Skin cancer is the most common cancer in the United States.

Basal cell carcinoma (BCC) is the most common type of skin cancer, followed by squamous cell carcinoma (SCC) and melanoma. In this e-booklet, we’ll discuss the standard and new treatment approaches to advanced, or metastatic, skin cancers—those that have spread from their original location on the skin to other parts of the body. We’ll also discuss how to manage treatment-related side effects and the best ways to care for your skin during treatment.

Basal Cell and Squamous Cell Carcinomas

Symptoms of localized (non-advanced) BCC and SCC can vary by individual, but often one of the first signs is a persistent skin growth, bump or sore; for this discussion, we’ll refer to all these skin conditions as tumors.

A BCC that appears on the head or neck may look like a pale patch of skin, or a waxy translucent (clear) bump, frequently with fine blood vessels within it. If a BCC develops elsewhere, it may look like a flesh-colored lesion. A characteristic of a BCC is its smooth appearance.

The lumps associated with SCC are firm, and may be rough on the surface; they can also develop as a reddish scaly patch. These lumps or patches are typically found on the head, neck, hands, or arms, but they can also develop in other areas.

As the appearance of BCC and SCC do vary, it’s important that you discuss any suspicious-looking patch of skin with your primary care physician or dermatologist.

There are a number of factors that increase the risk of developing BCC or SCC; the most significant is excessive exposure to ultraviolet (UV) radiation, either from the sun or from tanning beds. Having had one or more severe sunburns (with blistering) at any point in your life is an additional risk factor.

Treatment Approaches for Advanced BCC and SCC

At the time of diagnosis, most basal and squamous cell cancers have not spread from their original location, and are managed with local treatments, which include resection (removal) of the tumor and the use of topical medications (medications applied to the skin). While less common, radiation therapy may be considered for more difficult cases, in which neither resection nor topical medications is an option.

In advanced cases of BCC and SCC, the tumor spreads, affecting other areas of the body. Resection may be more difficult or even impossible, and radiation may not be an option. It is in these situations that a medical oncologist may become part of your health care team, and the use of oral or intravenous (through the vein) drugs will be considered as a way to destroy the cancer. Drugs differ, based on whether the cancer is basal cell or squamous cell.

Advanced basal cell cancer

Basal cell cancers are the most common type of skin cancer, accounting for approximately eight out of every ten nonmelanoma skin cancers.

Several years ago, researchers discovered that more than 70 percent of BCCs have certain gene mutations (changes) in what is called the “Hedgehog pathway.” These changes activate the growth of the basal cell cancer cells and allow for their survival. Finding the mutations meant that drugs could be designed to target those pathways.

Vismodegib (Erivedge) is a Hedgehog pathway inhibitor; it was the first drug approved by the U.S. Food and Drug Administration (FDA) for adults with BCC that has spread to other parts of the body, comes back after surgery, or cannot be treated with surgery or radiation. Vismodegib is a targeted treatment; it is designed to target the specific cell mechanisms that are important for the growth and survival of tumor cells.

Vismodegib is a capsule taken by mouth once a day. It’s recommended that patients continue to take vismodegib for as long as it continues to work for them, and any side effects are able to be tolerated. In the largest study so far of vismodegib in advanced BCC, the tumors shrank in most people. In a few patients, the tumors disappeared for a period of time. New studies are underway to see how vismodegib can be used before or after surgery to allow for a smaller resection procedure (removal of tumor), and faster healing.

People with a rare disease that is present at birth called basal cell nevus syndrome (also known as Gorlin syndrome) can have up to hundreds of basal cell skin cancers. In clinical trials, nearly all the tumors disappeared after patients with this syndrome took vismodegib for several months. That is important news because surgery and radiation are not possible in many of these cases. But some people with this type of BCC can benefit from surgery. In a small clinical trial, 10 such patients were given vismodegib before surgery. Their tumors shrank, resulting in a more confined surgery, and they healed faster.

In July 2015, the FDA approved sonidegib (Odomzo) for the treatment of patients with locally advanced basal cell carcinoma that has recurred following surgery or radiation therapy, or those who are not candidates for surgery or radiation therapy.

