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Treatment Options for Stage III Melanoma

After your stage of melanoma has been identified, your doctor will discuss a plan of treatment with you. It is important to understand if all of your Stage III melanoma has been completely removed with surgery (resected Stage III) or if it was not possible to remove all of the melanoma (unresectable Stage III). These two variations of Stage III melanoma are treated very differently. Unresectable Stage III patients are treated similarly to Stage IV melanoma patients.

 

Treatment
Goal 

Surgery

To remove any cancer remaining after the biopsy of the primary melanoma. The procedure is called a wide local excision. Wide local incision is recommended for small, easily removable recurrent tumors and for patients with a limited number of in-transit tumors.

 

The surgeon removes the tumor, including the biopsy site, as well as a surgical margin, (a surrounding area of normal-appearing skin), and underlying subcutaneous tissue.

 

Most surgeons today follow the guidelines adopted and recommended by the National Institutes of Health and the World Health Organization Melanoma Program.

  • The recommended margins for wide local excision of the primary melanoma ranges from 1-2 cm and is determined by the thickness of the primary melanoma.

Lymph Node Dissection

When cancerous lymph nodes are found and there is evidence that the melanoma has spread to nearby lymph nodes, an additional surgery to remove the remaining lymph nodes from the area is usually recommended. If your melanoma was found by sentinel lymph node biopsy this is called a complete lymph node dissection (CLND). If your melanoma was found because your lymph nodes were enlarged, this is called a therapeutic lymph node dissection (TLND.

 

The goal of the surgery is to prevent further spread of the disease through the body by way of the lymphatic system. Current studies are underway to determine whether CLND and TLND may also prolong survival.

 

CLND and TLND also play an important role in controlling the pain often caused by untreated lymph node disease. 

Sentinel Lymph Node 

Biopsy

(SLNB)

If a patient has already been diagnosed with Stage III melanoma, a sentinel lymph node biopsy is typically recommended only for patients where it is suspected that there might be melanoma in another lymph node basin.

 

The results of the biopsy will guide the course of treatment.

 

For more on sentinel lymph node biopsy click here.

Adjuvant Therapy

Systemic treatment, given after surgery to remove all the melanoma, is often recommended for Stage III melanoma. These systemic therapies go throughout the bloodstream in an effort to reach and destroy any remaining cancer cells throughout the body.

 

Interferon is a protein produced by normal cells to fight viral infections and disease. There are now two types of interferon that have been approved by the Food and Drug Administration (FDA) for Stage III melanoma: high-dose interferon (Intron A) and pegylated interferon (Sylatron).

 

Purpose and Effectiveness
  • Interferon therapies have been shown to help the body's immune system fight disease more effectively.
  • High- dose interferon alfa-2b significantly prolongs disease-free survival in patients with Stage III melanoma. It has not been shown to prolong overall survival. The drug has to be administered frequently, over a period of a year, at a very high doses in order to be effective. Pegylated interferon alfa-2b is designed to provide high levels of interferon in the blood when given by subcutaneous injection once a week for at least one year, and up to 5 years. This has shown to prolong disease-free survival but has not been shown to prolong overall survival.

Treatment Side Effects
Other Treatment Options

Clinical trials - There are several clinical trials evaluating different treatments in the adjuvant therapy of melanoma. This includes medicines that are already FDA-approved for more advanced melanoma, such as ipilimumab, dabrafenib, vemurafenib and trametinib.

 

FOR UNRESECTABLE STAGE III MELANOMA:

 

A)     Ipilimumab (brand name: Yervoy) is a monoclonal antibody that has been approved by the FDA for the treatment of unresectable or metastatic melanoma. Unresectable melanoma is such that all sites of melanoma tumors cannot be completely removed surgically.

 

  • Ipilimumab is designed to restore and strengthen the immune system by successfully activating T-cells (T lymphocytes), a critical component of the immune system, with the hope to  sustain an active immune response to fight the cancer cells for a long time.
  • Studies indicate that it improves overall median survival by 4 months.


