What A is the drug that is effective in the treatment of malignant or cancerous disease?

Chemotherapy is one of the most common treatments for cancer. It uses certain drugs to kill cancer cells or to stop them from growing and spreading to other parts of your body. Your doctor might prescribe chemo by itself or with surgery or radiation therapy. You might also take newer kinds of cancer-fighting drugs along with chemotherapy.

You can take chemo as pills or shots. You might go to a clinic or hospital so you can get the drugs through an IV, what doctors call an infusion.

To help your body regain strength and grow new, healthy cells, you might take the drugs over a few weeks. You might take doses every day, every week, or every month. It depends on the type of cancer you have and how severe it is.

Your cancer doctor, called an oncologist, may prescribe one chemo drug or a mix of different ones, depending on:

  • Your type of cancer
  • Whether you’ve had cancer before
  • If you have other health problems like diabetes or heart, kidney, or liver disease

Even after surgery to remove a tumor, your body might still have cancer cells. These cells can grow new tumors or spread the cancer to other parts of your body.

Chemotherapy drugs help destroy, shrink, or control those cells. It might also treat symptoms the cancer causes, like pain. You might also get chemo to shrink a tumor before your doctor removes it in surgery.

Chemotherapy drugs work in a few different ways. They can:

  • Kill both cancerous and healthy cells
  • Fight only cancer cells
  • Keep tumors from growing blood vessels, which help them thrive
  • Attack the cancer cells’ genes so the cells die and can’t grow into new tumors

There are dozens of chemotherapy drugs that doctors can prescribe. They’re often divided into groups based on how they work and what they’re made of. Each group of drugs destroys or shrinks cancer cells in a different way.

  • Some drugs damage the DNA of cancer cells to keep them from making more copies of themselves. They are called alkylating agents, the oldest type of chemotherapy. They treat many different types of cancer, such as leukemia, lymphoma, Hodgkin's disease, multiple myeloma, and sarcoma, as well as breast, lung, and ovarian cancers. Some examples of alkylating agents are cyclophosphamide, melphalan, and temozolomide. As they kill bad cells, though, they can also destroy your bone marrow in the process, which can cause leukemia years later. To lower this risk, you can take the drugs in small doses. One type of alkylating agent -- platinum drugs like carboplatin, cisplatin, or oxaliplatin -- has a lower risk of causing leukemia.
  • One type of chemo drug interferes with the normal metabolism of cells, which makes them stop growing. These drugs are called antimetabolites. Doctors often use them to treat leukemia and cancer in the breasts, ovaries, and intestines. Drugs in this group include 5-fluorouracil, 6-mercaptopurine, cytarabine, gemcitabine, and methotrexate, among many others.
  • Anthracycline chemotherapy attacks the enzymes inside cancer cells’ DNA that help them divide and grow. They work for many types of cancer. Some of these drugs are actinomycin-D, bleomycin, daunorubicin, and doxorubicin, among others. High doses of anti-tumor antibiotics can damage your heart or lungs. So your doctor will have you take them for a short time.
  • Drugs called mitotic inhibitors stop cancer cells from making more copies of themselves. They can also stop your body from making the proteins that cancer cells need to grow. Doctors might prescribe them for breast and lung cancers and types of myeloma, leukemia, and lymphoma. Mitotic inhibitors include docetaxel, estramustine, paclitaxel, and vinblastine.
  • Another type of medicine, called topoisomerase inhibitors, also attacks enzymes that help cancer cells divide and grow. They treat some types of leukemia and cancer of the lung, ovaries, and intestines, among other types. This group of medicine includes etoposide, irinotecan, teniposide, and topotecan. Some of them, though, may raise your odds of getting a second cancer a few years later.
  • Steroids are drugs that act like your body’s own hormones. They are useful in treating many types of cancer, and they can keep you from having nausea and vomiting after a round of chemo. They can also prevent allergic reactions to some of the drugs. Some of the steroids your doctor might prescribe are prednisone, methylprednisolone, and dexamethasone.

Chemotherapy is a common cancer treatment, but today, doctors often prescribe other kinds of cancer medicines, such as targeted therapies, hormone therapy, and immunotherapy. Unlike chemo, these types of medicine are better at attacking only cancer cells and leaving healthy cells alone. That means they cause milder side effects. Your doctor might recommend that you take them along with chemo drugs or on their own.

Your oncologist will watch your body’s response during and after treatment.

Oncologists look for signs that your tumor is shrinking or growing. They use tests like physical exams, blood tests, or CT scans.

If your treatment doesn’t seem to be working, the oncologist might give you a different dose or a mix of other treatments.

ON THIS PAGE: You will learn about the different types of treatments doctors use to treat people with melanoma. Use the menu to see other pages.

This section explains the types of treatments, also known as therapies, that are the standard of care for melanoma. “Standard of care” means the best treatments known. When making treatment plan decisions, you are encouraged to discuss with your doctor whether clinical trials are an option. A clinical trial is a research study that tests a new approach to treatment. Doctors learn through clinical trials whether a new treatment is safe, effective, and possibly better than the standard treatment. Clinical trials can test a new drug, a new combination of standard treatments, or new doses of standard drugs or other treatments. Clinical trials are an option for all stages of cancer. Your doctor can help you consider all your treatment options. Learn more about clinical trials in the About Clinical Trials and Latest Research sections of this guide.

