Types of Therapy for Melanoma

Surgery: Surgery is the mainstay of therapy for early stage melanoma and for resection of an isolated metastatic melanoma site. Skin biopsy techniques and sentinel lymph node biopsy have been discussed, in general terms, previously and are the most common types of surgery used in melanoma; however, many other types of surgery are employed when appropriate. The initial biopsy may be performed by a dermatologist or a dermatologic surgeon. Surgery may be performed by a surgical oncologist, a plastic surgeon, a head and neck surgeon, or a combination of these specialists.  Types of surgery are:
 

• Simple Excision:  thin melanomas are removed along with a small amount of non-cancerous skin at the edges.
• Mohs Surgery:  a small section of apparently normal skin beyond the visible melanoma is removed and looked at under a microscope.  If abnormal cells are identified another small section is removed and this process continues until the cells removed no longer look abnormal.
• Wide Local Excision:  this excision is used to decease the change of local recurrence.  A wide excision, usually 1-2 cm, is made around the original melanoma site and the tissue is sent to the pathologist for evaluation.
• Sentinel Lymph Node Biopsy:  during a sentinel lymph node biopsy, a radioactive tracer and a dye are injected into the site of the primary melanoma. These agents are then traced to the “draining” lymph node basin. A small incision is made into the area where these two agents traveled and the lymph nodes involved are removed. They are then examined under a microscope to determine if there are any melanoma cells detected. In no melanoma cells are found, then no further surgical intervention is performed. If this lymph node does contain melanoma cells, then a second surgery to remove additional lymph nodes will be performed. These additional lymph nodes are also evaluated by a pathologist to determine if they contain any melanoma cells. This information is important in determining the stage of a person’s melanoma.  (moved from another area)

Immunotherapy:  Immunotherapy is a type of systemic therapy useful in the treatment of melanoma at high risk for recurrence and for metastatic disease. The goal of immunotherapy is to treat the whole body. Immunotherapy is given in an attempt to activate a person’s own immune system so that it will destroy any melanoma cells within the body. Immunotheapy is prescribed and administered by a medical oncologist.

Immunotherapy can be given in a variety of ways. The most well known way in melanoma is by using biologic agents that stimulate the immune system. Other mechanisms of stimulating the immune system are currently under investigation through clinical trials and include vaccine therapy, stem cell manipulation, among others.

Commonly prescribed immune stimulants include the biologic agents, the interferons and interleukins. These agents are administered in much higher doses than are usually present in the body. Common side effects include flu-like symptoms.

Interferon alpha 2-b is currently FDA-approved for the treatment of high risk Stage II and Stage III melanoma. Its approved dosing schedule is one month of high dose intravenous therapy followed by 11 months of sub-cutaneous injections. There are many side effects associated with Interferon therapy. On-going clinical trials are investigating its use in earlier stage melanoma as well as alternate dosing schedules.

Interleukin-2 is currently FDA-approved for the treatment of Stage IV melanoma. Its approved dosing schedule is 2 cycles of high dose intravenous therapy, requiring hospitalization, administered in specialized medical centers. There are many acute toxicities associated with Interleukin therapy and extremely close monitoring is essential for safe administration.

Other immune stimulating agents that have been used in the treatment of melanoma include Bacillus Calmette-Guerin (BCG), Corynebacterium parvum, and the immunomodulator levamisole.

Chemotherapy:  Chemotherapy is a type of therapy in which a medication is given to treat melanoma. The goal of chemotherapy is to destroy melanoma cells throughout the body. Chemotherapy is prescribed and administered by a medical oncologist, a physician specially trained in oncology. The medical oncology team usually consists of physicians and specially trained nurses.

Dacarbazine (DTIC) is the only FDA-approved chemotherapy agent for the treatment of Stage IV melanoma. It is administered as an intravenous infusion. Temozolomide is an oral chemotherapy agent which is considered an oral form of dacarbazine. This medication is not FDA-approved for the treatment of melanoma, but is often used in that setting with similar efficacy to its stage IV counterpart. Other chemotherapy agents are commonly used for the treatment of metastatic melanoma, including the taxanes (i.e. docetaxel, paclitaxel) and platimum agents (i.e. cisplatin, carboplatin). Many other chemotherapy agents are being evaluated for their use in the treatment of Stage IV melanoma as both single agents and in combination with other chemotherapy, targeted, and immunotherapy agents.

About half of all melanomas occur in the extremities, and about 10% of patients with those lesions develop a recurrence as in-transit disease. Isolated limb perfusion (ILP) was developed for locoregional delivery of chemotherapeutic agents and potential limb salvage.

Another type of chemotherapeutic agent which is being investigated through clinical trials for the treatment of melanoma are targeted agents. Targeted agents are different than traditional chemotherapy agents in that they do not cause global cell death. Instead they are able to specifically target a certain protein in the cell or on its surface that has been found to be altered in melanoma. Many of these agents are currently being investigated through clinical trials.

Radiation Therapy:  In the adjuvant setting (resected melanoma), radiation therapy is used to prevent a local recurrence of the melanoma. This therapy is often used when clear margins are not obtainable, when there are matted lymph nodes or extracapsular extension in the affected lymph nodes. Radiation therapy can be delivered on a variety of schedules. Therapy is planned by a radiation oncologist, a physician specially trained in radiation therapy. The radiation oncology team is comprised of physicians, physicists, nurses, and radiation technicians specially trained in radiation oncology.

In the metastatic setting, radiation therapy is often used to treat isolated melanoma metastases or to relieve symptoms caused by a specific melanoma lesion. Radiation therapy is often used to treat brain metastases resulting from melanoma as well as metastatic bone lesions.

Another specialized type of radiation therapy is stereotactic radiosurgery. This type of radiation
delivers a very high dose of radiation therapy to a specific area. Gamma Knife and Cyber Knife are two types of stereotactic radiosurgery.

Regional Perfusion (Isolated Limp Perfusion): Regional perfusion is a procedure used to treat one limb of the body that has multiple areas of metastasis from melanoma that cannot be removed by surgery alone.  In this procedure, the blood supply to that limb is temporarily isolated, and a chemotherapy agent is heated and infused into that limb.  Melphalan has become the gold standard for ILP.

Treatments Under Investigation:

• Targeted Therapy: finding medicines that will specifically interfere with abnormal melanoma cell signals to stop melanoma cell growth
• Cancer Vaccines: treatment that aims to help recruit the body’s own immune system to target and kill cancer cells
• Other Immune Stimulants: clinical trials are using:  Anti-CTLA-4 antibodies, Anti-PD-1 antibody, Anti-CD137 antibody and Anti-CD40 antibody
• Cellular Immune Therapy:  the body’s own immune cells can be genetically and otherwise altered to make them better able to recognize and kill tumor cells

Clinical Trials: Clinical Trials are research studies to test promising new or experimental cancer treatments; new ways to detect melanoma; or new ways to monitor melanoma.  Clinical trials are often thought of as the standard of care for Stage IV.  The trials offer melanoma patients the opportunity to receive care that is not yet the standard.  These trials undergo multiple levels of scrutiny before they are offered to the patient.  The participants can benefit directly from the trial and/or the information learned can help patients with melanoma in the future.

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