Melanoma. Treatment Guidelines for Patients

Transcription

1 Melanoma Treatment Guidelines for Patients Version III/ September 2005

2 Current ACS/NCCN Treatment Guidelines for Patients Advanced Cancer and Palliative Care Treatment Guidelines for Patients (also in Spanish) Bladder Cancer Treatment Guidelines for Patients (also in Spanish) Breast Cancer Treatment Guidelines for Patients (also in Spanish) Cancer Pain Treatment Guidelines for Patients (also in Spanish) Cancer-Related Fatigue and Anemia Treatment Guidelines for Patients (also in Spanish) Colon and Rectal Cancer Treatment Guidelines for Patients (also in Spanish) Distress Treatment Guideline for Patients (also in Spanish) Fever and Neutropenia Treatment Guidelines for Patients with Cancer (also in Spanish) Lung Cancer Treatment Guidelines for Patients (also in Spanish) Melanoma Cancer Treatment Guidelines for Patients (also in Spanish) Nausea and Vomiting Treatment Guidelines for Patients with Cancer (also in Spanish) Non-Hodgkin s Lymphoma Treatment Guidelines for Patients (also in Spanish) Ovarian Cancer Treatment Guidelines for Patients (also in Spanish) Prostate Cancer Treatment Guidelines for Patients (also in Spanish)

3 Melanoma Treatment Guidelines for Patients Version III/ September 2005 The mutual goal of the National Comprehensive Cancer Network (NCCN) and the American Cancer Society (ACS) partnership is to provide patients and the general public with state-of-the-art cancer treatment information in an easy-tounderstand language. This information, based on the NCCN s Clinical Practice Guidelines, is intended to assist you in a discussion with your doctor. These guidelines do not replace the expertise and clinical judgment of your doctor.

4 NCCN Clinical Practice Guidelines were developed by a diverse panel of experts. The guidelines are a statement of consensus of its authors regarding the scientific evidence and their views of currently accepted approaches to treatment. The NCCN guidelines are updated as new, significant data become available. The Patient Information version will be updated accordingly and will be available on-line through the NCCN and the ACS Web sites. To ensure that you have the most up-to-date version of the guidelines, consult the Web sites of the ACS ( or NCCN ( You may also call the NCCN at NCCN or the ACS at ACS-2345 for the most recent information by the National Comprehensive Cancer Network (NCCN) and the American Cancer Society (ACS). All rights reserved. The information herein may not be reprinted in any form for commercial purposes without the express written permission of the ACS and NCCN. Single copies of each page may be reproduced for personal and noncommercial uses by the reader.

5 Contents Introduction Making Decisions About Melanoma Treatment About the Skin Types of Skin Cancer Tests and Exams for Melanoma Work-up (Diagnosis and Evaluation) Melanoma Stages Types of Treatment for Melanoma Complementary and Alternative Therapies About Clinical Trials Other Things to Consider During and After Treatment Protecting Your Skin From Sun Exposure Checking Your Skin Work-up (Evaluation) and Treatment Guidelines Decision Trees Work-up for Melanoma Work-up and Treatment for Lower Stages of Melanoma Work-up and Treatment for Higher Stages of Melanoma Follow-up After Initial Treatment of Melanoma Treatment If the Cancer Comes Back (Recurrence) Treatment of Melanoma That Presents or Recurs With Distant Spread Glossary

6 Member Institutions Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at The Ohio State University City of Hope Cancer Center Dana-Farber/Partners CancerCare Duke Comprehensive Cancer Center Fox Chase Cancer Center Fred Hutchinson Cancer Research Center/ Seattle Cancer Care Alliance H. Lee Moffitt Cancer Center & Research Institute at the University of South Florida Huntsman Cancer Institute at the University of Utah Memorial Sloan-Kettering Cancer Center Robert H. Lurie Comprehensive Cancer Center of Northwestern University Roswell Park Cancer Institute St. Jude Children s Research Hospital/ University of Tennessee Cancer Institute Stanford Hospital and Clinics The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins UCSF Comprehensive Cancer Center University of Alabama at Birmingham Comprehensive Cancer Center University of Michigan Comprehensive Cancer Center The University of Texas M. D. Anderson Cancer Center UNMC/Eppley Cancer Center at The Nebraska Medical Center

