Skin cancer is the most common cancer in the United States.
While one in five Americans will develop skin cancer over the course of their lifetime, skin cancer can usually be treated with a relatively simple surgery, if found early. Basal cell carcinoma (BCC) is the most common type of skin cancer, followed by squamous cell carcinoma (SCC) and melanoma.
Basal Cell and Squamous Cell Carcinomas
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 and affects 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 Carcinoma
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; in January 2012, it was 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 taken in capsule form; it is designed to target the specific cell mechanisms that are important for the growth and survival of tumor cells.
People with a rare disease 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.
In July 2015, the FDA approved the targeted treatment 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, given intravenously, 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 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 for 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 can be given orally or intravenously; they can 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.
Treatment Approaches for Melanoma
Melanoma is the most serious type of skin cancer. It develops in the cells that produce melanin, the pigment that gives color to skin, hair, and eyes. 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.
In some cases, the melanoma can recur after the initial treatment and can spread (metastasize). In the past few years, a number of drugs to treat metastatic (advanced) 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 by blocking their ability to grow, divide, and spread (targeted treatments).
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. As there are a number of treatment options for advanced 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 in the Treatment of Advanced Melanoma
Immunotherapy is treatment that uses certain parts of the immune system to fight illnesses, including cancer. There are several immunotherapies approved to treat advanced melanoma:
- Interferon (Intron A, Sylatron). In 1995, the FDA approved interferon as an adjuvant (post-surgery) therapy for patients whose advanced melanoma tumors were removed surgically. The use of interferon in these circumstances may stop the growth and spread of any remaining melanoma cells.
- Aldesleukin (interleukin-2, Proleukin). Since the late 1990s, aldesleukin has been approved as a standard treatment for metastatic (advanced) melanoma. Given through a vein, aldesleukin helps the body’s immune system shrink and destroy tumors more effectively. Aldesleukin is not used as commonly today as it was in the past, 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.
- embrolizumab (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 (Opdivo). Like pembrolizumab, nivolumab works by blocking the PD-1 pathway; it is also given through a vein. Nivolumab was approved for treatment of metastatic melanoma in December 2014.
Both pembrolizumab and nivolumab are intended for patients who have been previously treated with ipilimumab or for use after treatment with ipilimumab and a BRAF inhibitor (used in treatment of melanoma patients whose tumors express a gene mutation called BRAF V600).
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.
Also in October 2015, the FDA approved talimogene laherparepvec (Imlygic) for treatment of advanced melanoma of the skin and lymph nodes that cannot be removed completely by surgery. Talimogene laherparepvec is an oncolytic virotherapy (a virus that attacks and breaks down cancer cells, but does not effect normal cells); it is injected directly into the melanoma lesions, where it causes cancer cells to rupture and die. Talimogene also appears to improve the immune system’s response to cancer.
Targeted Treatments in the Treatment of Advanced Melanoma
Targeted treatments are designed to inhibit specific cell mechanisms important for the growth and survival of tumor cells. Patients who may benefit from these targeted treatments have specific DNA changes, called driver mutations, that allow cancers to develop and grow.
Four targeted treatments have been approved by the FDA for the treatment of melanoma that have these DNA changes:
- Vemurafenib (Zelboraf). In August 2011, the FDA approved vemurafenib, a drug that inhibits the “signal transduction” pathway in patients that have a BRAF gene mutation. Vemurafenib can help slow or stop the spread of melanoma cells and can shrink tumors in areas of the body such as the liver, bowel, and bone.
- Dabrafenib (Tafinlar). In May 2013, the FDA approved dabrafenib, which targets the BRAF gene mutation in the same way vemurafenib does.
- Trametinib (Mekinist). In May 2013, Trametinib was approved as a single agent to treat patients with metastatic melanoma that cannot be removed by surgery. In January 2014, the FDA approval was expanded to include treatment in combination with dabrafenib. Trametinib blocks a protein called MEK, which is “switched on” by BRAF.
- Cobimetinib (Cotellic). In November 2015, the FDA approved cobimetinib for the treatment of patients with unresectable or metastatic melanoma with a BRAF V600E or V600K mutation, in combination with vemurafenib.
All cancer treatments can cause side effects. It’s important that you report any side effects that 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 allow you to stick with your treatment plan. 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 Vismodegib and Sonidegib, in Treatment of BCC
Many patients remain on a targeted treatment for months or even years, and they are generally considered very well-tolerated. However, there are side effects that patients should be aware of:
- Muscle cramps and spasms. A significant number of people on a targeted treatment 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 muscle stretching 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. Some people on a targeted treatment develop a metallic or cardboard-like taste in their mouth. Your doctor or a registered dietician can suggest a specific diet to help ease this side effect.
- Thinning hair. Targeted treatments 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 Radiation, in Treatment of BCC and SCC
Changes to the skin are the most common side effects of radiation; these changes can include dryness, swelling, peeling, redness, and blistering. To help prevent these side effects, ask your radiation therapist if it is appropriate to use corticosteroid cream to the area being treated.
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 Cetuximab, in Treatment of SCC
- Rash. Many people who take cetuximab get an itchy rash on their face and upper body, and sometimes on their scalp. 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 and waxing.
Side Effects of Targeted Therapy
Targeted therapy drugs don’t have the same effect on the body as do chemotherapy drugs, but they can still cause side effects. Common side effects of targeted therapy include diarrhea, liver problems (such as hepatitis and elevated liver enzymes), proteinuria (high levels of protein in the urine), problems with blood clotting and wound healing, and high blood pressure.
Side Effects of Immunotherapy
Immunotherapy travels through the bloodstream, helping to prompt an immune response. Because it may attack healthy cells as well as cancer cells, certain side effects may be experienced, including fatigue, decreased appetite, and digestive tract symptoms. The management of these potential side effects is discussed later in the next section of this booklet.
Managing General Side Effects
There are certain side effects that may occur across different treatment approaches. Following are tips for managing these side effects. Your health care team may have additional guidance for your specific treatment type.
Digestive Tract Symptoms
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.
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.
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, your doctor may delay or lower the dose of the drug, as long as it does not make the treatment less effective. If you are experiencing 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.
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.
There are a number of options for pain relief, including prescription and over-the-counter medications. It’s important to talk to a member of your health care team before taking any over-the counter medication, to determine if they are safe and will not interfere with your treatments.
The Importance of Communicating With 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 dietician 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, consider working 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. There is a high likelihood of a successful outcome if the melanoma is recognized and treated at an early stage.
- 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. 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 area is the subject of ongoing research. On a related topic, it is important to note that there is no known reason to undergo multiple treatment types at the same time, and that approach has never been investigated.
Q. Are melanomas genetic?
A. Most melanomas occur in patients where no family or genetic link can be found. However, there is a rare form of melanoma that arises in childhood, without sun exposure, which is thought to be genetic. In addition, it is important to provide your doctor with your family’s cancer history, as melanoma can be caused by gene changes found in families; these changes also have risks for breast, colon, and pancreatic cancers. For melanomas related to sun exposure, having a close relative with melanoma is a risk factor, but it’s not clear if the link is genetic or behavioral. Annual screenings for melanoma are recommended if you have a close relative with melanoma.