The cancer care team

In cancer care, different types of health care professionals often work together to create a patient’s overall treatment plan that combines different types of treatments. This is called a multidisciplinary team. Cancer care teams include a variety of important health care professionals, including doctors, physician assistants, nurse practitioners, oncology nurses, social workers, pharmacists, counselors, dietitians, and others.

People with melanoma my work with doctors in different specialties. These include:

  • Dermatologist: A doctor who specializes in diseases and conditions of the skin.

  • Surgical oncologist: A doctor who specializes in treating cancer with surgery.

  • Medical oncologist: A doctor who specializes in treating cancer with medication.

  • Radiation oncologist: A doctor who specializes in treating cancer with radiation therapy.

  • Pathologist/Dermatopathologist: A doctor who specializes in interpreting laboratory tests and evaluating cells, tissues, and organs to diagnose disease. A dermatopathologist is a pathologist with additional training who specializes in diseases of the skin.

  • Radiologist: A medical doctor who specializes in using imaging tests to diagnose disease.

How melanoma is treated

Treatment recommendations for melanoma depend on many factors, including the thickness of the primary melanoma, whether the cancer has spread, the stage of the melanoma, the presence of specific genetic changes in melanoma cells, rate of melanoma growth, and the patient’s other medical conditions. Other factors used in making treatment decisions include possible side effects, as well as the patient’s preferences, overall health, goals for treatment, and quality of life. This section provides an overview of possible treatments and should not be considered treatment recommendations for individuals.

Take time to learn about all of your treatment options and be sure to ask questions about things that are unclear. Talk with your doctor about the goals of each treatment and what you can expect while receiving the treatment. These types of talks are called “shared decision-making.” Shared decision-making is when you and your doctors work together to choose treatments that fit the goals of your care. Shared decision-making is particularly important for melanoma because there are different treatment options. Learn more about making treatment decisions.

The common types of treatments used for melanoma are described below. Later in this section, treatments are listed according to the stage of melanoma. Your care plan may also include treatment for symptoms and side effects, an important part of cancer care.

Surgery

Surgery is the removal of the tumor and some surrounding healthy tissue during an operation. This procedure is usually performed by a surgical oncologist.

Surgery is the main treatment for people with local melanoma and most people with regional melanoma. For some people with metastatic melanoma, surgery may also be an option. If surgery is not an option, the melanoma may be called “unresectable.” In recommending a specific treatment plan, doctors will consider the stage of the disease and the person’s individual risk of recurrence.

Three types of surgery used to treat local and regional melanoma are wide excision, lymphatic mapping and sentinel lymph node biopsy, and lymph node dissection. Each is explained below in more detail.

Before surgery, talk with your health care team about the possible side effects from the specific surgery you will have. Learn more about the basics of cancer surgery.

Wide excision

The main treatment for melanoma is surgical removal, or excision, of the primary melanoma on the skin. The extent of the surgery depends on the thickness of the melanoma. Most melanomas are found when they are less than 1.0 mm thick, and outpatient surgery is often the only treatment needed. A doctor removes the tumor, tissue found under the skin, and some surrounding healthy tissue, called a margin, so that no cancer cells remain. If a sentinel lymph node biopsy is also performed, it is usually done at the same time as the wide excision (see Diagnosis and below).

  • If the melanoma is staged as in situ (stage 0), the doctor may remove a margin of skin at least 5 mm (or 0.5 cm) around the cancer. Overall, the width of the margin increases with the thickness of the melanoma, ranging from a 1-cm margin for melanoma measuring up to 1.0 mm to a 2-cm margin for melanoma measuring over 2 mm.

  • Depending on the site and extent of the surgery, a skin flap or a skin graft may be necessary. A skin flap is created when nearby tissue is moved around to cover the area removed during surgery. A skin graft uses skin from another part of the body to close the wound.

Lymphatic mapping and sentinel lymph node biopsy

During this surgical procedure, the surgeon injects the area of the tumor with a dye and a radioactive tracer. This is to figure out which lymph nodes might be involved and whether the melanoma has spread to the lymph nodes. During these procedures, the surgeon removes 1 or more lymph nodes that take up the dye and/or radioactive tracer, called sentinel lymph nodes, to check for melanoma cells. If melanoma cancer cells are not found in the sentinel lymph node(s), no further lymph node surgery is required. If the sentinel lymph nodes contain melanoma, this is called a positive sentinel lymph node. This means the disease has spread, and lymph node dissection (see below) may be discussed.

These procedures are usually recommended for people with a melanoma that is more than 0.8 mm thick or has ulceration. However, a sentinel lymph node biopsy may also be recommended by a surgical oncologist for some other melanomas that are less than 0.8 mm thick depending on other, related risk factors.

For non-ulcerated melanomas less than 0.8 mm thick, the likelihood that the cancer has spread to the lymph nodes is low, so sentinel lymph node mapping is not recommended in most cases. However, sometimes the doctor will recommend this procedure for a person with a thin, high-risk melanoma if there are other signs that the melanoma is more aggressive, such as ulceration (see Diagnosis). If the melanoma is less than 0.8 mm, your doctor will discuss whether this approach is recommended based on other features of the primary melanoma and other factors.

Sentinel lymph node mapping ideally is done at the same time as wide local excision to remove the melanoma. This is because wide local excision can change the lymphatic drainage pattern and doing both procedures at the same time means the patient only has to have 1 surgery as opposed to multiple surgeries.

