Treatment of Melanoma

Skin Cancer
Jenny Markell, Cancer Prevention and Treatment Fund

Melanoma is the most serious form of skin cancer. If caught early, melanoma has high cure rates. But, after it has spread, it can be very difficult to treat successfully. While melanoma accounts for only 2% of skin cancers, it causes more deaths than any other type of skin cancer.[1,2]

Patients with melanoma have various treatment options. The type of treatment is based on individual circumstances such as stage of disease, genetic influences, rate of tumor growth, thickness, whether cancer has spread, and overall health. Standard treatments are available, as are clinical trials using experimental treatments.

Standard melanoma treatments include:

  • Surgery
  • Chemotherapy
  • Radiation Therapy
  • Targeted Therapy
  • Immunotherapy

Surgery

Surgery to remove the tumor is often the primary treatment for early-stage melanoma.[3] The surgery removes all of the cancer and some of the healthy tissue surrounding it. The amount of scarring and the size of the excision will depend on the thickness of the tumor.[4]

In order to see whether the cancer has spread to the lymph nodes, a biopsy is needed. A sentinel lymph node biopsy with lymph node mapping may be chosen.[5] During this procedure, the physician injects a blue dye and/or radioactive substance near the tumor. The substance flows to the lymph nodes, and the first lymph node to receive the dye is removed. This is often the sentinel lymph node. A pathologist then biopsies the removed lymph node to see whether or not cancer has spread to the lymph nodes. If cancer cells are found, a lymphadenectomy, also known as lymph node dissection, is performed and more lymph nodes are removed and checked for cancer.[5]

Even if doctors remove all cancer that they see during the surgery, chemotherapy may be given to patients after surgery to ensure that the cancer doesn’t come back. This is called adjuvant therapy.[5]

If the cancer has spread to other organs (metastized), surgery is not likely to cure the cancer. However, in some cases surgery is done on patients with metastatic melanoma to try to slow down the spread of cancer.

In all cases, be sure to talk to the doctor and make sure you understand the benefits and risks of any suggested treatments.

Chemotherapy

Chemotherapy (chemo) are the drugs used to try to kill the cancer cells. The drugs can be taken in a pill or injected into a vein. Chemotherapy is called systemic therapy because the drugs can enter the bloodstream and reach cancer cells in all parts of the body.[4]

Regional chemotherapy is when the drugs are injected directly into the cerebrospinal fluid, an organ, or a body cavity to target the cancer cells in that specific area. Isolated limb perfusion is a common type of regional chemotherapy used to treat melanoma that is confined to the arm or leg. The blood flow of the arm or leg is temporarily separated from the rest of the body with a tourniquet, and chemotherapy drugs are targeted to that one region.[5]

Chemotherapy is not as effective for advanced melanoma as it is for other types of cancers and is not normally the primary form of treatment.  Common side effects of chemotherapy include hair loss, fatigue, and nausea. Side effects tend to go away after treatment is completed.

Radiation Therapy

Radiation therapy uses x-rays, or other types of rays, to stop cancer cells from growing or to kill them. External beam radiation, which is used to treat melanoma, uses a machine outside the body to send radiation onto the tumor.[3]

Targeted Gene Therapy

With greater understanding of how melanoma cells differ from other cells, researchers have developed therapies that target the gene changes (mutations) in melanoma cells. Targeted therapy drugs are different from chemotherapy drugs because rather than attacking all dividing cells, they only attack the cells undergoing these specific mutations.

