Melanoma treatment; advanced or metastatic melanoma

Melanoma treatment; advanced or metastatic melanoma

Author
Jeffrey A Sosman, MD
Section Editor
Michael B Atkins, MD
Deputy Editor
Michael E Ross, MD

Disclosures

MELANOMA OVERVIEW — Melanoma is a serious form of skin cancer that develops in the skin cells that make our skin color (melanocytes). Melanoma is the sixth most common cancer in the United States, and the number of melanoma cases diagnosed annually is increasing faster than for any other cancer.

After melanoma is diagnosed, the next step is to determine the cancer’s stage, which describes the size, spread, and aggressiveness of the cancer. Staging is also important to determine the most appropriate treatment. Melanoma often starts as a single tumor or lesion. Cancer cells can spread to near-by lymph nodes and distant sites throughout the body. Once it spreads to distant locations, it is called advanced or metastatic melanoma.

This article discusses the treatment of stage IV (advanced or metastatic) melanoma. The diagnosis and treatment of localized melanoma is discussed separately. (See “Patient information: Melanoma treatment; localized melanoma”.)

MELANOMA STAGING — For people with stage IV disease, the melanoma has spread beyond the local area into other areas or organs. The most common sites of such spread (metastases) are under the skin (subcutaneous tissue) (figure 1) and other soft tissues (including lymph nodes), the lungs, liver, brain, and bone. However, metastasis to organs such as the adrenal glands, spleen, and gastrointestinal tract can also occur.

MELANOMA TREATMENT — Treatment of metastatic melanoma focuses on:

Shrinking or getting rid of metastases
Preventing the disease from spreading
Keeping you comfortable
In most cases, it is not possible to completely eliminate or cure the cancer. Depending upon where and how big the metastases are, treatment may involve drug treatments, surgery, or radiation therapy.

Drug treatments — There are three main categories of drug treatments:

Immunotherapy – drugs that work with your immune system to stop or slow the growth of cancer cells
Targeted therapy- drugs that inhibit specific enzymes or molecules important to the cancer cells
Chemotherapy – drugs that stop or slow the growth of cancer cells by interfering with their ability to divide or reproduce themselves
These drug treatments may be given alone, but combination therapy is being studied to see if it is beneficial. Most of these treatments must be given into a vein (intravenously) or injected under the skin, although a few can be given in pill form. Each medication is given over a period of time, sometimes up to several months, depending upon how you respond.

Immunotherapy — Because immunotherapy works differently than chemotherapy, it has different side effects.

Interleukin-2 (IL-2) — IL-2 is a form of immunotherapy that has been found to help some people with metastatic melanoma when given in high doses. In some people treated with high dose IL-2, the benefit can be long lasting for even 5 to 10 or more years [1-3].

However, high dose IL-2 can cause serious and toxic side effects, and it is generally reserved for people who are otherwise healthy (with good heart and lung function).

IL-2 is usually given into a vein three times per day for five days twice per month. Treatment is usually completed while you are in the hospital.

Potential side effects of IL-2 — Potential side effects of high dose IL-2 include low blood pressure, irregular heart rhythms, accumulation of fluid in the lungs, fever, and rarely death.
Ipilimumab — Ipilimumab is a drug that stimulates the body’s immune system to react against the melanoma. This is given once every three weeks for a total of four doses. Treatment with ipilimumab may decrease the extent of your melanoma and help you live longer. But ipilimumab can also cause the body to develop an immune reaction against its own tissues. This can result in a wide range of side effects that may be severe or life threatening. The most important of these include colitis (causing diarrhea, bleeding, or more serious complications), hepatitis, rash or inflammation of the skin, and inflammation of endocrine organs (pituitary, thyroid, or adrenal). If this occurs, you might have to stop the ipilimumab and receive additional treatment for the complications.

If you take this drug, it is important to tell your doctor about any side effects you experience, even mild ones. This will help avoid the more serious complications.

Targeted therapy — About one-half of melanomas contain a specific mutation in one gene (BRAF) that tells the cell how to make a particular protein, which in turn drives the growth of cancer cells. The melanoma actually becomes addicted to the actions of this protein (oncogene addiction). A specific drug has been developed (vemurafenib) that blocks this protein. This drug causes tumors with that mutation to regress and prolongs the time to disease progression and the overall survival of patients with BRAF mutant tumors compared to chemotherapy. To date, only a few patients have experienced complete tumor regression, and persistent regression of tumor off treatment (“cure”) has not been observed. The most significant common side effect is the development of other (non-melanoma) skin cancers, which can be managed with routine skin cancer care and do not require interruption of vemurafenib therapy.

Chemotherapy — Chemotherapy refers to the use of medicines such as dacarbazine or temozolomide to stop or slow the growth of cancer cells by interfering with their ability to divide or reproduce themselves. Because most of an adult’s normal cells are not actively growing, they are not affected by chemotherapy, with the exception of bone marrow (where the blood cells are produced), the hair, and the lining of the gastrointestinal (GI) tract. Effects of chemotherapy on these and other normal tissues result in side effects during treatment.

With the availability of ipilimumab and vemurafenib, chemotherapy is generally not used as the initial treatment for advanced disease.

Surgery — Surgery may be recommended if melanoma has spread to one or a very limited number of sites. Surgery may prolong survival or relieve symptoms caused by the melanoma. However, surgery is not a cure because metastatic melanoma usually spreads to many different places throughout the body. Surgery can also help to relieve pain caused by a metastatic tumor, such as in the lung or brain.