Lymph node dissection

If biopsy results show that cancer is found in the sentinel lymph nodes, this is called a positive sentinel lymph node. This means the disease has spread. In the past, the removal of more lymph nodes, called complete lymph node dissection (CLND), was typically recommended. However, recent data shows that this procedure does not affect how long patients live. In most instances, close monitoring with regular physical exams and lymph node ultrasounds is recommended in place of a CLND. The number of lymph nodes removed depends on the area of the body. A patient will take longer to recover after CLND and have a higher risk of side effects. People who have had a CLND around an arm or leg have a higher risk for fluid buildup in that limb, a side effect called lymphedema. If it is recommended, talk with your doctor about the possible risks and benefits of having lymph node dissection.

This information is based on the ASCO guideline, "Sentinel Lymph Node Biopsy for Melanoma." Please note that this link takes you to another ASCO website.

Sometimes an enlarged lymph node is found during a physical exam, after a scan, or during an ultrasound. If this happens, doctors usually perform a biopsy and obtain staging scans. If no other evidence of spread is found, they may recommend a lymph node dissection. Doctors generally agree it is important to remove all lymph nodes in these situations.

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Radiation therapy

Radiation therapy is the use of high-energy x-rays or other particles to destroy cancer cells. The most common type of radiation treatment is called external-beam radiation therapy, which is radiation given from a machine outside the body. The radiation beam produced by this machine can be pointed in different directions and blocked using special techniques to help decrease side effects. The radiation oncologist will recommend a specific radiation therapy regimen, or schedule, with a total number of treatments and dose of radiation.

Sometimes, radiation therapy is recommended after surgery to prevent the cancer from coming back, called a recurrence. Radiation therapy given in this manner is called adjuvant radiation therapy. Research has shown that although this may reduce the risk of the melanoma coming back in the area that received radiation, it does not increase how long a person lives. People who receive adjuvant radiation therapy experience side effects based on which area of the body was treated. In general, a person’s overall quality of life is similar to that of people who do not receive adjuvant radiation therapy, according to the results of recent clinical trials. However, in those studies, some patients who received adjuvant radiation therapy had worse symptoms in the first year.

If melanoma has spread and causes symptoms, such as bone pain or headaches, then radiation therapy may help relieve those symptoms. This is called palliative radiation therapy. For some people, palliative radiation therapy is given to an entire organ with several small doses of radiation, such as to the entire brain using whole-brain radiation therapy. Other times, 1 or just a few high doses of radiation therapy are given using a linear accelerator (or "linac," for short), Gamma Knife, CyberKnife, or TomoTherapy unit. This is called stereotactic radiosurgery, stereotactic ablative radiation therapy, or stereotactic body radiation therapy. It usually works best for just 1 or a few tumors in the brain or elsewhere in the body.

Radiation therapy may be used when cancer has extensive spread to the lymph nodes or skin and cannot be removed by surgery. Researchers also are testing the effectiveness of combining radiation therapy and medicines for melanoma.

Learn more about the basics of radiation therapy.

Side effects of radiation therapy

General side effects of radiation therapy include skin irritation, skin infections, and fatigue. These usually get better a few weeks after radiation therapy is finished. Topical corticosteroid creams and antibiotics may be used to help prevent and treat radiation-induced skin reactions.

Depending on the area of the body being treated with radiation therapy, other side effects may develop. For example, after treatment to the head and neck region, temporary irritation of the mouth or difficulty swallowing can occur. If treatment was directed at the armpit or groin area, the person may have higher risk of lymphedema. Lymphedema can be a long-term, ongoing side effect. Talk with the radiation oncologist to learn more about the possible side effects that you may experience and how they can be managed.

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Therapies using medication

The treatment plan may include medications to destroy cancer cells. Medication may be given through the bloodstream to reach cancer cells throughout the body. When a drug is given this way, it is called systemic therapy. Medication may also be given locally, which is when the medication is applied directly to the cancer or kept in a single part of the body.

This treatment is generally prescribed by a medical oncologist, a doctor who specializes in treating cancer with medication.

Medications are often given through an intravenous (IV) tube placed into a vein using a needle or as a pill or capsule that is swallowed (orally). If you are given oral medications, be sure to ask your health care team about how to safely store and handle them.

The types of medications used for melanoma include:

  • Immunotherapy

  • Targeted therapy

  • Chemotherapy

Each of these types of therapies is discussed below in more detail. A person may receive 1 type of medication at a time or a combination of medications given at the same time. They can also be given as part of a treatment plan that includes surgery and/or radiation therapy.

The medications used to treat cancer are continually being evaluated. Talking with your doctor is often the best way to learn about the medications prescribed for you, their purpose, and their potential side effects or interactions with other medications.

It is also important to let your doctor know if you are taking any other prescription or over-the-counter medications or supplements. Herbs, supplements, and other drugs can interact with cancer medications, causing unwanted side effects or reduced effectiveness. Learn more about your prescriptions by using searchable drug databases.

The information about therapies using medication for melanoma are based on the ASCO guideline, “Systemic Therapy for Melanoma.” Please note that this link takes you to another ASCO website.

Immunotherapy

Immunotherapy uses the body's natural defenses to fight cancer by improving your immune system’s ability to attack cancer cells. Learn more about the basics of immunotherapy.

