Treatment for Melanoma:

Treatment for melanoma depends on various factors, including:

• The site of the original lesion
• The stage of the cancer
• The patient's age and general health

Treatment options include:

• Surgery to remove the melanoma cancer cells
• Chemotherapy
• Immunotherapy
• Radiation therapy
• Symptom relief (palliative therapy)

Surgery

Surgery is the primary treatment for all stages of melanoma. Some or all of the melanoma is often removed during the first biopsy. If cancerous tissue still remains after such a biopsy, a surgeon will cut away additional tissue from the surrounding area to remove any stray cancer cells.

Surgical management of melanoma that develops in rare sites, such as the vagina, cervix and ovaries, is becoming less aggressive. Studies have shown that wide local excision is equal to radical surgery in many of these cases. Melanoma of the urethra, bladder and ureter usually requires extensive surgery, however.

Mohs micrographic surgery is a technique used to remove very thin layers of skin, one at a time. Each layer is examined immediately under a microscope. When the layers are shown to be cancer-free, the surgery is complete.

The amount of tissue removed depends on the size, depth, and degree of invasion:

• Stage I lesions that are less than 1 mm deep require the smallest surgical cuts, usually about 1 cm off each side and downward from the original lesion.
• For melanomas that are 2 mm or thicker, a margin of 3 cm is important for reducing the risk that the cancer will return.
• Thicker lesions require wider surgical cuts.

Doctors used to remove a large area, regardless of the cancer stage. This potentially disfiguring approach has been abandoned because studies have shown that removing wider margins does not improve survival. Nevertheless, sometimes skin grafts may need to be taken from other body sites to help cover the wound.

Lymph Node Removal. If there is evidence that melanoma has spread to nearby lymph nodes but has not spread beyond them, removing those lymph nodes may reduce the chance of recurrence and help patients live longer.

Surgery for Metastatic Melanoma. In some cases, surgical removal of distant tumors may be possible. This may extend survival, since often in melanoma the cancer spreads first only to a single site, such as the lung or the brain.

Cryosurgery. Cryosurgery freezes skin tissue and destroys it. This procedure is not useful for most melanomas, but it might have some value in specific situations. For example, it may be effective for smaller melanomas in the eye, a location that is difficult to treat with traditional surgery. It may be useful to eliminate cancer cells that remain after standard surgery for lentigo maligna melanomas, an unusual form of melanoma that has a wide surface and is difficult to treat.

Recurrence rates are very high with lentigo maligna after conservative surgery. Although this cancer grows very slowly, lentigo maligna can develop into melanoma. Most of these lesions appear on the face and neck, so extensive surgery can be disfiguring. Patients should carefully discuss with their doctor having surgery to remove all diseased tissue while causing as little cosmetic harm as possible.

Chemotherapy

Chemotherapy is often used to treat melanomas that return or spread. This type of therapy is not intended as a cure, but it can prolong life and improve its quality. Chemotherapy tends to work better than radiotherapy for advanced stage cancers and tumors.

Drugs Used. The following are some of the chemotherapy drugs used to treat melanoma. They may be used alone or in combination under specific situations.

• Methylating agents impair the ability of cancer cells to divide. Dacarbazine (DTIC) and temozolomide (Temodar) are the drugs most often used.
• Nitrosoureas, which include carmustine (BCNU) and lomustine (CCNU) are often used.
• Taxanes, such as docetaxel (Taxotere) and paclitaxel (Taxol), are showing some activity against melanoma.
• Biochemotherapy treatment regimens combine traditional chemotherapy agents, such as cisplatin, vinblastine, dacarbazine, with biologic agents such as interferon alfa or interleukin 2. This combination may be tried for patients with large primary tumors or disease that has spread locally.

Researchers continue to investigate other chemotherapy drugs and combinations of drugs to see which ones work best.

Side Effects. Side effects occur with all chemotherapy drugs. They are more severe with higher doses and increase over the course of treatment.

Common side effects include the following:

• Anemia
• Depression
• Diarrhea
• Fatigue
• Nausea and vomiting
• Temporary hair loss
• Weight loss

Serious short- and long-term complications can also occur, and may vary depending on the specific drugs used. They include the following:

• Abnormal blood clotting (thrombocytopenia)
• Allergic reaction
• Increased chance for infection because the drugs suppress the immune system
• Liver and kidney damage
• Menstrual abnormalities and infertility in women. A natural hormone medication called a gonadotropin-releasing hormone analogue, which puts women in a temporary pre-pubescent state during chemotherapy, may preserve fertility in some women.
• Severe drops in white blood cells (neutropenia). Certain chemotherapy drugs, such as taxanes, pose a higher risk for this side effect. White blood cell count may be improved by adding a drug called granulocyte colony-stimulating factor (either filgrastim or lenograstim).
• Problems in concentration, motor function, and memory, which may be long-term
• Rarely, secondary cancers such as leukemia

Treating Side Effects

Drugs known as serotonin antagonists, especially ondansetron (Zofran), can relieve nausea and vomiting in nearly all patients given moderate drugs, and in most patients who take more powerful drugs.