The development and approval of vismodegib and sonidegib has launched additional research efforts, which may lead to the creation of new drugs to treat basal cell cancers.

Chemotherapy is not typically used to treat advanced basal cell cancers.

Advanced squamous cell cancer

Advanced squamous cell skin cancer is rare, and there have been few clinical trials. There is much more data available on squamous cell cancer of the head and neck, and the FDA has approved the targeted treatment cetuximab (Erbitux) for those cancers; it is also approved for the treatment of certain types of colorectal cancer. Cetuximab can block one of the signals that tells a tumor to grow by attaching to a structure on the cell called the epidermal growth factor receptor (EGFR).

Clinical trials now show that cetuximab given through a vein is also effective in treating advanced squamous cell carcinomas of the skin. If a drug has been approved for one use, doctors may choose to use the drug for other conditions, if they believe it may be helpful. Doctors are already prescribing cetuximab to some patients with SCCs whose tumors cannot be surgically removed or treated with radiation.

Chemotherapy drugs are sometimes considered to treat advanced cases of squamous cell cancer. These drugs are given intravenously (into a vein), usually once every few weeks. They can often slow the spread of the cancer and relieve some symptoms; in some cases, they may shrink tumors enough so that other treatments such as surgery or radiation can be used.

Melanoma

Most cases of melanoma are diagnosed at an early stage, with the tumor—often a single, thin spot or lesion—located on the skin. In the majority of patients, the melanoma is effectively treated by resection (removal) of the tumor. But in some cases, the cancer can come back and spread. When melanoma does spread, or metastasize, surgery and radiation are less effective. Until recently, few medications were available to treat advanced melanoma.

In the past few years, a number of drugs to treat metastatic melanoma have been approved by the FDA, and others are likely to be approved in the future. The treatments work either by helping the immune system destroy melanoma cells (immunotherapy) or blocking their ability to grow, divide and spread (targeted treatments).

Treatment

A physical exam and imaging tests are used to determine if the cancer has spread and, if so, to where. These tests can include an MRI of the brain, a CT scan of the chest, abdomen, and pelvis, and a whole-body PET scan.

Deciding what treatment option is best is based on factors unique to the individual patient; including their health history, energy level, where the cancer appeared initially, and where it appears currently.

There are now many different treatment options for metastatic melanoma; it’s important for patients to ask questions of their health care team to understand what treatment may be most effective for them.

Immunotherapies

Aldesleukin (interleukin-2, Proleukin). Since the late 1990s, aldesleukin has been approved as a standard treatment for metastatic (advanced) melanoma. It is given through a vein. Aldesleukin helps the body’s immune system shrink and destroy tumors more effectively. But aldesleukin is not used as commonly today because there are newer and more effective treatments.

Ipilimumab (Yervoy). Ipilimumab was approved by the FDA in 2011 for treatment of metastatic melanoma. This drug, given through a vein, helps the immune system in a different way from aldesleukin. Ipilimumab seeks out and locks onto CTLA 4 (cytotoxic T-lymphocyte associated protein 4), a protein that normally helps keep immune system cells (called T cells) in check. By blocking the action of CTLA-4, ipilimumab is thought to help the immune system destroy melanoma cells. The first such medication approved for treating people with melanoma, it is given once every three weeks, for a total of four doses. It can take from one to four months before ipilimumab begins to work.

Pembrolizumab (Keytruda). Given through a vein, pembrolizumab is the first approved drug that blocks a cellular pathway known as PD-1 (programmed cell death receptor 1). The PD-1 pathway restricts the body’s immune system from attacking melanoma cells. It was approved for treatment of metastatic melanoma in September 2014.

Nivolumab (Opidvo). Like pembrolizumab, nivolumab works by blocking the PD-1 pathway; it is also given through a vein. Nivolumab was approved for the treatment of metastatic melanoma in December 2014.

