Medications to Treat Melanoma
The following chemotherapies and immune therapies are approved by the Food and Drug Administration (FDA) for the treatment of melanoma at various stages:
Deep Stage II and Stage III Melanoma
- High Dose Interferon Alpha-2b: Administered intravenously five days a week for four weeks and then as an injection into subcutaneous tissue three times a week for 11 months.
- Pegylated Interferon: Weekly injections for five years. Approved only for stage III melanomas, interferon alpha was studied in several large studies and more consistently delays the time to relapse by approximately one year.
Several studies (ECOG 1684 and ECOG 1694) demonstrated overall survival (living longer benefit) following treatment with interferon alpha, but this benefit is no longer seen after 12.6 years of follow-up. Therefore the living longer benefit appears to be lost over time.
Stage IV Melanoma
- Dacarbazine (DTIC): A chemotherapy administered by vein often once every three weeks. It acts by modifying and damaging the DNA. The response rate to treatment with DTIC is under 20 percent. There is no proven overall survival benefit to this treatment.
- High Dose Interleukin-2 (HD-IL2): An immune treatment that activates T-cells to help the immune system fight the melanoma. Patients are admitted to the hospital for this treatment. Side effects can be significant and need intensive monitoring. The response rate is 16 percent, but approximately five percent of patients develop complete durable responses.
- Ipilimumab (Yervoy): A novel immune treatment approved by the FDA in March 2011. It is an antibody that binds to a protein called CTLA-4, which is present on certain types of immune cells. This treatment is administered by vein once every three weeks for four treatments. It works by “taking the breaks off” your immune system in order to let your immune system attack the melanoma. This treatment has the potential to create very durable responses, and treatment has overall survival benefits.
In order to understand how this treatment works, consider what happens to your immune system when you develop an infection. Your immune system is activated to fight the infection. Once the infection is treated the immune system then starts to shut itself off. In order to do this a type of immune cell called the suppressor T-cell, which suppresses the immune system, starts to express on its surface CTLA-4, which then binds to proteins such as B7 found on other immune cells to suppress their activity. Ipilimumab binds to CTLA-4 and prevents CTLA-4 from doing its job as it can no longer bind effectively to other proteins such as B7. As such, the immune system is not suppressed and remains active.
- Vemurafenib (Zelboraf): A novel "targeted therapy" approved by the FDA in August 2011. Vemurafenib is administered orally two times a day every day. It blocks a protein called BRAF, which is mutated and activated in approximately 50 percent of melanomas. BRAF is part of a signaling pathway called the Mitogen Activated Protein Kinase (MAPK) pathway. When the MAPK pathway is activated, cells are better able to divide and stay alive. In melanoma, over 90 percent of activating mutations in BRAF occur at portion 600 of the protein, and the most common mutation is called a V600E BRAF mutation. Such mutations are seen in the majority of melanomas that arise on skin surfaces that are only intermittently exposed to the sun (such as the chest and back) but still can be detected with lower incidence in melanomas arising on chronic sun-exposed skin (head and neck), mucosal surfaces, and the palms, soles, and finger nails.
The response rate to treatment with vemurafenib in patients whose melanoma expresses a V600E BRAF mutation is approximately 50 percent, and a significant overall survival benefit is seen with this treatment. These benefits are not seen in melanomas lacking mutations in BRAF.