7 Introduction With this booklet, patients have information on the way melanoma is treated at the nation s leading cancer centers. Originally developed for cancer specialists by the National Comprehensive Cancer Network (NCCN), these treatment guidelines have now been written for the general public by the American Cancer Society (ACS). To obtain another copy of these guidelines, call the ACS at ACS-2345, or the NCCN at NCCN, or visit these organizations Web sites at (ACS) and (NCCN). These patient guidelines will help you better understand your cancer treatment options. We urge you to discuss them with your doctor. You might start by asking the following questions: Where is my cancer located? How far has my cancer spread? What is the stage of my cancer? How does this stage influence my outlook for cure and survival and my treatment options? What treatment options do I have? What are the risks or side effects associated with each of my treatment options, and how are they likely to affect my quality of life? What should I do to be ready for treatment, reduce side effects of treatment, and hasten my recovery? What clinical trials are available for me? In addition to these questions, be sure to write down some of your own. For instance, you might want more information about how long it will take you to recover from surgery so you can plan your work schedule. Or you may want to ask about clinical trials. Making Decisions About Melanoma Treatment The American Cancer Society estimates that around 60,000 new melanomas will be diagnosed in the United States each year. The number of new melanomas diagnosed in the US is increasing. Since 1973, the incidence rate for melanoma (the number of new melanomas diagnosed per 100,000 people each year) has more than doubled. About 7,800 people in the US are expected to die of melanoma in Since 1973, the mortality rate for melanoma (the number of deaths from melanoma per 100,000 people each year) has increased. The good news is that melanoma mortality rates have only slightly increased during the past 10 years. Although melanoma is a serious disease, it can be treated and cured. It is important that you receive care from a team of health care professionals who are experienced in treating melanoma. This team may include a dermatologist, a surgeon, medical oncologist, radiation oncologist, pathologist, nurse, radiologist, and social worker often along with your primary care doctor. The information in this booklet is intended to help you understand your options for treatment of melanoma so that you and your cancer care team can work together to decide which treatment is best for you. At the end of this discussion, you ll find flowcharts that doctors call decision trees. The charts represent different stages of 5

8 melanoma, and each one shows how you and your doctor can arrive at the choices you need to make about your treatment. To reach an informed decision, you need to understand some of the medical terms that your doctors use. You may feel you re on familiar ground already, or perhaps you need to refer to the various sections listed on the front-page index. You will find not only background information on melanoma, but also explanations of melanoma stages, work-up (evaluation), and treatments all categories used in the flowcharts. We ve also provided a glossary of medical terms that can be found at the end of this booklet. The terms in italics are included in the glossary. About the Skin The skin has 3 layers called the epidermis, dermis, and subcutis. The top layer is the epidermis. The epidermis is very thin, averaging only 0.2 mm (about of an inch). It protects the deeper layers of skin and the organs of the body from the environment. The outermost part of the epidermis is called the stratum corneum, or horny layer. It is composed of dead cells of the epidermis that are continually shed. Below the stratum corneum are layers of living cells called squamous cells. These cells form an important protein called keratin. Keratin contributes to the skin s ability to protect the rest of the body. The lowest part of the epidermis, the basal layer, is formed by basal cells. These cells continually divide to form new cells to replace the older ones that wear off the skin s surface. Melanoma comes from cells called melanocytes that are also present in the epidermis. These skin cells produce the protective pigment called melanin. Melanin gives a tan or brown color to the skin and helps protect the deeper layers of the skin from the harmful effects of the sun. The basal lamina separates the epidermis from the deeper layers of skin. Squamous cell Epidermis Epidermis Dermis Melanocyte Basal cell Sweat gland Subcutis Blood vessel Sweat gland Hair follicle Lymph vessel 6

9 The middle layer of the skin is called the dermis. The dermis is much thicker than the epidermis. It contains hair follicles, sweat glands, blood vessels, and nerves that are held in place by a protein called collagen. Collagen, which is made by skin cells called fibroblasts, gives the skin its resilience and strength. Below the skin is the subcutis. The subcutis and the lowest part of the dermis form a network of collagen and fat cells. The subcutis conserves heat and has a shock-absorbing effect that helps protect the body s organs from injury. Types of Skin Cancer Skin cancers are divided into 2 general types: melanoma and nonmelanoma. Nonmelanoma skin cancers (usually basal cell and squamous cell skin cancers) are the most common cancers of the skin. They are called nonmelanoma skin cancer because they develop from skin cells other than melanocytes. Because they rarely spread elsewhere in the body, they are treated differently. Melanoma is a cancer that begins in the melanocytes, the cells that produce the skin coloring or pigment known as melanin. Because most melanoma cells still produce melanin, melanoma tumors are often brown or black. Although melanoma is much less common than basal cell and squamous cell cancers, it can be more dangerous. Melanoma, like basal cell and squamous cell cancers, is almost always curable in its early stages. However, melanoma is much more likely than basal or squamous cell cancer to spread to other parts of the body. Melanomas can occur anywhere on the skin, but are more likely to develop in certain locations. The trunk is the more common site in men. In women, the legs are more commonly affected. Having darkly pigmented skin lowers the risk of being diagnosed with melanoma, but it is not a guarantee that you will not develop melanoma. Anyone, including people with dark skin, can develop this cancer on the palms of the hands, soles of the feet, and under the nails. Melanomas of the palms, soles, and nails represent about half of all melanomas in African Americans but fewer than 10% of melanomas in whites. Tests and Exams for Melanoma Work-up (Diagnosis and Evaluation) How Is Melanoma Diagnosed? A new lesion, or spot, or growth on your skin raises the possibility of melanoma. Your doctor will do an examination and other various tests will be used to find out whether it is melanoma, nonmelanoma, or some other skin condition. A specific diagnosis can only be made by doing a skin biopsy. History and Physical Examination Usually the first step is for your doctor to take your medical history (questions about symptoms and risk factors). The doctor will ask when the skin lesion first appeared and whether it has changed in size or appearance. You may also be asked about past exposures to known causes of melanoma and whether anyone in your family has had melanoma. 7