Treatment Side Effects

 

B)     Vemurafenib (brand name: Zelboraf) and Dabrafenib (brand name: Tafinlar) are tyrosine kinase inhibitors that have been approved by the FDA for the treatment of patients with unresectable or metastatic melanoma that have a BRAF V600E mutation.

 

Purpose and Effectiveness

  • The BRAF gene and protein is normally involved in regulating cell growth, but is mutated in about half of patients with melanoma. vemurafenib and dabrafenib work by blocking the function of the V600E-mutated BRAF protein.
  • In a trial comparing vemurafenib to dacarbazine (chemotherapy) in patients with the BRAF V600E mutation, the dacarbazine group had a response rate (shrinkage rate of 5% with 64% still living at 6 months. In the vemurafenib group, the response rate was 48% with 84% still living at 6 months.
  • In a trial comparing dabrafenib to dacarbazine (chemotherapy) in patients with the BRAF V600E mutation, the dabrafenib group had progression free survival (the time a patient lives without cancer growing or spreading) of 5.1 months compared to 2.7 months for those on dacarbazine.

 

Treatment Side Effects

 

C)    Trametinib (brand name: Mekinist) is a kinase inhibitor that inhibits another protein, named MEK, and has been approved by the FDA for the treatment of patients with unresectable or metastatic melanoma that have a BRAF V600E or BRAF V600K mutation.  Trametinib has not shown benefit when used by patients who have already taken a BRAF inhibitor and their melanoma is no longer sensitive.

 

Purpose and Effectiveness

  • The BRAF protein is normally involved in regulating cell growth, but is mutated in about half of the patients with late-stage melanomas. Mekinist works by blocking the function of the MEK protein, which is overactive inV600E-mutated or V600K-mutated melanoma.
  • In a trial comparing trametinib to chemotherapy (dacarbazine or paclitaxel) in patients with metastatic melanoma with a BRAF V600E or BRAF V600K mutation, the trametinib group had improved overall survival compared with chemnotherapy.

 

Treatment Side Effects

 

D)     Dabrafenib in combination with Trametinib

 

Purpose and Effectiveness

  • In a phase I/II trial comparing dabrafenib alone to dabrafenib with trametinib in patients with BRAF V600E or V600K mutations, the combination group had a response rate (tumor shrinkage rate) of 76% which lasted for 10.5 months versus a response rate of 54% that lasted for 5.6 months in the dabrafenib only group. There is an ongoing phase III study to evaluate the combination treatment versus single agent dabrafenib but the results are still pending at this time. The FDA granted accelerated approval for the use of combination therapy.

 

Treatment Side Effects

  • coming soon

Radiation Therapy

Radiation therapy in the adjuvant setting has been shown to improve local control (control melanoma in the lymph node basin) but has not been proven to improve overall survival (keep melanoma from coming back elsewhere in the body) in randomized, controlled studies.

 

For more information on radiation therapy click here.

Clinical Trials

Clinical trials are research studies to evaluate new therapies and improve cancer care. These studies are responsible for most of the advances in cancer prevention, diagnosis, and treatment. If you have melanoma, you may be eligible to participate in a clinical trial.

 

See the section on clinical trials in the Stage IV melanoma section for more information.

 

For more information on clinical trials click here.

 

For more information on Stage III follow-up click here.



FAST FACTS

What is adjuvant therapy?

It is treatment that is given in addition to the primary cancer treatment. For melanoma, this means medicines given after surgical removal of all sites of melanoma. It involves using substances that travel through the bloodstream and attack cancer cells located in the body.

 

One of these treatments is interferon, a protein produced by normal cells in the body that fight viruses and disease. High doses of interferon alpha-2b is the only treatment available that helps the immune system fight the disease while offering relapse-free survival and possible improvement in overall survival.