Whole brain radiation therapy — In some people with melanoma that has spread to the brain, surgery can prolong survival, especially if the disease outside of the brain is controlled. A course of “whole brain” radiation therapy or stereotactic radiation therapy (see below) to the tumor area is generally recommended after surgery to destroy any cancer cells that may remain in the brain.

Stereotactic radiosurgery — If the metastatic tumor(s) is located in areas of the brain that cannot be reached by surgery, or if tumors are multiple and small, a procedure called stereotactic radiosurgery may be helpful in slowing or stopping the tumor growth. Radiosurgery does not involve surgery, but instead uses precisely targeted radiation to destroy cancer cells. Stereotactic radiosurgery may be followed by a course of whole brain radiation therapy.

END OF LIFE CARE — In some people with metastatic melanoma, the disease cannot be cured. Deciding when to stop treating the melanoma can be difficult, and this decision should involve the patient, family, friends, and the healthcare team.

Ending treatment does not mean ending care for the patient. Hospice care is frequently recommended when a person is unlikely to live longer than six months. Hospice care involves treatment of all aspects of a patient and family’s needs, including the physical (eg, pain relief), psychological, social, and spiritual aspects of suffering. This care may be given at home or in a nursing home or hospice facility, and usually involves multiple people, including a physician, registered nurse, nursing aide, a chaplain or religious leader, a social worker, and volunteers.

These providers work together to meet the patient and family’s needs and significantly reduce their suffering. For more information about hospice, see www.hospicenet.org. (See “Hospice: Philosophy of care and appropriate utilization”.)

MELANOMA SURVIVAL — Significant progress has been made in the treatment of metastatic melanoma over the past decade. Two drugs that stimulate the immune system, high dose interleukin-2 (IL-2) and ipilimumab, and the targeted drug vemurafenib are more effective for controlling metastatic melanoma and allowing some people to live longer. However, both forms of immunotherapy (IL-2 and ipilimumab) can be associated with severe side effects, and the duration of benefits with ipilimumab and vemurafenib is not certain. Only in the past few years, ipiliimumab and vemurafenib have been shown to improve overall survival of melanoma patients. This may be surprising, but it is exciting to finally achieve this progress towards making lives of melanoma patients better.

In deciding what treatment is right for you, you and your family must consider the risks and benefits of each option according to your values and preferences.

CLINICAL TRIALS — Progress in treating cancer requires that better treatments be identified through clinical trials, which are conducted all over the world. A clinical trial is a carefully controlled way to study the effectiveness of new treatments or new combinations of known therapies. Ask for more information about clinical trials, or read about clinical trials at:

www.cancer.gov/clinicaltrials/learning/

www.cancer.gov/clinicaltrials/

file://clinicaltrials.gov/

WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem.

 

Related topics for patients, as well as selected articles written for healthcare professionals, are also available. Some of the most relevant are listed below.

Patient Level Information:

Patient information: Melanoma treatment; localized melanoma

Professional Level Information:

Adjuvant interferon alfa for intermediate- and high-risk melanoma
Approach to the patient with macular skin lesions
Cutaneous melanoma: Management of in transit metastases
Cutaneous melanoma: Management of local recurrence
Evaluation and treatment of regional lymph nodes in melanoma
Imaging studies in melanoma
Inherited susceptibility to melanoma
Initial surgical management of melanoma of the skin and unusual sites
Management of brain metastases in melanoma
Ocular melanoma
Pathologic characteristics of melanoma
Primary prevention of melanoma
Risk factors for the development of melanoma
Role of radiation therapy in the management of melanoma
Screening and early detection of melanoma
Staging work-up and surveillance after treatment of melanoma
Surgical management of metastatic melanoma
Hospice: Philosophy of care and appropriate utilization
Cytotoxic chemotherapy for metastatic melanoma
Immunotherapy for advanced melanoma
Molecularly targeted therapy for metastatic melanoma
Ipilimumab (anti-CTLA-4) immunotherapy in advanced melanoma

The following organizations also provide reliable health information.

National Cancer Institute
1-800-4-CANCER
(www.cancer.gov)

The American Society of Clinical Oncology
(www.cancer.net/portal/site/patient)

National Comprehensive Cancer Network
(www.nccn.com)

American Cancer Society
1-800-ACS-2345
(www.cancer.org)

National Library of Medicine
(www.nlm.nih.gov/medlineplus/healthtopics.html)

The Melanoma Center, University of Pittsburgh Cancer Institute
(www.melanomacenter.org)

Melanoma Research Foundation
(www.melanoma.org)

Patient support — There are a number of online forums where patients can find information and support from other people with similar conditions:

About.com Cancer Forum
(file://cancer.about.com/forum)

REFERENCES
Atkins MB, Lotze MT, Dutcher JP, et al. High-dose recombinant interleukin 2 therapy for patients with metastatic melanoma: analysis of 270 patients treated between 1985 and 1993. J Clin Oncol 1999; 17:2105.
Atkins MB, Kunkel L, Sznol M, Rosenberg SA. High-dose recombinant interleukin-2 therapy in patients with metastatic melanoma: long-term survival update. Cancer J Sci Am 2000; 6 Suppl 1:S11.
Tarhini AA, Kirkwood JM, Gooding WE, et al. Durable complete responses with high-dose bolus interleukin-2 in patients with metastatic melanoma who have experienced progression after biochemotherapy. J Clin Oncol 2007; 25:3802.
Elwood JM, Jopson J. Melanoma and sun exposure: an overview of published studies. Int J Cancer 1997; 73:198.