10 During the physical examination, your doctor will note the size, shape, color, and texture of the area in question and look for any bleeding or scaling. The rest of your body will be checked for spots and moles that may be related to melanoma. The doctor will also examine lymph nodes in areas near the abnormal area of skin. Lymph nodes, also called lymph glands, are small bean-shaped collections of immune system tissue that are found along lymphatic vessels. Enlarged lymph nodes might suggest the spread of a melanoma to these structures. Seeing a Specialist If your doctor is not a specialist in skin disorders (dermatologist), you may be sent to one for further evaluation and a biopsy. Types of Skin Biopsy If the doctor thinks a melanoma might be present, he or she will take a sample of skin from the suspicious area for examination under a microscope. This is called a skin biopsy. Different methods can be used. The choice depends on the size of the affected area and its location on your body. Any biopsy is likely to leave a scar. Because different methods produce different types of scars, you should ask the doctor about biopsies and scarring before the procedure is done. Skin biopsies are done using a local anesthetic. You will typically feel a small needle stick and a little burning with some pressure for less than a minute. All skin biopsy samples are examined under a microscope. The skin sample is sent to a pathologist, a doctor who has been specially trained in the microscopic examination and diagnosis of tissue samples. Often, the skin sample is sent to a dermatopathologist, a dermatologist, or pathologist who has additional training in making diagnoses from skin samples and may be more experienced with certain skin cancers than a general pathologist. He or she will determine if the cells appear dysplastic, that is, abnormal or may become cancerous. Incisional and excisional biopsies An incisional biopsy removes only a portion of the tumor. Removal of the entire tumor is called an excisional biopsy. A small piece of skin is removed for further examination, and the edges of the wound are sewn together. Both types of biopsies can be done using local anesthesia. Excisional biopsy is the method usually preferred when melanoma is suspected. Only a narrow rim of normal skin should be taken with this biopsy. Punch biopsy A punch biopsy removes a small sample of skin. The doctor uses a punch biopsy tool that looks like a tiny, round cookie cutter. Once the skin is numbed with a local anesthetic, the doctor rotates the punch biopsy tool on the surface of the skin until it cuts through all the layers of the skin, including the epidermis, dermis, and the upper parts of the subcutis. It may be appropriate for areas such as the palm, sole, digit, face ear, or for very large lesions. Shave biopsy After numbing the area with a local anesthetic, the doctor shaves off the top layers of the skin (the epidermis and part of the dermis) with a surgical blade. A shave biopsy is useful in diagnosing many types of skin diseases 8

11 and in treating benign (noncancerous) moles. However, if an invasive melanoma is suspected, a shave biopsy sample may not be deep enough to precisely measure its thickness or depth of invasion. If melanoma is suspected, a shave biopsy is usually not done. Blood Tests There are no specific blood tests for melanoma, but sometimes a blood LDH level might be helpful. LDH (lactate dehydrogenase) is an enzyme found in the blood that may be elevated when a lot of cancer cells are present or when the liver has been damaged by cancer. Blood LDH levels can be a marker for widespread melanoma. It is seldom elevated at the time of initial diagnosis. Imaging Studies Chest x-ray A chest x-ray may be taken to determine whether the melanoma has spread (metastasized) to the lungs. A chest x-ray is sometimes not needed for patients with very early (thin) melanoma. Imaging methods such as computed tomography (CT) scans, magnetic resonance imaging (MRI) scans, and positron emission tomography (PET) may be used to see whether the melanoma has spread to other organs or to lymph nodes deep inside the body. These tests may not always be needed and are used mostly for patient with known or suspected metastases. Computed tomography (CT) The CT scan is an x-ray procedure that produces detailed cross-sectional images of your body. Instead of taking one picture, as does a usual chest x-ray, a CT scanner takes many pictures as it rotates around you. A computer then combines these pictures into an image of a slice of your body. The machine produces multiple images of the part of your body that is being studied. Often after the first set of pictures is taken, you will receive an intravenous injection of a special dye that helps better outline structures in your body. A second set of pictures is then taken. Some people get hives or, rarely, more serious allergic reactions like trouble breathing and low blood pressure can occur. Be sure to tell the doctor if you have ever had a reaction to any contrast material used for x-rays. The CT may detect melanoma if it has spread to your lungs or liver and can help find enlarged lymph nodes that might contain cancer. Magnetic resonance imaging (MRI): MRI scans use radio waves and strong magnets instead of x-rays. The energy from the radio waves is absorbed and then released in a pattern formed by the type of tissue and by certain diseases. A computer translates the pattern of radio waves given off by the tissues into very detailed cross-sectional images of parts of the body. A contrast material might be injected just as with CT scans. MRI can be very useful for looking for tumors in the brain and spinal cord. Positron emission tomography: Positron emission tomography (PET) uses glucose (a form of sugar) that contains a radioactive atom. Cancer cells of the body absorb large amounts of the radioactive sugar because of their high rate of metabolism. The substance 9

