Melanoma

Is your treatment what more than 1,100 Oncologists recommend?

The information provided below is meant to help you understand the role of your melanoma biology in treatment decisions, as well as the role of other tools used in determining your ability to receive chemotherapy or targeted therapy (precision medicine).

In 2016, there are 76,380 new cases of melanoma in the United States (CA Cancer J Clin 2016; 66(1):7-30) and its incidence has increased three times over the last two decades. Melanoma can occur in any ethnic group and 1/37 men (1/56 women) will be diagnosed with melanoma in their lifetime.

Risk Factors

• The genetic factors: in individuals with family history of melanoma (10% of melanoma is hereditary), the most common gene is CDKN2A mutation (also risk for pancreatic cancer) and BRCA2 gene mutation (also risk for breast and ovarian cancers), and risk in individuals with multiple atypical moles
• The environmental factors: in individuals with fair skin that burn, behavior such as excessive sun exposure with UV light (UVB is worse than UVA)

In melanoma, the stage when you first diagnosed predicts outcome. Information such as tumor thickness in mm, number of positive lymph nodes and mitotic index (measure of cell growth) help predict survival in affected individuals. Melanoma lesions in extremities can have better outcome than those of trunks and head.

Treatment

Three different approaches to treating melanoma are available.

• Resection surgery (if indicated)
• Radiation (if needed)
• Immunotherapy, targeted therapy (precision medicine) and chemotherapy

This website is designed to outline in detail your targeted therapy options and offer you personalized information about the best options to yield optimal survival and quality of life. Multiple factors affect your treatment options including:

• Cancer is recurring (you have had melanoma before) or your cancer is a first time diagnosis: The treatment for recurrence is determined by what type of treatment you received for your first diagnosis. Certain treatment can only be given once in your lifetime.
• The molecular characteristics of your melanoma (tumor biology) will greatly affect treatment decisions
• Cancer stage at the time of the diagnosis. Your treating physicians will do imaging tests (CT, bone scan or PET/CT) to determine your stage

Stages in melanoma

• Stages I and II (in 80% of all melanoma) are localized to the skin
• Stage III (in 15% of all melanoma) has lymph nodes involvement
• Stage IV or advanced melanoma ( in 5% of all melanoma) spreads to other parts of the body

Exciting new targeted therapies for advanced melanoma treatment are available since 2011.Your tumor is used to test for these markers.

BRAF inhibitors drugs

BRAF gene mutations (V600) are seen in 50-60% of melanoma and produces B-Raf protein (transmit chemical signals for abnormal cell growth). The BRAF inhibitor drugs such as Vemurafenib or Dabrafenib are used if your melanoma expresses mutated BRAF. These drugs have more than 50% chance for response.

MEK inhibitor drugs

Despite an initial excellent response, half of the patients experience progression eventually on BRAF inhibitor drugs. MEK pathway is a chain of proteins that communicate signals from the surface to the nucleus of the cells. When patients with mutated BRAF no longer respond to BRAF inhibitors drugs (Vemurafenib or dabrafenib), MEK inhibitor pathway drugs (Trametinib, Cobimetinib) can control tumor.

Combination of both BRAF and MEK inhibitors have even higher response rate about 70% of tumor control. Two combinations are currently available trametinib/dabrafenib and cobimetinib/vemurafenib. The combination approach is now used as the front line therapy in patients who harbor BRAF mutation.

Immunotherapy

Immunotherapy is used to unleash your own immune system to fight tumor and has resulted in significant improvement in survival in advanced melanoma.

• Direct block to “cytotoxic T lymphocyte antigen-4″ (CTLA-4) with the drug called ipilimumab (Yervoy) results in activation of T -cells (cells that play an essential role in immunity) to fight tumors
• Program death (PD-1 protein) helps tumors escape the immune system. Thus, by blocking PD-1 path with PD-1 inhibitors drugs such as nivolumab (Opdivo) or pembrolizumab (Keytruda), it activates T-cells to fight melanoma
• IL-2 activates T-cell response and is only used in selected cases of melanoma due to its high toxicity and low response, however, the response is long lasting

Chemotherapy

Chemotherapy has limited response in melanoma. The chemotherapy drugs are dacarbazine, temozolamide, carboplatin/paclitaxel that can be used in advanced melanoma.

This website gives you about 80-85% of straight forward melanoma treatment plans. All melanoma treatment are recommended based on expertise ‘s opinions from multiple national guidelines (NCCN, ASCO, ESMO, ASTRO). For recurrent advanced melanoma, the website will give you the best recommended treatment plans.

Even though the standard of treatment is outlined, your individual tolerability to each treatment will depend on your overall health, i.e. whether you have other illness (diabetes, heart disease, liver disease, arthritis, or kidney disease). Another assessment that your treating physicians may use to determine the optimal melanoma treatment plan and prognosis for you is called ECOG performance status as described below.

ECOG PERFORMANCE STATUS

Grade 0: Fully active, able to carry on all activity
Grade 1: Restricted in physically strenuous activity but ambulatory and able to carry out light house work, office work
Grade 2: Ambulatory and capable of all self-care but unable to carry out any work activities
Grade 3: Capable of only limited self-care, confined to bed or chair more than 50% of waking hours
Grade 4: Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair

(Am J Clin Oncol 1982: 5: 649-655)

Finally, chemotherapy and targeted therapies can result in unpleasant side effects such as hair loss, numbness of fingers or toes, cardiac toxicity, nausea, vomiting, diarrhea, abnormal liver function or low white blood cell count that could cause infection, and fatigue. However, advances in the oncology field have led to numerous supportive measures, such as white blood cell growth support (i.e. Neulasta) or anti-nausea medications (such as Zofran), that help to control most side effects when used as prescribed.

The best time to use this service (based on more than 1,100 cancer experts) is after you have learned the details of your cancer and treatment plan from your treating physicians, and would like to clarify and confirm that your treatment is the best option for your cancer.  This questionnaire is used mainly for drug treatment in medical oncology.