In recent years, there have been major advances in treating stage II, stage III and stage IV melanoma with immunotherapy. Although immunotherapy can be effective at treating melanoma, there are many possible side effects of the treatment. Different types of immunotherapy can cause different side effects. Common side effects include skin reactions, flu-like symptoms, diarrhea, and weight changes. Learn more about the side effects of immunotherapy.

Talk with your doctor about possible side effects for the immunotherapy recommended for you.

PD-1 and PD-L1 inhibitors

In immunotherapy for melanoma, there are 2 monoclonal antibodies that block a protein called programmed death-1 (PD-1) that have been approved by the U.S. Food and Drug Administration (FDA) to treat stage II, stage III, or stage IV (metastatic) melanoma: nivolumab (Opdivo) and pembrolizumab (Keytruda). PD-1 is found on the surface of T cells and interacts with a protein called PD-L1. T cells are a type of white blood cell that directly helps the body’s immune system fight disease. The PD-1/PD-L1 protein interaction keeps the immune system from destroying the cancer. Drugs that stop PD-1 and PD-L1 from working allow the immune system to better target melanoma cells.

Both nivolumab and pembrolizumab have been shown to shrink melanoma for 25% to 45% of patients with unresectable (which means surgery is not an option) or stage IV melanoma, depending on when the treatment is given. Both drugs also have been shown to reduce the risk of the cancer coming back after surgery for stage III melanoma. More recently, pembrolizumab has been shown to reduce the risk of cancer coming back after surgery for higher risk stage II melanoma (stage IIB and stage IIC). Side effects occur less frequently with nivolumab and pembrolizumab compared to ipilimumab (Yervoy, see below). ASCO recommends either nivolumab or pembrolizumab as an option to treat stage III melanoma after surgery, unresectable melanoma, and metastatic melanoma whether or not the melanoma has a BRAF mutation.

Atezolizumab (Tecentriq) is a PD-L1 inhibitor that can be used to treat advanced melanoma with a BRAF V600 mutation. Atezolizumab was approved by the FDA in 2020 to be given in combination with 2 targeted therapies: cobimetinib (Cotellic), a MEK inhibitor, and vemurafenib (Zelboraf), a BRAF inhibitor. These targeted therapies are described below.

Other PD-1 and PD-L1 inhibitors are being developed and studied.

CTLA-4 inhibitors

Ipilimumab (Yervoy) is an immunotherapy that targets a molecule called cytotoxic T-lymphocyte associated molecule-4 (CTLA-4). There have been 2 clinical trials that showed that people with unresectable or metastatic melanoma taking ipilimumab had a better chance of survival than people who only received traditional chemotherapy (see below). Ipilimumab has been shown to shrink melanoma for 10% to 15% of patients. Those responses may last years and may be permanent in many patients.

Ipilimumab is approved by the FDA to treat unresectable melanoma and metastatic melanoma. It is also approved for adjuvant treatment of stage III melanoma after surgery. Ipilimumab has been shown to have a high rate of severe, life-threatening side effects. Because of the high rate of severe side effects, ASCO does not recommend it for routine use in stage III melanoma. ASCO does recommend its use in combination with nivolumab to treat unresectable and metastatic melanoma.

The side effects of ipilimumab include significant colon inflammation (colitis), liver problems, skin reactions, nerve and hormone gland inflammation, and eye problems. Patients are closely monitored for diarrhea, rashes, itching, and other side effects. Before treatment begins, be sure to talk with your health care team about potential side effects. Let your health care team know right away if you develop any new symptoms during treatment. It is also important to tell your health care team about all other medications you are taking, including over-the-counter drugs and dietary or herbal supplements, to avoid possible side effects from drug interactions with ipilimumab.

Ipilimumab and other CTLA-4 inhibitors continue to be studied in clinical trials. See the Latest Research section for more information.

Combining different immunotherapies

A combination of ipilimumab and nivolumab may be used for the treatment of unresectable stage III or stage IV melanoma. This combination is better than either drug alone in reducing the size of tumors and delaying growth of tumors, and 58% of people on this combination have their tumors shrink. However, combining these drugs causes far more side effects. The decision to give this combination therapy is often based on how fast the cancer is growing, where the cancer has spread, and the general health of the person. ASCO recommends giving this combination followed by nivolumab alone as an option to treat unresectable stage III or metastatic melanoma whether or not the melanoma has a BRAF mutation.

A combination of nivolumab and relatlimab, called Opdualag, may also be used to treat unresectable stage III or stage IV melanoma in people aged 12 and older. Relatlimab is an immune checkpoint inhibitor that targets lymphocyte-activation gene 3 (LAG-3).

Interleukin-2 (IL-2, Proleukin)

Interleukin-2 is a type of immunotherapy that activates T cells. It is sometimes given to people with metastatic melanoma. The number of people for whom this treatment works is similar to that of ipilimumab (about 16%), with fewer than 10% of people experiencing a complete response. A complete response is defined as the disappearance of all signs of cancer as a result of treatment.

This treatment often has multiple and significant side effects. The most common side effects of IL-2 are flu-like symptoms (fevers, chills, and aches), rash, and gastrointestinal side effects (nausea, vomiting, and diarrhea). IL-2 also causes capillary leak syndrome, which occurs when fluids and proteins leak from blood vessels. Capillary leak syndrome can cause very low blood pressure and other dangerous effects. The side effects of the drug can be very serious and even life-threatening for small number of people on IL-2. Patients treated with high-dose IL-2 require intensive monitoring by the health care team. IL-2 should be given by an experienced health care team familiar with the side effects of IL-2 treatment.