12 is injected into a vein, and a special camera can detect the radioactivity in the body. PET may supplement the results of the CT and MRI examinations. Note: In general, all these scans with radioactive compounds are easy to take. There are usually no side effects, and you are exposed to only a tiny amount of radioactive substance. Procedures and Tests to Detect Metastases Sentinel lymph node mapping and biopsy: This has become a standard procedure for finding the lymph nodes that drain lymph fluid from the area of the skin where the melanoma developed. If the melanoma has spread, these lymph nodes are usually the first place it will go. That is why these lymph nodes are called sentinel nodes (sentinel means to watch over the tumor, so to speak). These lymph nodes are then checked by a pathologist for any spread of melanoma. It is done to help determine a patient s risk of recurrence and to help guide treatment decisions. To map the sentinel lymph node, some time before surgery the doctor injects a small amount of radioactive material into the melanoma. By checking various lymph node areas with a radioactivity detection device like a Geiger counter, the doctor can see what group of lymph nodes your melanoma is most likely to travel to in order to find the sentinel lymph node. Then the doctor injects a small amount of a harmless blue dye and radioactive chemical into the site of the melanoma. After about an hour, a surgeon makes a small incision in the identified lymph node area. The lymph nodes can then be checked to find which one has turned blue or become radioactive. When the appropriate sentinel node has been found, it will be removed for microscopic examination. If melanoma cells are found in this lymph node, the remaining lymph nodes in this area are surgically removed. If the sentinel node does not contain melanoma cells, no more lymph node surgery is needed. If a lymph node near a melanoma is abnormally large, an FNA or surgical biopsy of that lymph node is done and the sentinel node procedure may not be needed. Fine needle aspiration biopsy A fine needle aspiration (FNA) biopsy uses a syringe with a very thin needle to remove cells from a mass. A local anesthetic is sometimes used to numb the area. This test rarely causes much discomfort and does not leave a scar. FNA may be used to biopsy enlarged lymph nodes near a melanoma to find out if the cancer has metastasized (spread). Sometimes the doctor can view a CT scan (a special type of x-ray) or ultrasound to guide the needle into a mass. Surgical (excisional) lymph node biopsy: In this procedure, an abnormally large lymph node is removed surgically through a small skin incision. Local anesthetic is generally used. This technique is often done if a lymph node s size suggests spread of melanoma, but the FNA did not find any melanoma cells. Diagnosis of Metastatic Melanoma Although many melanomas are completely cured, some melanomas spread so quickly that a patient can have spread of melanoma to the 10

13 lymph nodes, lungs, brain, gastrointestinal tract, or liver while the original melanoma is still small. On the other hand, melanoma that has spread to other parts of the body may not be found until long after the original melanoma was removed from the skin. When such spread has occurred, the metastatic melanoma in certain organs might be confused with a cancer starting in that organ. For example, melanoma that has spread to the lungs might be confused with a primary lung cancer (cancer that starts in the lungs). Special tests can be done on biopsy samples to tell whether it is a melanoma or some other kind of cancer. This is important because different cancers are treated differently. Examination of the Skin Biopsy It is important to measure the thickness of a melanoma under a microscope because this is believed to be one of the best ways to determine the prognosis (or outlook for survival). The pathologist examining the skin biopsy specimen measures the thickness of the melanoma under the microscope with a device called a micrometer, which is like a small ruler. This technique is called the Breslow measurement. The thinner the melanoma, the better the prognosis. In general, melanomas less than 1 millimeter (mm) in depth (about 1 25 of an inch or the diameter of a period or a comma) have a very small chance of spreading. As the melanoma becomes thicker, it has a greater chance of spreading. The thickness of the melanoma also guides the choice of treatment. Another system describes the thickness of a melanoma in relation to its penetration into the skin instead of actually measuring it. The Clark level of a melanoma uses a scale of I to V to describe thickness (with higher numbers indicating a deeper melanoma): (The Clark level Roman numerals should not be confused with the stage grouping Roman numerals.) if the melanoma stays in the epidermis (Clark level I) if the melanoma has begun to penetrate to the upper dermis (Clark level II) if the melanoma involves most of the upper dermis (Clark level III) if the melanoma has penetrated to the lower dermis (Clark level IV) if the melanoma has penetrated very deeply, to the subcutis (Clark level V) In the newest classification, the Breslow measurement of thickness has become more important than the Clark level of penetration as the first prognostic factor. This is because the thickness measurement is easier and depends less on the pathologist s judgment. Sometimes, however, the Clark level tells us that a melanoma is more advanced than we may think it is from the Breslow measurement. Therefore, both systems are often used to help stage a melanoma. In either system, the melanoma has a worse prognosis if the pathologist says it is ulcerated (covering layer of epidermis is absent). Melanoma Stages Staging is a process of describing how far a cancer has spread. This includes describing the size of the skin tumor and whether it has spread to any other organs. A staging system is a standard way for your health care team to summarize the extent of your cancer. 11

