DTIC (dacarbazine). This drug has shown an overall response rate of approximately 15 percent to 20 percent. Trials of a three-drug regimen made up of DTIC, Platinol® (cisplatin), and BCNU (carmustine) have achieved response rates of up to 20 percent. These agents have produced a response for an average duration of 6 to 9 months and have resulted in average survival times of 6 to 11 months. At present, however, no combination treatment has been shown to be more effective than DTIC used alone. A new oral chemotherapy drug, Temodal® (temozolomide), alone or combined with thalidomide, may also be effective in improving survival time and quality of life for patients with metastatic melanoma.

Treatment with Biologic Agents for Stage IV Melanoma

Biologic agents, also called immunotherapy, are treatments that stimulate or restore the ability of the immune system to fight cancer. Several compounds are being studied that boost, direct, or restore normal immune defenses. The most commonly used are alpha-interferon and interleukin-2. These two agents have been the focus of a great deal of melanoma treatment research since the early 1980s. They are believed to work by activating certain cells of the body’s immune system that attack and kill cancer cells.

Overall response rates of approximately 15 percent have been achieved with alpha-interferon. High doses of alpha-interferon appear to be more effective, but are also more toxic, than low doses. Studies combining alpha-interferon with other agents have not shown these combinations to be more effective than alpha-interferon alone.

Interleukin-2 has been found to produce response rates ranging from 8 percent to 22 percent. Many studies have been done on high-dose interleukin-2 for advanced melanoma. These high doses also produce toxic side effects. To receive the treatment, the patient must be hospitalized and closely monitored.

Recently, for the first time a drug demonstrated a survival benefit in advanced melanoma.Patients receiving ipilimumab (Bristol-Myers Squibb) plus a peptide vaccine had a median survival of 10 months, compared with 6.4 months for patients receiving the vaccine alone. Ipilimumab also showed, compared with the peptide vaccine, a near doubling of the rates of survival at 12 months (46% vs 25%) and 24 months (24% vs 14%). Ipilimumab was generally well tolerated, but the study authors noted that the "side effects can be life-threatening and may be treatment limiting." You should discuss whether this treatment is appropriate for you with your oncologist.

Combination Treatment with Biologic Agents and Chemotherapy for Stage IV Melanoma

Some research has focused on combining chemotherapy with immunotherapy for the treatment of advanced melanoma. Combining DTIC and alpha-interferon boosted response rates but did not result in an increase in overall survival. Ongoing studies are comparing the three-agent combination of interferon, interleukin-2, and chemotherapy with chemotherapy alone. At present, no research has shown that biologic agents are superior to chemotherapy in the treatment of advanced melanoma.

Surgical Treatment of Stage IV Melanoma

Since there is no highly effective chemotherapy for advanced melanoma, surgery may be performed as palliative treatment. Surgery can, for example, relieve symptoms of obstruction and bleeding. Some patients with isolated metastases may benefit from complete removal of the growths. This is true if the disease has certain favorable characteristics, such as a long period of time between diagnosis and recurrence. In some cases, surgical treatment can result in survival for up to 10 years.

Not everyone with stage IV melanoma is a good candidate for surgery. Surgery is used only when the tumors are accessible and the patient is healthy enough to survive the procedure. The location of the metastatic growths is also taken into consideration. Certain tumors in the gastrointestinal tract, brain, lung, and distant lymph nodes are often treatable with surgery, whereas those in the liver are usually less amenable to this approach.

Treatment of Brain Metastasis

Brain metastasis accounts for up to 50 percent of reported deaths from melanoma. Standard treatment is whole-brain radiation treatment, which can provide some relief of symptoms. The decision to recommend surgery should be based primarily on whether the entire melanoma can be removed and the status and number of other organs involved with metastatic cancer.

This content was last reviewed August 15, 2010 by Dr. Reshma L. Mahtani.
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