Patient information: Melanoma treatment; advanced or metastatic melanoma

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 are 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 (figure 1). 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 metastases are the skin (subcutaneous tissue, (figure 2) 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 advanced 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 medical treatments (chemotherapy or immunotherapy), surgery, or radiation therapy.

Chemotherapy and immunotherapy treatments may be given alone or in combination. 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, often several months or more, depending upon how you respond.

Chemotherapy — Chemotherapy refers to the use of medicines to stop or slow the growth of cancer cells. These drugs work by interfering with the ability of rapidly growing cells (like cancer cells) 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.

Dacarbazine (DTIC) — DTIC is considered to be the most active chemotherapy drug for metastatic melanoma. Although tumor shrinkage is seen in 8 to 20 percent of treated patients, most people respond only partially (that is, the tumor does not disappear entirely) and the benefit lasts only four to six months.

DTIC is given into a vein over one hour for five days every three weeks. It is generally well tolerated; nausea and vomiting are the most common side effects. Anti-nausea medications are given with DTIC to reduce discomfort.

Temozolomide — Temozolomide is medication that is taken by mouth as a capsule. It is usually taken for five days every four weeks. It acts similar to DTIC. Unlike some other treatments, temozolomide is able to penetrate into the brain and other parts of the nervous system. For this reason, it is often used to treat people with metastases to the brain. Further study is needed to determine the best dose to temporarily slow or stop the growth of metastases.

Immunotherapy — In contrast to chemotherapy, immunotherapy works with your immune system to stop or slow the growth of cancer cells. Because immunotherapy works differently than chemotherapy, it has different side effects. Immunotherapy has less effect on the bone marrow, hair, and lining of the GI tract. However, many immunotherapy agents (eg, interferon alpha or IFNa) cause symptoms similar to the flu, such as low-grade fever, chills, muscle and/or joint aches, and headache.

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 [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.

Interferon alpha — IFNa is an immunotherapy agent is often used after surgery in people with advanced or metastatic melanoma.

Other treatments — Other experimental treatments are being studied for advanced metastatic melanoma. These include monoclonal antibodies (specially formed proteins designed to attack cancer cells), melanoma vaccines, gene therapies, cellular therapies (adoptive immunotherapy) as well as various targeted (those that directly attack the growth of the melanoma) and anti-angiogenic agents (those that shrink the blood vessels of the cancer).

Currently, none of these treatments has been shown to improve survival more than IL-2 or chemotherapy.

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

Modest progress has been made in the treatment of metastatic melanoma over the past decade. With the advent of high dose interleukin-2 (IL-2), it may be possible for a small number of people to be cured of their disease (graph 1).

Despite this, the average survival in people treated for metastatic disease may be as short as nine months (graph 2). Because IL-2 treatment can have severe side effects, the risk of undergoing treatment with high dose IL-2 outweighs the small potential benefit for some people (see 'Interleukin-2 (IL-2)' above.

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/clinical_trials/learning/

       www.cancer.gov/clinical_trials/

       http://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. Because no two people are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.

This discussion will be updated as needed every four months on our web site (www.uptodate.com/patients). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.

Some of the most pertinent include:

Patient Level Information:
Patient information: Melanoma treatment; localized melanoma

Professional Level Information:
Adjuvant interferon alfa for intermediate- and high-risk melanoma
American Joint Commission on Cancer staging system and prognostic factors in cutaneous melanoma
Approach to the patient with macular skin lesions
Cutaneous melanoma: Management of in transit metastases
Cutaneous melanoma: Management of local recurrence
Cytotoxic chemotherapy and biochemotherapy for metastatic melanoma
Evaluation and treatment of regional lymph nodes in melanoma
Experimental immunotherapy for melanoma
Imaging studies in melanoma
Inherited susceptibility to melanoma
Initial surgical management of melanoma of the skin and unusual sites
Interleukin-2 and interferon alfa in the treatment of metastatic melanoma
Management of brain metastases in 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 follow-up guidelines for melanoma
Surgical management of metastatic melanoma
Uveal and conjunctival melanoma
Hospice: Philosophy of care and appropriate utilization

A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable.

• 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

      (http://cancer.about.com/forum)

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