14 The American Joint Committee on Cancer (AJCC) staging system is used most often to describe the extent of melanoma. In this system, each cancer is given a T category, an N category, and an M category. The T category is based on the tumor s thickness and whether it is ulcerated (the layer of skin covering the melanoma is absent). The N category reflects whether the melanoma has spread to lymph nodes (small bean-shaped collections of immune system cells that help the body fight infections and cancers) near the melanoma. The N category also reflects whether the melanoma cancer cells are beginning to spread and are found in lymphatic channels connecting to the lymph nodes. The M category indicates whether there is spread (metastases) to distant organs. In TNM staging, information about the tumor, lymph nodes, and metastasis is combined according to a process called stage grouping to assign a stage. The stage is described using 0 and Roman numerals from I to IV. Several tests and procedures are used to gather information about a melanoma and whether it has spread to lymph nodes and distant organs. This information is used to assign T, N, and M categories and a grouped stage. Descriptions of Grouped Stages The stages used in these guidelines are as follows: Stage 0: The melanoma is in situ, meaning that it involves the epidermis but has not spread to the dermis. This is also called Clark level I. Stage IA: The melanoma is less than or equal to 1.0 mm or about 1 25 inch in thickness and no ulceration is present. Using the Clark system, this can be level II or III. It appears to be localized in the skin and has not been found in lymph nodes or distant organs. Stage IB: The melanoma is less than or equal to 1.0 mm in thickness and is ulcerated, or Clark IV or V, or it is between 1.01 and 2.0 mm and is not ulcerated. It appears to be localized in the skin and has not been found in lymph nodes or distant organs. Stage IIA: The melanoma is between 1.01 mm and 2.0 mm in thickness and is ulcerated, or it is between 2.01 and 4.0 mm and is not ulcerated. It appears to be localized in the skin and has not been found in lymph nodes or distant organs. Stage IIB: The melanoma is between 2.01 mm and 4.0 mm in thickness and is ulcerated, or it is thicker than 4.0 mm and is not ulcerated. It appears to be localized in the skin and has not been found in lymph nodes or distant organs. Stage IIC: The melanoma is thicker than 4.0 mm and is ulcerated. It appears to be localized in the skin and has not been found in lymph nodes or distant organs. Stage III: The melanoma has spread to lymph nodes nearest the affected skin area. There is no distant spread. Stage IV: The melanoma has spread beyond the original area of skin and the nearby lymph nodes to other organs, such as the lung, liver, or brain, or to distant areas of the skin or lymph nodes. 12

15 Types of Treatment for Melanoma After the diagnostic tests are done, your cancer care team will recommend one or more treatment options. Consider the options without feeling rushed. If there is anything you do not understand, ask to have it explained. The choice of treatment depends largely on the thickness of the primary tumor and the stage of the disease. Types of Surgery for Melanoma Wide local excision When the diagnosis of melanoma is established by biopsy, a wide local excision is done to decrease the chance of local recurrence. More tissue is removed around the melanoma site, and the tissue from the final excision is examined to make sure that no cancer cells remain in the skin. The size of the margin depends on the thickness of the tumor. Tumor thickness In situ Less than 1 mm Recommended margins 0.5 cm (1 inch = 2.54 cm) 1 cm 1 to 2 mm 1 to 2 cm 2 to 4 mm 2 cm Over 4 mm At least 2 cm Amputation If the melanoma is on a finger or toe, the treatment may be to amputate as much of that digit as is necessary to obtain clear margins. Lymph node evaluation After the diagnosis of melanoma is made, the doctor will examine the lymph nodes nearest the melanoma. If the lymph nodes are not enlarged, then a sentinel node biopsy procedure may be done. A sentinel lymph node is usually considered if the melanoma is >1 mm thick. If the sentinel lymph node does not show cancer, then it is unlikely the melanoma has spread to the lymph nodes; there is no need for a lymph node dissection. If the sentinel lymph node is positive, removal of the remaining lymph nodes is usually advised. If the regional lymph nodes feel hard or large, and FNA or biopsy shows metastatic melanoma, a lymph node dissection may be done. This procedure removes most of the lymph nodes in that area, and they will be examined under a microscope to see how many lymph nodes contain cancer. Lymph node dissection can cause some side effects that may be permanent. The most troublesome is called lymphedema. Lymph nodes in the groin or under the arm help drain fluid from the limbs. Without them, fluid may collect. Most patients do not get lymphedema. Elastic stockings or sleeves can help some people with this condition. Sometimes special devices that squeeze the limbs are used and may be helpful. These side effects, along with the discomfort from the surgery itself, are why this procedure is not done unless the doctor thinks it is necessary. Discuss risks of these side effects with your doctor. 13