Virus therapy

Virus therapy, also called oncolytic viruses or intralesional therapy, is a type of immunotherapy that includes talimogene laherparepvec (T-VEC; Imlygic). T-VEC may be used to treat unresectable stage III and stage IV melanoma. T-VEC is a herpes virus designed in a laboratory to make an immune-stimulating hormone. This virus can infect and destroy melanoma cells. T-VEC also helps stimulate the immune system to destroy other melanoma tumors.

T-VEC is injected directly into 1 or more melanoma tumors, so it is also called intralesional therapy. Since T-VEC has not been shown to cause significant shrinkage of non-injected tumors in most people, patients with widely metastatic disease are not usually offered this treatment. T-VEC may be offered to patients with unresectable or metastatic melanoma who cannot or choose not to receive any other recommended treatments. T-VEC is being studied in combination with other medications to improve its effectiveness.

Interferon

Both high-dose interferon alfa-2b (Intron A) and pegylated interferon alfa-2b (Sylatron) have been shown to delay recurrence for some patients. However, neither of these treatments has been shown to lengthen how long most people live. There are substantial and common side effects with these treatments, including flu-like symptoms, such as fatigue, fever, chills, nausea, vomiting, and headache; rashes; hair thinning; and depression. Because of the side effects and because they are not proven to lengthen life for most patients who receive this treatment, ASCO does not recommend the routine use of interferon therapy in melanoma.

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Targeted therapy

Targeted therapy is a treatment that targets the cancer’s specific genes, proteins, or the tissue environment that contributes to cancer growth and survival. This type of treatment blocks the growth and spread of cancer cells and limits damage to healthy cells. Learn more about the basics of targeted treatments.

As explained here and in Diagnosis, ongoing research has identified several key pathways and genes involved in the growth and spread of melanoma. These advances have allowed doctors to tailor or personalize the treatment plan based on the melanoma’s genetic abnormalities or mutations.

A major focus in research is the development of new drugs that block specific biochemical pathways that melanoma cells need to grow.

BRAF inhibitors

The discovery that about 50% of melanomas have a mutated or activated BRAF gene has provided an important direction in targeted therapy for melanoma. BRAF inhibitors approved to treat unresectable stage III and stage IV melanoma include:

  • Dabrafenib (Tafinlar)

  • Encorafenib (Braftovi)

  • Vemurafenib (Zelboraf)

These drugs, taken as a pill, are specifically used when the melanoma tumors have a V600E or V600K mutation in the BRAF gene (see Diagnosis). These drugs should not be used by patients without the mutation because it can actually be harmful for them. The addition of a MEK inhibitor to BRAF inhibitors has been shown in multiple studies to increase tumor shrinkage rate as well as delay tumor growth (see below).

Vemurafenib may be given in combination with atezolizumab (see “PD-1 and PD-L1 inhibitors” above) and the MEK inhibitor cobimetinib to treat advanced melanoma with a BRAF V600 mutation.

Side effects of these medications depends on the medication. Common side effects of vemurafenib include skin problems (such as rashes), hair thinning, thick or dry skin, sun sensitivity, and a less aggressive form of skin cancer called squamous cell carcinoma that can often be treated with minor surgery. Other side effects included joint pain, fatigue, nausea, fever, and hair thinning and curling. Dabrafenib seems to have fewer side effects like thick or dry skin and hair thinning, and only rarely causes sun sensitivity.

Talk with your doctor about what side effects may occur before your specific treatment begins.

MEK inhibitors

Trametinib (Mekinist), cobimetinib (Cotellic), and binimetinib (Mektovi) are approved as a targeted therapy for unresectable or metastatic melanoma with a BRAF V600E or V600K mutation. These drugs, which are taken as a pill, specifically target the MEK protein, which is involved in cancer growth and survival. While trametinib originally was approved based on the results of a clinical study that showed people with stage IIIC or stage IV melanoma who took this targeted therapy lived longer without the cancer getting worse than those who received chemotherapy, these medications (trametinib, cobimetinib, and binimetinib) are almost always given in combination with a BRAF inhibitor. These combinations are described in more detail below. 

Cobimetinib may also be given in combination with atezolizumab (see “PD-1 and PD-L1 inhibitors,” above) and the BRAF inhibitor vemurafenib to treat advanced melanoma with a BRAF V600 mutation. 

Combining BRAF and MEK inhibitors

Clinical trials have shown that there are improved outcomes and reduced side effects when a BRAF and MEK inhibitor are combined compared with giving a BRAF or MEK inhibitor alone. It has become standard practice to recommend 1 of the 3 following approved combinations when targeted therapy is being offered to patients with tumors that have BRAF mutations.

ASCO recommends dabrafenib plus trametinib as an option to treat stage III melanoma with a BRAF mutation after surgery. For unresectable or metastatic melanoma with a BRAF mutation, ASCO recommends dabrafenib plus trametinib, encorafenib plus binimetinib, or vemurafenib plus cobimetinib as options.

Dabrafenib and trametinib. There have been 2 clinical trials showing that the combination of dabrafenib, a BRAF inhibitor, and trametinib, a MEK inhibitor, is associated with better tumor shrinkage rates, delay in tumor growth, and longer life compared to vemurafenib alone, in 1 study, and dabrafenib alone, in the other study. As a result of these trials, the FDA approved the combination of dabrafenib with trametinib for the treatment of unresectable advanced melanoma and metastatic melanoma with a BRAF V600E or V600K mutation. This combination is not expected to help people who have melanoma that does not have a detectable BRAF mutation.

