Melanoma Skin Cancer

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Treating Skin Cancer - Melanoma TOPICS

Targeted therapy for melanoma skin cancer

As doctors have found some of the gene changes that make melanoma cells different from normal cells, they have begun to develop drugs that attack these changes. These targeted drugs work differently from standard chemotherapy drugs, which basically attack any quickly dividing cells. Sometimes, targeted drugs work when chemotherapy doesn’t. They can also have less severe side effects. Doctors are still learning the best way to use these drugs to treat melanoma.

Drugs that target cells with changes in the BRAF gene

About half of all melanomas have changes (mutations) in the BRAF gene. These changes cause the gene to make an altered BRAF protein that signals the melanoma cells to grow and divide quickly. Drugs that target this and related proteins are now available.

If you have advanced melanoma, a biopsy sample of it might be tested to see if it contains a BRAF mutation. Drugs that target the BRAF protein (or the MEK proteins) are not likely to work in patients whose melanomas have a normal BRAF gene.

BRAF inhibitors

These drugs attack the BRAF protein directly.

Vemurafenib (Zelboraf): This drug causes tumors to shrink in about half of the people whose metastatic melanoma has a BRAF gene change. It also prolongs the time before the tumors start growing again and helps some patients live longer, although the melanoma typically starts growing again eventually.

This drug is taken as a pill, twice a day. The most common side effects are joint pain, fatigue, hair loss, rash, itching, sensitivity to the sun, and nausea. Less common but serious side effects can occur, such as heart rhythm problems, liver problems, severe allergic reactions, and severe skin or eye problems.

Some people treated with this drug develop new skin cancers called squamous cell carcinomas. These cancers are usually less serious than the melanoma they already have and can be treated by removing them. Still, your doctor will want to check your skin often during treatment and for several months afterward. You should also let your doctor know right away if you notice any new growths or abnormal areas on your skin.

Dabrafenib (Tafinlar): This drug seems to work about as well as vemurafenib in terms of shrinking melanoma tumors when it is used by itself. It is taken as a capsule, twice a day.

Common side effects include thickening of the skin (hyperkeratosis), headache, fever, joint pain, non-cancerous skin tumors, hair loss, and hand-foot syndrome (redness, pain, and irritation of the hands and feet). Although it also can cause squamous cell carcinomas of the skin, these may happen less often than with vemurafenib. Some other more serious side effects that can occur with dabrafenib include severe fevers, dehydration, kidney failure, eye problems, and increased blood sugar levels.

MEK inhibitors

The MEK gene is in the same signaling pathway inside cells as the BRAF gene, so drugs that block MEK proteins can also help treat melanomas with BRAF gene changes.

Trametinib (Mekinist): This drug has been shown to cause some melanomas with BRAF changes to shrink. It is a pill taken once a day. Common side effects include rash, diarrhea, and swelling. Rare but serious side effects can include heart damage, loss of vision, lung problems, and skin infections.

When used by itself, this drug does not seem to help shrink as many melanomas as the BRAF inhibitors (although it can still help some people). Another approach is to combine it with a BRAF inhibitor in the hope of causing tumors to shrink for longer periods of time. Study results combining this drug with dabrafenib have been promising, showing that some side effects (such as the development of other skin cancers) are actually less common with the combination.

Drugs that target cells with changes in the C-KIT gene

A small portion of melanomas have changes in a gene called C-KIT that help them grow. These gene changes are more common in melanomas that start in certain parts of the body:

  • On the palms of the hands, soles of the feet, or under fingernails (known as acral melanomas)
  • Inside the mouth or other mucosal (wet) areas
  • In areas that get chronic sun exposure

Some targeted drugs used to treat other cancers, such as imatinib (Gleevec) and nilotinib (Tasigna), are known to affect cells with changes in C-KIT. If you have a melanoma that started in one of these places, your doctor may test your melanoma cells for changes in the C-KIT gene, which might mean that one of these drugs could be helpful. Clinical trials are now looking to see if these and other drugs might help people with these types of melanoma.

Drugs that target different gene changes are also being studied in clinical trials (see “What’s new in research and treatment of melanoma of the skin?”).

Last Medical Review: 10/29/2013
Last Revised: 09/05/2014