Both pembrolizumab and nivolumab are intended for patients who have been previously treated with ipilimumab and, for melanoma patients whose tumors express a gene mutation called BRAF V600, for use after treatment with ipilimumab and a BRAF inhibitor.

In October 2015, the combination of ipilimumab and nivolumab was approved for the treatment of advanced melanoma. This combination has been shown to be more effective in treating advanced melanoma compared to either of the agents alone. However, the rate of possible side effects is also increased.

Targeted Treatments

Targeted treatments are designed to target the specific cell mechanisms that are important for the growth and survival of tumor cells.

About one-half of all melanomas have a mutation in the gene called BRAF that leads to tumor growth. For these melanomas, these targeted treatments have been approved by the FDA:

Vemurafenib (Zelboraf). Many patients who take vemurafenib survive longer; their tumors shrink within a matter of weeks and take longer to begin growing again. Vemurafenib, a tablet taken by mouth, can shrink tumors in areas of the body such as the liver, bowel, and bone that are difficult to treat with chemotherapy or surgery. In November 2015, the FDA approved cobimetinib (COTELLIC) for the treatment of patients with unresectable or metastatic melanoma with a BRAF V600E or V600K mutation, in combination with vemurafenib.

Dabrafenib (Tafinlar) and trametinib (Mekinist). These drugs, taken by mouth as tablets, block the same growth pathway as vemurafenib. Dabrafenib targets the BRAF protein, whereas trametinib blocks another protein called MEK, which is “switched on” by BRAF. In January 2014, their combined use was approved by the FDA to treat patients with metastatic melanoma that that cannot be removed by surgery. Mekinist and Tafinlar are the first drugs approved for combination treatment of melanoma.

In addition to BRAF, there are also other mutations that may lead to melanoma growth, and researchers are learning how best to block them:

Imatinib (Gleevec) and sunitinib (Sutent). About 3 percent of melanomas have mutations in a gene called C-KIT, a protein found on the surface of many different types of cells. C-KIT is a type of receptor which is found on some healthy cells as well as tumor cells. (A receptor is a molecule on the surface of a cell. Receptors are switched on when a specific substance attaches to them, causing an action in the cell.) When switched on normally, C-KIT receptors tell the cell to grow when it is needed. But in some types of melanoma, the C-KIT receptors are always switched on, making the cell grow uncontrollably into cancer. Clinical trials are showing that the targeted therapies imatinib and sunitinib (both of which are FDA-approved to treat other cancers and are given by mouth) can block the mutated C-KIT receptor. With these drugs, melanoma tumors with the C-KIT mutation shrink and can be controlled for longer periods of time.

Managing Treatment Side Effects

All cancer treatments can cause side effects. It’s important that you report any side effects you experience to your health care team so they can help you manage them. Report them right away—don’t wait for your next appointment. Doing so will improve your quality of life and help ensure you stick with your treatment plan.

Common side effects for various treatment options are shared in this section. Fatigue, digestive tract problems, and loss of appetite can occur with any type of treatment, and are discussed separately. It’s important to remember that not all patients experience all side effects, and patients may experience side effects not listed here.

Side effects of radiation treatments

Changes to the skin are the most common side effects of radiation; those changes can include dryness, swelling, peeling, redness, and blistering. To help prevent these side effects, apply a topical corticosteroid cream to the area being treated. It’s best to do this a few hours before each treatment.

It’s especially important to contact your health care team if there is any open skin or painful areas, as this could indicate an infection. Infections can be treated with an oral antibiotic or topical antibiotic cream.

Side effects of chemotherapy

The side effects of chemotherapy depend on the type and dose of drugs given and the length of time they are used, and can include:

  • Hair loss
  • Mouth sores
  • Increased risk of infection (from having too few white blood cells)
  • Easy bruising or bleeding (from having too few blood platelets)

Side effects of vismodegib, in treatment of BCC

Many patients remain on the targeted treatment vismodegib for months or even years, and it is generally considered very tolerable. However, there are side effects that patients should be aware of:

Muscle cramps and spasms. About 70 percent of people on vismodegib develop muscle cramps or spasms, which can be severe. These most frequently occur in the legs and hands, and are usually worse at night. Heating pads and musclestretching may help. Your doctor can prescribe anti-spasm or pain medications, if needed. Make sure your doctor knows what other medications you may be taking.