16 Surgery for Metastatic Melanoma Once melanoma has spread from the skin to distant organs (such as the lungs or brain), the cancer is unlikely to be curable by surgery. Even when only 1 or 2 metastases are found by imaging studies such as CT or MRI scans, other areas of metastasis are likely to be present that are too small to be found by these scans. Surgery is sometimes done in these circumstances. If one or even a few metastases are present and can be completely removed, this surgery may help some patients to live longer. Also, removing a single metastasis in the brain that might eventually cause symptoms may help improve the patient s quality of life. Chemotherapy for Melanoma Systemic chemotherapy uses anticancer drugs that are usually injected into a vein or given by mouth. These medications travel through the bloodstream to all parts of the body, where they attack cancer cells that have already spread beyond the skin to involve lymph nodes and other organs. Chemotherapy drugs kill cancer cells but also kill some normal cells, such as the bloodproducing cells of the bone marrow, the cells lining the gastrointestinal tract, and cells of hair follicles. Temporary side effects of systemic chemotherapy might include nausea and vomiting, loss of appetite, loss of hair, and mouth sores. Because chemotherapy can kill normal blood cells, patients may have low blood cell counts, which can result in: an increased chance of infection (due to a shortage of white blood cells) bleeding or bruising after minor cuts or injuries (due to a shortage of blood platelets) fatigue (often due to low red blood cell counts but also can be caused by the chemotherapy alone) Most side effects disappear once treatment is stopped. There are treatments for many of the temporary side effects of chemotherapy, so be sure to discuss side effects with your cancer care team. For example, anti-nausea drugs can be given to prevent or reduce nausea and vomiting. Only a few chemotherapy drugs are used for stage IV melanoma. Although chemotherapy is usually not as effective in melanoma as in some other types of cancer, it may relieve symptoms or extend survival of some patients with stage IV melanoma. Chemotherapy drugs often used to treat melanoma include: DTIC, alone or with other chemotherapy drugs such as BCNU and cisplatin. The combination of these 3 chemotherapy drugs, occasionally together with tamoxifen (a hormonal therapy drug most often used to treat breast cancer) is called the Dartmouth regimen. Cisplatin, vinblastine, and DTIC is another chemotherapy combination for treating melanoma. Temozolomide is a new drug that works like DTIC, but it can be given in the form of a pill. These chemotherapy drugs may also be combined with immunotherapy drugs, such as interferon-alpha and/or interleukin-2 (see the section on immunotherapy). 14

17 Hyperthermic isolated limb perfusion is a type of chemotherapy sometimes used for treating metastatic melanomas confined to the arm or leg. This method temporarily separates the circulation of the involved limb from the rest of the body and injects high doses of chemotherapy into the artery feeding the limb. This allows high doses to be given to the area of the tumor without exposing internal organs to these doses that would otherwise cause severe side effects. Usually the fluid is warmed to 102 to 104 Fahrenheit. Melphalan is the drug most often used in this chemotherapy procedure. Limb perfusion is done to help control disease in the affected extremity and is not thought to improve survival. Radiation Therapy Radiation therapy uses high-energy rays or particles to kill cancer cells. External beam radiation therapy focuses radiation from outside the body on the skin tumor. This type of radiation therapy is used for treating some patients with melanoma. Radiation therapy is not commonly used to treat the primary tumors of melanoma (the original melanoma that developed on the skin). But it may be considered in some patients and in patients whose melanoma has come back. Immunotherapy Immunotherapy enhances and encourages a patient s immune system to recognize and destroy cancer cells more effectively. Several types of immunotherapy are used in treating patients with melanoma. Some are being studied as adjuvant therapy. Adjuvant therapy is treatment given after surgery, either chemotherapy or radiation therapy, with the intent of destroying any cancer cells that may not have been removed by the surgery. Cytokine therapy Cytokines are proteins that activate the immune system in a general way. Two cytokines, interferon-alpha and interleukin-2, can help boost immunity in patients with melanoma. Both drugs can help shrink metastatic (stage III and IV) melanoma in about 10% to 20% of patients. Side effects of cytokine therapy may include fever, chills, aches, depression, and severe tiredness. Interleukin-2, particularly in high doses, can cause fluid to accumulate in the body, so the person swells up and can feel quite sick. Some patients may need to be hospitalized because of this problem. Interferon-alpha-2b Patients with deeper melanomas often have cancer cells that break away from the primary melanoma and travel to other parts of the body. Interferons are immune substances produced by the body in response to infection. Interferon-alpha-2b can be used as an adjuvant therapy. Side effects include fever, chills, aches and severe tiredness. Interferonalpha-2b can also have effect on the heart and liver, and patients should be followed by an oncologist who is experienced with this treatment. Interferon-alpha-2b given to patients with stage III melanoma following surgery can delay the recurrence of melanoma but may not prolong patients lives. Decisions about adjuvant therapy by patients and their doctors should take into account the potential benefits and side effects of this treatment. 15