In a more recent clinical trial, 1 year of treatment with the combination of dabrafenib and trametinib was shown to improve outcomes in people with stage III melanoma after the completion of surgery. This data led to the approval of this combination, in 2018, as an adjuvant therapy for people with stage III melanoma that has been removed by surgery.

The most common side effects of this combination include fever, chills, tiredness, rash, nausea, vomiting, diarrhea, abdominal pain, swelling in the hands and feet, cough, headache, joint pain, night sweats, decreased appetite, constipation, and muscle pain. The combination of dabrafenib and trametinib reduces some side effects when compared to either of the medicines taken separately, including a lower rate of secondary skin cancers and rash.

Vemurafenib and cobimetinib. In 2015, the FDA approved the combination of vemurafenib and cobimetinib. A clinical trial has shown that the combination of vemurafenib and cobimetinib is associated with better tumor shrinkage rates, delay in tumor growth, and longer life compared to vemurafenib alone. The common side effects with this combination include tiredness, nausea, diarrhea, joint aches, sun sensitivity, rash, fever, liver irritation, and swelling in the hands and feet.

Encorafenib and binimetinib. In 2018, the FDA approved the combination of encorafenib and binimetinib. A phase III clinical trial showed that this combination helped people live longer than those treated with vemurafenib alone. The most common side effects of this combination were fatigue, nausea, diarrhea, vomiting, abdominal pain, and joint pain.

KIT inhibitors

Researchers are also focusing on the development of targeted therapies for the KIT gene, which is mutated or present in increased numbers (extra copies of the gene) in some tumors in certain subtypes of melanoma, including lentigo maligna melanoma, mucosal melanoma, and acral lentiginous melanoma. Drugs currently being tested in clinical trials for people with stage IV, mutated KIT melanoma include dasatinib (Sprycel), imatinib (Gleevec), and nilotinib (Tasigna).

Tumor-agnostic treatment

Larotrectinib (Vitrakvi) and entrectinib (Rozlytrek) are targeted therapies that are not specific to a certain type of cancer but instead focus on a specific genetic change called an NTRK fusion. This type of genetic change is found in a range of cancers, including melanoma. These medications are approved for the treatment of unresectable or metastatic melanoma with an NTRK fusion that has worsened with other treatments.

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Chemotherapy

Chemotherapy is the use of drugs to destroy cancer cells, usually by keeping the cancer cells from growing, dividing, and making more cells.

Because immunotherapy and targeted therapy have become more effective at treating melanoma, chemotherapy is used much less often.

A chemotherapy regimen, or schedule, usually consists of a set number of cycles given over a specific time. A patient may receive 1 drug at a time or a combination of different drugs given at the same time. Dacarbazine (DTIC; available as a generic drug) is the only FDA-approved chemotherapy for melanoma. Temozolomide (Temodar) is essentially an oral version of dacarbazine, and it is used for the treatment of stage IV melanoma.

Both DTIC and temozolomide have been shown to shrink melanoma for about 12% to 15% of patients. However, no clinical trials have tested whether these drugs help people with melanoma live longer after treatment. Both drugs have a limited number of side effects. Talk with your doctor about possible side effects of these drugs.

Other chemotherapies that may be used to treat melanoma include a generic drug called cisplatin, fotemustine (Muphoran, which is only approved in Europe), lomustine (Gleostine), the taxanes (a group of drugs that includes docetaxel [Taxotere] and paclitaxel [Taxol]), and another generic drug called vinblastine. Combinations of chemotherapy drugs may be used, such as paclitaxel plus carboplatin or cisplatin combined with vinblastine and dacarbazine. Some chemotherapy combinations may have a higher chance of causing melanoma to shrink, but they also cause more side effects.

The side effects of chemotherapy depend on the individual and the dose used, but they can include fatigue, risk of infection, nausea and vomiting, nail changes, loss of appetite, diarrhea, some nerve damage causing changes in sensation, and hair loss. These side effects usually go away after treatment is finished.

Learn more about the basics of chemotherapy.

Isolated limb infusion therapy

Sometimes, melanoma may spread and appear as a number of tumors that develop in the leg or arm. In these situations, there are too many tumors for surgery to be possible or helpful. Depending on the overall extent and pattern of spread of the tumors, a doctor may recommend isolated limb infusion or perfusion with chemotherapy.

During this treatment, a tourniquet is placed on the arm or leg before high doses of chemotherapy are given. In isolated limb infusion, the interventional radiology team places a catheter to deliver the chemotherapy. In isolated limb perfusion, thin tubes called cannulae are placed surgically to deliver the chemotherapy. The tourniquet keeps the chemotherapy in the arm or leg and prevents it from being transported throughout the body. This therapy typically is administered with general anesthesia in the operation room.

Around 50% to 80% of tumors located in the area where the chemotherapy is circulated shrink as a result of this treatment. While tumor shrinkage is usually temporary, melanoma may be controlled for a year or more in some people. Researchers are also testing the effectiveness of combining isolated limb infusion therapy with other medicine.

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Physical, emotional, and social effects of cancer

Melanoma and its treatment cause physical symptoms and side effects, as well as emotional, social, and financial effects. Managing all of these effects is called palliative care or supportive care. It is an important part of your care that is included along with treatments intended to slow, stop, or eliminate the cancer.