Change in taste. About half the people who take vismodegib develop a metallic or cardboard-like taste in their mouth. Your doctor or a registered dietitian can suggest a specific diet to help ease this side effect. It’s important to eat enough to maintain a healthy weight, as too much weight loss can lead to or worsen fatigue.

Thinning hair. Using vismodegib can lead to thinning hair or complete hair loss. There are various ways to camouflage thin hair, including sprays and powders. Over-the-counter minoxidil foam or liquid (Rogaine and others) may help to trigger hair regrowth.

Side effects of cetuximab, in treatment of SCC

Rash. Many people who take cetuximab get an itchy rash on their face and upper body, and sometimes their scalp. It may it may look like acne and may cause pain. For the acne-like rash, your doctor may prescribe oral antibiotics and corticosteroid creams.

Inflammation around the fingernails and toenails. About 20 percent of people treated with cetuximab develop redness and swelling around the nail folds (where the nail meets the skin). This condition can be treated with topical or oral antibiotics, topical steroid creams or ointments, and, if needed, a small surgical procedure.

Hair changes. Cetuximab, and other drugs in its class, can cause the hair to become very curly. Women may lose some hair on their scalp or develop hair growth on the face. Because the skin is made sensitive by anti-cancer medication, doctors discourage the use of chemical hair removal or waxing.

Side effects of melanoma treatments

Rash. Many people who take immunotherapies or targeted treatments get an itchy rash on their face and upper body and sometimes their scalp. With ipilimumab and vemurafenib, the rash is red, flat, or raised, and usually affects the trunk (the main part of the body, not including the head or limbs); topical or oral corticosteroids are usually used to treat this rash. On rare occasions, the rash may blister. These rashes usually occur within the first two months of treatment. Once the rash is treated and has improved, it usually does not come back as severely. Avoid scratching a rash, as it can lead to infection. Ask your doctor about using over-the-counter medications that can help; but in general prescription medications are more effective.

Sensitivity to sunlight. Some drugs, such as vemurafenib, can increase the risk of getting sunburned. It’s always a good idea to reduce your exposure to sunlight, if you are unprotected by sunscreen. You can get sunburned even through the glass in your car or home, so it’s important to always use sunscreen, especially between 10 a.m. and 4 p.m., and avoid prolonged exposure to direct sunlight.

Spots on the skin. Some people taking vemurafenib and dabrafenib may develop red or pink skin bumps. These bumps, a type of early-stage squamous cell skin cancer called a keratoacanthoma, can appear suddenly or start to grow quickly. Report them to your doctor right away so they can be examined and removed.

Hand-foot syndrome. Some patients taking treatments that target BRAF (such as vemurafenib or dabrafenib) develop tenderness, redness, and/or thickening of the palms and soles that look like calluses. If you experience these side effects, it’s important to use a moisturizer containing urea, ammonium lactate or salicylic acid. Try to avoid placing pressure or friction on your hands and feet by wearing well-padded socks and soft shoes and slippers made with memory foam or calfskin. A podiatrist can help remove thickened calluses or treat painful areas. If tenderness or inflammation becomes severe, talk to your doctor about using topical corticosteroid creams or pain medications such as patches containing lidocaine.

Changes in bowel habits. If you are taking ipilimumab, it’s very important to tell your doctor if you experience increased gassiness, bloating, diarrhea or other changes in bowel habits. He or she may prescribe medications for these symptoms and/or change your diet. These side effects should be treated early to avoid more serious problems, such as dehydration or damage to the intestines.

Managing fatigue

Fatigue (extreme tiredness not helped by sleep) is one of the most common side effects of many cancer treatments. If you are taking a medication that causes you to experience fatigue, talk to your doctor about whether taking a smaller dose is right for you.