18 Vaccine therapy Melanoma vaccines are experimental therapies that are being tested in patients with stage III or stage IV melanoma. Antimelanoma vaccines are, in some ways, similar to the vaccines used to prevent diseases caused by viruses such as polio, measles, and mumps. Antivirus vaccines usually contain weakened or killed viruses or parts of a virus that cannot cause the disease. The vaccine stimulates the body s immune system to destroy the more harmful type of virus. In the same way, weakened melanoma cells or parts of melanoma cells called antigens can be injected into a patient in an attempt to stimulate the body s immune system to destroy melanoma cells. Usually, the melanoma cells are mixed with substances that help stimulate the body s immune system. Direct tumor injections Sometimes melanomas will shrink and go away if they are injected with certain substances. The substances used most often are interferon and BCG, a form of killed tuberculosis that is used to immunize people against tuberculosis. This treatment is not used often. CO2 laser ablation This treatment may be used in some patients with several small skin metastatic melanomas. The CO2 laser is a type of laser used for skin problems. It emits a very high energy beam that destroys superficial skin lesions. Supportive Care Most of this document discusses ways to cure people with melanoma or to help them live longer by removing or destroying melanoma cancer cells. However, another important goal is to help you feel as well as you can and to continue to do the things in life that you want to do. Don t hesitate to discuss your symptoms or how you are feeling with your cancer care team. There are effective and safe ways to treat symptoms you may be having, as well as most of the side effects caused by treatment for melanoma. Pain is a concern for patients with advanced cancer. Growth of the cancer around certain nerves may cause severe pain. It is important that patients not hesitate to tell their doctors if they have pain. For most patients, treatment with morphine or other opioids (prescription medicines that are the strongest pain relievers available) will reduce the pain considerably. For more information on the treatment of cancer pain, you may contact the American Cancer Society to request a copy of the Cancer Pain Treatment Guidelines for Patients. Complementary and Alternative Therapies Complementary and alternative medicines are a group of different types of health care practices, systems, and products that are not part of your usual medical treatment. They may include Chinese herbs, special supplements, acupuncture, massage, and a host of other types of treatment. You may hear about different treatments from your family and 16

19 friends. People may offer all sorts of things, such as vitamins, herbs, stress reduction, and more as a treatment for your cancer or to help you feel better. Some of these treatments are harmless in certain situations, while others have been shown to cause harm. Most of them are of unproven benefit. The American Cancer Society defines complementary medicine or methods as those that are used in addition to your regular medical care. If these treatments are carefully managed, they may add to your comfort and well-being. Alternative therapies are defined as those that are used instead of your regular medical care. Some of them have been proven harmful, but are still promoted as cures. If you choose to use these alternatives, they may reduce your chance of fighting your cancer by delaying or replacing regular cancer treatment. There is a great deal of interest today in complementary and alternative treatments for cancer. Many are being studied to find out if they are truly helpful to people with cancer. Before changing your treatment or adding any of these methods, it is best to discuss this openly with your doctor or nurse. Some methods can be safely used along with standard medical treatment. Others, however, can interfere with standard treatment or cause serious side effects. That is why it's important to talk with your doctor. More information about complementary and alternative methods of cancer treatment is available through the American Cancer Society s toll-free number at ACS-2345 or on our Web site at About Clinical Trials Studies of promising new or experimental treatments in patients are known as clinical trials. A clinical trial is only done when there is some reason to believe that the treatment being studied may be valuable to the patient. Treatments used in clinical trials are often found to have real benefits. Researchers conduct studies of new treatments to answer the following questions: Is the treatment helpful? How does this new type of treatment work? Does it work better than other treatments already available? What side effects does the treatment cause? Are the side effects greater or less than the standard treatment? Do the benefits outweigh the side effects? In which patients is the treatment most likely to be helpful? There are 3 phases of clinical trials in which a treatment is studied before it can be approved by the FDA (Food and Drug Administration). Phase I clinical trials: The purpose of a phase I study is to find the best way to give a new treatment and how much of it can be given safely. Doctors watch patients carefully for any harmful side effects. The treatment has been well tested in laboratory and animal studies, but the side effects in patients are not completely known. Doctors conducting the clinical trial start by giving very low doses of the drug to the first patients and increasing 17

20 the dose for later groups of patients until side effects appear. Although doctors are hoping to help patients, the main purpose of a phase I study is to test the safety of the drug. Phase II clinical trials: These studies are designed to see if the drug works. Patients are given the highest dose that doesn t cause severe side effects (determined from the phase I study) and closely observed for an effect on the cancer. The doctors also look for side effects. Phase III clinical trials: Phase III studies involve large numbers of patients. Some clinical trials enroll thousands of patients. One group (the control group) receives the standard (most accepted) treatment. The other groups receive the new treatment. Usually doctors study only 1 new treatment to see if it works better than the standard treatment, but sometimes they test 2 or 3. All patients in phase III studies are closely watched. The study will be stopped if the side effects of the new treatment are too severe or if one group has had a much better result than the others. If you are in a clinical trial, you will have a team of experts taking care of you and monitoring your progress very carefully. The study is especially designed to pay close attention to you. However, there are some risks. No one involved in the study knows in advance whether the treatment will work or exactly what side effects will occur. That is what the study is designed to discover. While most side effects disappear in time, some can be permanent or even life threatening. Keep in mind, though, that even standard treatments have side effects. Depending on many factors, you may decide to enroll in a clinical trial. Deciding to enter a clinical trial Enrollment in any clinical trial is completely up to you. Your doctors and nurses will explain the study in detail to you and will give you a form to read and sign indicating your desire to take part. This process is known as giving your informed consent. Even after signing the form and after the clinical trial begins, you are free to leave the study at any time, for any reason. Taking part in the study will not prevent you from getting other medical care you may need. To find out more about clinical trials, talk to your cancer care team. Among the questions you should ask are: Is there a study I would be eligible for? What is the purpose of the study? What kinds of tests and treatments does the study involve? What does this treatment do? Will I know which treatment I will receive? What is likely to happen in my case with, or without, this new research treatment? What are my other choices and their advantages and disadvantages? How could the study affect my daily life? What side effects can I expect from the study? Can the side effects be controlled? Will I have to be hospitalized? If so, how often and for how long? Will the study cost me anything? Will any of the treatment be free? If I am harmed as a result of the research, what treatment would I be entitled to? What type of long-term follow-up care is part of the study? Has the treatment been used to treat other types of cancers? 18