Palliative care focuses on improving how you feel during treatment by managing symptoms and supporting patients and their families with other, non-medical needs. Any person, regardless of age or type and stage of cancer, may receive this type of care. And it often works best when it is started right after a cancer diagnosis. People who receive palliative care along with treatment for the cancer often have less severe symptoms, better quality of life, and report that they are more satisfied with treatment.

Palliative treatments vary widely and often include medication, nutritional changes, relaxation techniques, emotional and spiritual support, and other therapies. You may also receive palliative treatments similar to those meant to get rid of the cancer, such as medications, surgery, or radiation therapy.

Before treatment begins, talk with your doctor about the goals of each treatment in the recommended treatment plan. You should also talk about the possible side effects of the specific treatment plan and palliative care options. Many patients also benefit from talking with a social worker and participating in support groups. Ask your doctor about these resources, too.

During treatment, your health care team may ask you to answer questions about your symptoms and side effects and to describe each problem. Be sure to tell the health care team if you are experiencing a problem. This helps the health care team treat any symptoms and side effects as quickly as possible. It can also help prevent more serious problems in the future.

Learn more about the importance of tracking side effects in another part of this guide. Learn more about palliative care in a separate section of this website.

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Treatment by stage of melanoma

Different treatments may be recommended for each stage of melanoma. The general options by stage are described below. For more detailed descriptions, see “How melanoma is treated,” above. Your doctor will work with you to develop a specific treatment plan based on your specific diagnosis and needs. Clinical trials may also be a treatment option for each stage.

Stage 0 melanoma

Stage 0 melanoma is almost always treated with surgery alone, usually a wide excision.

Stage I melanoma

Stage I melanoma is usually treated with surgical removal of the tumor and some of the healthy tissue around it. The doctor may recommend lymph node mapping, and some lymph nodes may be removed.

Stage II melanoma

The standard treatment for stage II melanoma is surgery to remove the tumor and some of the healthy tissue around it. While this surgery is being done, lymphatic mapping and sentinel lymph node biopsy may also be done. For people with stage IIB and stage IIC melanoma, discuss with your medical oncologist whether treatment with 1 year of pembrolizumab is an option for you. Treatment in a clinical trial for stage II melanoma may also be an option. Ask your doctor about what clinical trials may be available for you.

Stage III melanoma that can be removed with surgery

Stage III melanoma has spread locally or through the lymphatic system to a regional lymph node or to a skin site on the way to a lymph node. If the stage III melanoma can be removed with surgery, this typically will be the first treatment option. The lymph nodes may be checked for cancer and removed. After surgery, treatment with immunotherapy or targeted therapy may be recommended to help prevent the cancer from coming back.  Treatment in a clinical trial for stage III melanoma may also be an option. Ask your doctor about what clinical trials may be available for you. Some of these research studies may involve treatment with systemic medication before surgery, called neoadjuvant therapy. This is not a standard treatment, but there is emerging data from clinical trials that this may be an effective approach for certain patients.

Advanced melanoma

Advanced melanoma is a stage III melanoma that cannot be treated with surgery or stage IV melanoma. Stage IV melanoma has spread to distant parts of the body, such as distant lymph nodes or the liver, lung, brain, bone, or gastrointestinal tract. Doctors may refer to this as metastatic melanoma. If this happens, it is a good idea to talk with doctors who have experience treating it. Doctors can have different opinions about the best standard treatment plan. Clinical trials might also be an option. Learn more about getting a second opinion before starting treatment, so you are comfortable with your chosen treatment plan.

Unresectable stage III melanoma and stage IV melanoma are often treated the same way, with immunotherapy and targeted therapy, or, in rare cases, chemotherapy. Palliative or supportive treatments intended to relieve symptoms may also be recommended, such as surgery or radiation therapy to treat affected lymph nodes and tumors that have spread elsewhere in the body. Finally, surgery may be recommended to remove 1 or 2 tumors if there are few sites of disease. The treatment plan will also depend on a number of factors:

  • The person’s age and overall health

  • The locations and number of metastases

  • How fast the disease is spreading

  • The presence of specific genetic mutations in the tumor

  • The patient’s preferences and goals of care

  • How treatment is to be given and how that affects the patient's quality of life

If the recommended treatment does not work, stops working, or causes serious side effects, your doctor may suggest changing the treatment plan.

For many people, a diagnosis of advanced cancer is very stressful and difficult. You and your family are encouraged to talk about how you feel with doctors, nurses, social workers, or other members of your health care team. It may also be helpful to talk with other patients, such as through a support group or other peer support program.

Surgery to remove metastatic tumors

There are times when it may be appropriate to remove one or more metastatic tumors (a surgery called metastatectomy) in people with stage IV melanoma. While the development of more effective therapies has reduced the use of surgery to be the main treatment for metastatic melanoma, surgery may be used to remove 1 or more tumors that are causing symptoms or tumors that are growing while a person is receiving systemic therapy. This is most commonly done when other tumors have shrunk or gone away or if there are only a few tumors in the body.