  • Researchers have discovered that 50 percent of patients with melanoma have mutations in the BRAF gene, making it the most common mutation in melanoma.[6] Drugs have been developed to target this specific gene and related proteins.
  • The FDA has approved two drugs in the past 5 years for people with BRAF mutant metastatic melanoma: Vemurafenib (Zelboraf) and Dabrafenib (Tafinlar). They have shown to improve the length of survival in about half of patients with BRAF mutant melanoma.
  • Drugs that block MEK proteins have also been shown to help patients with BRAF mutant melanoma. The FDA approved Trametinib (Mekinist) in 2013, which targets MEK, for people with BRAF mutant melanoma.[6]
  • Recently, studies have shown that using a combination of BRAF and MEK targeted therapies is more effective than therapies using only one of these treatments.[7]

Targeted therapies have increased survival rates by a number of months, but have only delayed rather than cured the cancer. However, these treatments are all very new and many studies are underway to try to find a longer-term solution to metastatic melanoma.

 

Immunotherapy

Immunotherapy, also called biologic therapy, uses the patient’s immune system to help fight the cancer. Several different types of immunotherapy are used to treat melanoma:

  • Interferon alpha and Interleukin-2 were both approved by the FDA in the 1990s and a small percentage of patients have benefited greatly from their use. However, they also can have severe side effects.[3]
  • Ipilimumab was approved by the FDA in 2011 and helps boost the immune system by targeting a protein on T-cells. This has helped patients live up to a few months longer, on average.[8]

There have recently been major advances in clinical trials for immunotherapy treatment for melanoma. An April 2015 study in the New England Journal of Medicine found that a combined immunotherapy treatment may extend length of survival even further.[9]

 

Clinical Trials

Clinical trials are used to help find new treatments for cancer. These are experiments that can help patients or harm them. Patients can enter clinical trials at different stages of their cancer treatment, but some trials may only be open to patients who have not yet started other treatment. Click here for NCI’s list of clinical trials

References:

  1. Cancer.Net. “Melanoma: Statistics.” Accessed June 04, 2015. http://www.cancer.net/cancer-types/melanoma/statistics High exposure to UV radiation from sunlight or tanning beds can greatly increase one’s risk of developing melanoma.
  2. Mayo Clinic. Melanoma: Definition.” Accessed June 05, 2015. http://www.mayoclinic.org/diseases-conditions/melanoma/basics/definition/con-20026009
  3. Mayo Clinic. “Melanoma: Treatments and drugs.” Accessed June 04, 2015. http://www.mayoclinic.org/diseases-conditions/melanoma/basics/treatment/con-20026009.
  4. American Cancer Society. “How is Melanoma Cancer Treated?” Accessed Jun 04, 2015. http://www.cancer.org/cancer/skincancer-melanoma/detailedguide/melanoma-skin-cancer-treating-surgery.
  5. National Cancer Institute. “Melanoma Treatment.” Accessed June 04, 2015. http://www.cancer.gov/types/skin/patient/melanoma-treatment-pdq#section/_135
  6. Kudchadkar, R.R., Smalley, K.S.M., Glass, L.F., Trimble, J.S and Sondak, V.K. (2013). Targeted Therapy in Melanoma. Clinics in Dermatology 31(2): 200-208.
  7.  Long, G.V., Stroyakovskiy, H., Gogas, H. et al. (2014). Combined BRAF and MEK Inhibition versus BRAF Inhibition Alone in Melanoma. N Engl J Med. 371(20): 1877-1888.
  8. National Cancer Institute. “FDA Approval for Ipilimumab.” Accessed June 04, 2015. http://www.cancer.gov/about-cancer/treatment/drugs/fda-ipilimumab.
  9. Michael A. Postow, Jason Chesney, Anna Pavlick, Caroline Robert, Kenneth Grossmann, David McDermott, Gerald Linette, Nicolas Meyer, Jeffrey Giguere, Sanjiv Agarwala, Montaser Shaheen, Marc S. Ernstoff, David Minor, April K. Salama, Matthew Taylor, Patrick A. Ott, Linda M. Rollin, Christine Horak, Paul Gagnier, Jedd D. Volchok, and F. Stephen Hodi. Nivolumab and Ipilimimumab versus Ipilimumab in Untreated Melanoma. New England Journal of Medicine 373: 23-34.