Erythropoietin stimulates red blood cell production and can help reduce or prevent anemia related to chemotherapy. It is available as epoetin alfa (Epogen, Procrit) and darbepoetin alfa (Aranesp). Aranesp lasts longer in the blood than epoetin alfa, so it requires fewer injections.

Benefits of Chemotherapy. About 20% of cancers shrink in response to one or more of these drugs, but the effects last only 3 - 6 months. If the tumors completely disappear, the cancer may stay in remission much longer, but in virtually all cases it returns.

Chemotherapeutic Regional Perfusion

Chemotherapeutic regional perfusion (also called isolated limb perfusion) is a technique used to give a person very high-dose chemotherapy. It is often used effectively for melanoma that returns or spreads and that occurs on the arm or leg. It does not appear to be useful for preventing cancer spread after a first occurrence of melanoma in one of these locations.

This technique involves the following:

• The blood supply to the limb with melanoma is temporarily interrupted using a tourniquet and then rechanneled through a heart-lung machine.
• Anticancer drugs are added to the blood in up to 10 times the standard doses.
• The blood is then heated to enhance the drug's potency.
• The chemo-infused blood is sent directly to the melanoma site, minimizing the likelihood of drug toxicity.
• Adverse effects occur in less than 1% of cases, and include severe problems in the treated limb (rarely leading to amputation) and drug leakage into the bloodstream. This can severely reduce white blood cells and lead to serious infection.

In addition to its use in the arms and legs, perfusion techniques have also been tested for the pelvis, head, neck, skin of the breast, and even the abdomen.

Immunotherapy

Immunotherapy uses drugs to boost the patient's own immune system. Immunotherapy after surgery may help prevent recurrence in certain people with melanoma. These medicines are usually given along with chemotherapy, other immunotherapies, or both.

Immunotherapy drugs being used include:

• Interferon alpha is FDA-approved immunotherapy for stage IIIB melanoma. Pegylated interferon alfa 2B has shown a positive effect on relapse free survival rate for stage III melanoma. Although interferon drugs have provided some benefit, their use is controversial because of significant toxic side effects.
• Interleukin-2 (Proleukin) is a hormone-like substance that stimulates the growth of cancer-fighting white blood cells. High-dose interleukin-2 has been shown to help patients with melanoma that has spread. The drug can cause significant side effects, including very low blood pressure, heart rhythm abnormalities, severe infections, and shortness of breath. The side effects are manageable, however, and nearly always reversible.

Vaccine Immunotherapy. Vaccine immunotherapy is the use of a specific vaccine to treat an existing cancer. In this case, the vaccine targets one or more proteins that are produced by melanoma cells.

Vaccine immunotherapy requires the body to build up its own defenses. It can take months before benefits occur, but when they do, tumor reduction is more lasting than with chemotherapy. Vaccines also seem to have fewer side effects than interleukin and interferon.

Many therapeutic melanoma vaccines are in the advanced stages of development, but none is approved for use in the United States, because they have not proven to be successful.

Radiation

In general, radiation is used to help relieve pain and discomfort caused by cancer that has spread or recurred. Radiation is not used as often for treating melanoma as it is for other forms of cancer because melanoma cells tend to be more resistant to its effects. It may be useful in the following cases:

• Patients unwilling or unable to have surgery.
• In some patients with tumors less than 3 cm deep, radiation may help slow down cancer spread when combined with a super-heating process using microwaves.
• In some high risk patients with melanoma that has spread to lymph nodes, surgery combined with regional radiation (adjuvant radiotherapy) may reduce the rate of reoccurance.
• Brachytherapy, in which radioactive seeds are implanted close to the tumor, has been used with success for melanoma of the eye.
• Lentigo maligna may sometimes be treated successfully with specific radiation treatments called soft, or Grenz, x-rays.
• Radiotherapy using a gamma knife (very focused gamma radiation) is also effective for cancer that has spread to the brain. In some cases it halts the cancer growth and, in rare situations, even eliminates it.

Palliative Therapy

The goal of palliative therapy is to improve the patient's quality of life and relieve symptoms. It is not a cure. Advanced melanoma that has spread to distant sites often cannot be cured, although surgery to remove tumors that have spread may provide some benefit by easing pain, increasing the general quality of life, and lengthening survival.

Patients should ask their doctors about clinical trials, studies that examine new immunotherapies (vaccines, cytokines), gene therapies, chemotherapy combinations, or other treatments.