There are a number of other tips for reducing fatigue:

  • Take several short naps or breaks.
  • Take short walks or do some light exercise, if possible.
  • Try easier or shorter versions of the activities you enjoy.
  • Ask your family or friends to help you with tasks you find difficult or tiring.
  • Save your energy for things you find most important.

Fatigue can be a symptom of other illnesses, such as diabetes, thyroid problems, heart disease, rheumatoid arthritis, and depression. So be sure to ask your doctor if he or she thinks any of these conditions may be contributing to your fatigue.

Also, it could be very valuable to talk to an oncology social worker or oncology nurse. These professionals can also help you manage fatigue. They can work with you to manage any emotional or practical concerns that may be causing symptoms and help you find ways to cope.

Managing digestive tract symptoms

Digestive tract symptoms can occur in people undergoing cancer treatments. Your doctor can prescribe medications for digestive tract side effects; the following tips also may help.

Nausea and vomiting:

• Avoid food with strong odors, as well as overly sweet, greasy, fried, or highly seasoned food.

• Eat meals cold or at room temperature, which often makes food more easily tolerated.

• Nibble on dry crackers or toast. These bland foods are easy on the stomach. Having something in your stomach when you take medication may help ease nausea.

Diarrhea:

• Drink plenty of water. Ask your doctor about using drinks such as Gatorade which provide electrolytes as well as liquid. Electrolytes are body salts that must stay in balance for cells to work properly.

• Over-the-counter medicines such as loperamide (Imodium A-D and others) and prescription drugs are available for diarrhea but should be used only if necessary. If the diarrhea is bad enough that you need medicine discuss it with your doctor or nurse.

• Avoid sweetened foods and alcohol.

• Choose fiber-dense foods such as whole grains, fruits and vegetables, all of which help form stools.

Managing loss of appetite:

• Because it’s important to maintain your weight, eat small meals throughout the day. That’s an easy way to take in more calories and protein.

• To keep from feeling full early, avoid liquids with meals or take only small sips (unless you need liquids to help swallow). Drink most of your liquids between meals.

• Be as physically active as you can. Sometimes, taking a short walk an hour or so before meals can help you feel hungry.

• Keep high-calorie, high-protein snacks on hand such as hard-boiled eggs, peanut butter, cheese, ice cream, granola bars, liquid nutritional supplements, puddings, nuts, canned tuna, or trail mix.

• Eat your favorite foods any time of the day. For example, if you like breakfast foods, eat them for dinner.

Your Health Care Team

As you manage your skin cancer, it’s important to remember that you are a consumer of health care. The best way to make decisions about health care is to educate yourself about your diagnosis and the members of your health care team, including nurses, social workers and patient navigators.

Start a health care journal. Having a health care journal or notebook will allow you to keep all of your health information in one place. You may want to write down the names and contact information of the members of your health care team, as well as any questions for your doctor. Keep a diary of your daily experiences with cancer and treatment. You can separate your journal or notebook into different sections to help keep it organized.

Prepare a list of questions. Before your next medical appointment, write down your questions and concerns. Because your doctor may have limited time, you should ask your most important questions first, and be as specific and brief as possible.

Bring someone with you to your appointments. Even if you have a journal and a prepared list of questions or concerns, it’s always helpful to have support when you go to your appointments. The person who accompanies you can serve as a second set of ears. He or she may also think of questions to ask your doctor or remember details about your symptoms or treatment that you may have forgotten.

Write down your doctor’s answers. Taking notes will help you remember your doctor’s responses, advice, and instructions. If you cannot write down the answers, ask the person who accompanies you to do that for you. If you have a mobile device, you can use it to take notes. Writing notes will help you review the information later.

Record your visit if your doctor allows it. Recording the conversation with your doctor gives you a chance to hear specific information again or share it with family members or friends.

Incorporate other health care professionals into your team. Your oncologist and oncology nurse are essential members of your health care team, but there are other health care professionals can help you manage your diagnosis and treatment:

• Your primary care physician should be kept updated about your skin cancer treatment and any test results.

• Your local pharmacist is a great source of knowledge about the medications you are taking; have all of your prescriptions filled at the same pharmacy to avoid the possibility of harmful drug interactions.