21 The American Cancer Society offers a clinical trials matching service for patients, their family, and friends. You can gain access to this service through the ACS cancer information center (1-800-ACS-2345) or our Web site ( Based on the information you provide about your cancer type, stage, and previous treatments, this service compiles a list of clinical trials that match your medical needs. In finding a center most convenient for you, the service can also take into account where you live and whether you are willing to travel. You can also get a list of current clinical trials by calling the National Cancer Institute s Cancer Information Service toll free at CANCER, or by visiting the NCI clinical trials Web site Participating in a clinical trial may help you directly, and it may help other people with melanoma in the future. For these reasons, the NCCN and the ACS are committed to conducting clinical trials and helping people with cancer learn more about these studies. Other Things to Consider During and After Treatment During and after treatment, you may be able to hasten your recovery and improve your quality of life by taking an active role in your care. Learn about the benefits and disadvantages of each of your treatment options, and ask questions of your cancer care team if there is anything you do not understand. Learn about and look out for side effects of treatment, and report these promptly to your cancer care team so that they can take steps to help relieve them. Remember that your body is as unique as your personality and your fingerprints. Although understanding your cancer s stage and learning about your treatment options can help predict what health problems you may face, no one can say precisely how you will respond to cancer or its treatment. You may have special strengths such as a history of good nutrition and being physically active, a strong family support system, or a deep faith, and these strengths may make a difference in how you respond to cancer. In fact, behavioral scientists have recently found that some people who took advantage of a social support system, such as a cancer support group, survived with a better quality of life. There are also experienced professionals in mental health services, social work services, and pastoral services who may assist you in coping with your illness. You can also help in your own recovery from cancer by making healthy lifestyle choices. If you use tobacco, stop now. Quitting will improve your overall health, and the full return of the sense of smell may help you enjoy a healthy diet. If you use alcohol, limit how much you drink. Have no more than 1 drink per day if you are a woman or 2 drinks per day if you are a man. Good nutrition can help you get better after treatment. Eat a nutritious and balanced diet, with plenty of fruits, vegetables, and whole grain foods. Ask your cancer care team if you could benefit from a special diet. They may have specific suggestions for people who have had radiation therapy, chemotherapy, or surgery. 19

22 If you are in treatment for cancer, be aware of the battle that is going on in your body. Radiation therapy, cytokine therapy, and chemotherapy all add to the fatigue that can be caused by the disease itself if it has spread. Give your body the rest it needs so that you will feel better as time goes on. Exercise once you feel rested enough. Ask your cancer care team whether your cancer or its treatments might limit your exercise program or other activities. Surgery and radiation therapy may sometimes affect your feelings about your body and may lead to specific physical problems that affect sexuality. Your cancer care team can help with these issues, so don t hesitate to share your concerns. A cancer diagnosis and its treatment are major life challenges, affecting you and everyone who cares for you. Before you reach the point of feeling overwhelmed, consider attending a meeting of a local support group. If you need assistance in other ways, contact your hospital s social service department or the American Cancer Society for help in contacting counselors or other services. Protecting Your Skin From Sun Exposure Everyone needs to protect his or her skin from the harmful effects of the sun. Sunlight contains ultraviolet radiation (UV), which can damage the genes in your skin cells. Tanning lamps and booths are another source of ultraviolet radiation. Excessive exposure to light from these sources can increase the risk to skin cancer, including melanoma. The amount of UV exposure depends on the intensity of the radiation, length of time the skin was exposed, and whether the skin was protected with clothing and sunscreen. The most important ways to protect your skin is by avoiding being outdoors in intense sunlight too long and to protect your skin when you are outdoors. You can maintain your level of physical activity and protect your skin at the same time with the following: Seeking shade: The simplest and most effective way to limit exposure to ultraviolet (UV) light is to avoid being outdoors in sunlight too long. This is most important in the middle of the day when UV light is most intense. Protecting your skin with clothing: You can protect most of your skin with clothing, including a shirt with long sleeves and a hat with a broad brim. Tightly woven and darkly colored (especially blue) fabrics generally provide the best sun protection. Using sunscreen: Sunscreens with an SPF (Sun Protection Factor) of 15 or more should be used on areas of skin exposed to the sun, particularly when the sunlight is strong. Always follow directions when applying sunscreen. You should apply sunscreen before you go outside, use it thickly on all sun-exposed skin, and reapply it every 2 hours. A 1-ounce application (a palmful of sunscreen) is recommended. Many sunscreens wear off with sweating and swimming and must be reapplied for maximum effectiveness. Use sunscreen even on hazy days or days with light or broken cloud cover because the UV light still comes through. 20