Treating brain metastases

The brain is one of the most common places to which melanoma spreads. Unfortunately, the presence of brain metastases is linked with a poor prognosis. Prognosis is the chance of recovery. Traditionally, less than 50% of people with melanoma that has spread to the brain live 6 months, although this has changed in recent years. Because of this poor prognosis and because of the perceived difficulty in getting cancer medications into brain tissue (called the blood-brain barrier), people with melanoma that has spread to the brain have typically not been allowed into clinical trials. Fortunately, this is changing, and there are recently completed and ongoing clinical trials for patients with melanoma and brain metastases. Read this fact sheet to learn more about cancer that has spread to the brain.

Currently, the following treatments may be recommended for melanoma that has spread to the brain:

  • Radiation therapy. High-dose radiation therapy given using stereotactic techniques (see "Radiation therapy," above) is often used when there are only a few metastatic tumors in the brain. These techniques are highly effective for getting rid of existing tumors. However, they do not prevent new tumors from developing. The entire brain can be treated with radiation therapy, called whole-brain radiation therapy. However, because the dose of radiation used to treat the entire brain is lower, this type of treatment usually does not shrink tumors and commonly causes problems with thinking clearly (cognition).

  • BRAF and MEK inhibitors. For people with melanoma that has a BRAF mutation, combinations of a BRAF and a MEK inhibitor may be recommended. These drugs penetrate into the brain metastases. Clinical trials have shown that melanoma tumors in the brain treated with these medications shrink around 40% to 50% of the time. For those with a BRAF V600E mutation, with or without symptoms from the brain metastases, the doctor may recommend treatment with a combination of a BRAF and a MEK inhibitor.

  • Immunotherapy. Ipilimumab, nivolumab, and pembrolizumab have recently been studied in clinical trials to treat people with melanoma that has spread to the brain. These studies have shown that these treatments can help patients with melanoma and brain metastases. For those with no symptoms from the brain metastases, with or without a BRAF mutation, the doctor may recommend treatment with ipilimumab plus nivolumab. Although this combination of ipilimumab and nivolumab appears to be an effective treatment, it has a high rate of side effects and may not be the right choice for everybody.

  • Surgery. Surgery may be offered to some people to remove tumors in the brain, especially if they are causing symptoms.

Below is a general summary of when and how surgery and radiation therapy are used to treat brain metastases:

  • People with 1 to 3 brain metastases generally receive stereotactic radiosurgery. If the brain metastases are large or causing symptoms due pressure on the brain and the person is in general good health, they often receive surgery, followed by stereotactic radiosurgery.

  • Treatment for people in relatively good health and with more than 4 tumors that cannot be removed with surgery or more than 2 tumors that were removed surgically may include stereotactic radiosurgery or whole brain radiation therapy.

  • People who also have metastatic cancer in parts of the body other than the brain usually continue their treatment regimen if the disease outside the brain is not worsening. If the disease is worsening, the treatment plan may be changed based on the recommendations for that type of metastatic cancer.

The information in this section is based on a joint guideline from ASCO, the Society for Neuro-Oncology (SNO), and the American Society for Radiation Oncology (ASTRO), “Treatment for Brain Metastases.” Please note that this link takes you to a different ASCO website.

Learn about caring for someone with cancer that has spread to the brain.

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Remission and the chance of recurrence

A remission is when cancer cannot be detected in the body and there are no symptoms. This may also be called having “no evidence of disease” or NED.

A remission may be temporary or permanent. This uncertainty causes many people to worry that the cancer will come back. While many remissions are permanent, it is important to talk with your doctor about the possibility of the cancer returning. Understanding your risk of recurrence and the treatment options may help you feel more prepared if the cancer does return. Learn more about coping with the fear of recurrence.

If the melanoma returns after the original treatment, it is called recurrent cancer. It may come back in the same place (called a local recurrence), nearby (regional recurrence), or in another part of the body (distant recurrence).

If a recurrence happens, a new cycle of testing will begin to learn as much as possible about it. After this testing is done, you and your doctor will talk about the treatment options. Often the treatment plan will include the treatments described above, such as surgery, chemotherapy, immunotherapy, targeted therapy, and radiation therapy, but they may be used in a different combination or given at a different pace. Your doctor may suggest clinical trials that are studying new ways to treat recurrent melanoma. Whichever treatment plan you choose, palliative care will be important for relieving symptoms and side effects.

People with recurrent cancer sometimes experience emotions such as disbelief or fear. You are encouraged to talk with your health care team about these feelings and ask about support services to help you cope. Learn more about dealing with cancer recurrence.

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If treatment does not work

Recovery from melanoma is not always possible. If the cancer cannot be cured or controlled, the disease may be called advanced or terminal.

This diagnosis is stressful, and for some people, advanced cancer is difficult to discuss. However, it is important to have open and honest conversations with your health care team to express your feelings, preferences, and concerns. The health care team has special skills, experience, and knowledge to support patients and their families and is there to help. Making sure a person is physically comfortable, free from pain, and emotionally supported is extremely important.

People who have advanced cancer and who are expected to live less than 6 months may want to consider hospice care. Hospice care is designed to provide the best possible quality of life for people who are near the end of life. You and your family are encouraged to talk with the health care team about hospice care options, which include hospice care at home, a special hospice center, or other health care locations. Nursing care and special equipment can make staying at home a workable option for many families. Learn more about advanced cancer care planning.

After the death of a loved one, many people need support to help them cope with the loss. Learn more about grief and loss.

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The next section in this guide is About Clinical Trials. It offers more information about research studies that are focused on finding better ways to care for people with cancer. Use the menu to choose a different section to read in this guide.