• Make sure your oncologist knows of any other medical conditions you have, or any pain you are experiencing, so that they can consult with your primary care physician or your specialist if needed.

Remember, there is no such thing as over-communication. Your health care team wants to know about how you’re feeling overall, which includes your level of of pain, your energy level, your appetite, and your mood and spirits.

Frequently Asked Questions

Q. What can I do to get ready for my skin cancer treatment? How do I prepare myself?

A. Maintaining a good “performance status”—the ability to carry out ordinary tasks and daily activities—is an important part of preparing for cancer treatment and the challenges you may face. Light exercise and healthy eating can help you cope better with your treatment. Ask your doctor to recommend a registered dietitian and an exercise specialist to help you come up with a plan that works for you. It’s also important to include mental preparation. Talk to your doctor or nurse about what to expect. If you are feeling anxious or distressed and need support outside of your network of family and friends, work with an oncology social worker to address your concerns.

Q. Can you explain what the “ABCDEs” of melanoma are and why they’re important?

A. If you have any moles with the following features, ask your doctor to check them out. Such changes in the appearance of a mole may be the first signs of melanoma. If recognized and treated early, this cancer is almost always successfully treated.

  • Asymmetrical: One side of the mole looks different from the other
  • Border: Irregular or vaguely defined borders
  • Color: Uneven coloring or multiple colors
  • Diameter: Larger than a pencil eraser or growing in size
  • Evolution: Growing or changing in any way

Q. Can basal and squamous cell skin cancers recur?

A. Yes. Having had one BCC or SCC increases the chance of having another, especially in the same skin area or nearby.

Q. What is Mohs surgery and should I have it to remove my tumor?

A. Mohs surgery is designed to resect (remove) BCC and SCC tumors with minimal resection of normal tissue. Talk to your dermatologist or surgeon to see if this is an appropriate option for you.

Q. Is there a link between melanoma and other forms of skin cancer?

A. They are molecularly different, but there is a behavioral link, as excessive sun exposure is a risk factor in all skin cancers.

Q. I was treated with immunotherapy for my melanoma, and it has now recurred. Can I be treated with another immunotherapy?

A. More than likely, yes. Different types of immunotherapy work differently. It may even be that the immunotherapy you were treated with initially may work. This is an area that is the subject of ongoing research.

Q. Basal cell and squamous cell cancers run in my family. What measures can I take to prevent my young children from getting skin cancer?

A.The number one recommendation is to avoid excess sun exposure. Getting a suntan or sunburn increases the risk of developing basal cell or squamous cell cancer, as well as melanoma. Make sure your children are protected with broad-spectrum sunscreens (reapplied every two hours), wide-brimmed hats, and sunglasses. As much as possible, they should seek shade during peak sun times between 10 a.m. and 4 p.m.

Q. My doctor referred me to a dermatologist for treatment of actinic keratoses. What are they, and can they lead to skin cancer?

A.These small, flaky pieces of skin look a little bit like a scab. They can appear on the forehead and other parts of the face, as well as the neck, hands, arms and chest— all areas exposed to the sun. You might be able to wash or rub them off, but they tend to come back in the same place. Actinic keratoses are common, and many cause no problem. However, some can develop into squamous cell cancer. If you have many actinic keratoses, you may be at a higher risk for not only squamous cell cancer but also basal cell cancer or even melanoma. The spots can be treated by a doctor with liquid nitrogen to remove the abnormal cells or with the use of topical medications to treat actinic keratoses involving a broad area. Always be sure to reduce your sun exposure and have yearly checkups.

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This booklet has been made possible by Bristol-Myers Squibb; and an independent educational grant from Merck & Co., Inc.

Last updated March 18, 2016

The information presented in this publication is provided for your general information only. It is not intended as medical advice and should not be relied upon as a substitute for consultations with qualified health professionals who are aware of your specific situation. We encourage you to take information and questions back to your individual health care provider as a way of creating a dialogue and partnership about your cancer and your treatment.

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