New drugs and new strategies have led to great progress in treating colorectal cancer.
In the United States, nearly 150,000 people are diagnosed with colorectal cancer every year. About 80 percent of people with colorectal cancer can be successfully treated with surgery.
After surgery, some people may still have cancer cells in the body that cannot be detected by tests. So doctors treat them with chemotherapy as well. The aim is to destroy any remaining tumor cells, decrease the chances of the cancer coming back and extend survival. Called adjuvant therapy, drugs given after surgery can reduce the risk of tumor cells spreading to other parts of the body (metastatic cancer).
Colorectal cancer metastasizes in about 20 percent of patients. For these people, chemotherapy or targeted treatments have been shown to be effective. (Unlike chemotherapy, targeted treatments are designed to spare healthy tissues and tend to cause less severe side effects.)
In the past, people with colorectal tumors that spread to the liver and lungs, for example, were not offered surgery. But now, with the development of new drugs that help control the cancer, some of these patients can benefit from surgery to remove metastatic tumors.
In another exciting advance, thanks to clinical trials, doctors are now finding the best treatment approach for each patient based on his or her tumor’s genetic makeup. The cells of colorectal cancer tumors have their own distinct gene patterns. As researchers learn more about these patterns, they are finding ways to predict how some tumors will respond to various treatments. This kind of information helps doctors as they make decisions about what treatments to recommend to extend survival and improve quality of life.
The standard treatment for colorectal cancer is often surgery to remove the section of colon that contains the tumor as well as nearby lymph nodes. (Lymph nodes are small organs located throughout the body that remove waste and fluids and help fight infection.) When a tumor is removed, doctors determine how likely it is that the cancer will return. In part, this depends on whether the tumor has passed through the wall of the colon or rectum or if tumor cells have spread to the lymph nodes. Once cancer cells reach the lymph nodes, they may spread to form new tumors in other parts of the body.
Chemotherapy given after surgery can greatly reduce the chance of colorectal cancer spreading. For patients who have had surgery and whose cancer has not spread, the drugs used to reduce the chance of metastasis are oxaliplatin (Eloxatin and others) and 5-fluorouracil (5-FU) or capecitabine (Xeloda and others), an oral form of 5-FU. For people whose colorectal cancer has already spread to the liver or lungs, for example, doctors often treat with chemotherapy alone. In some cases, surgery may benefit patients with metastatic colorectal cancer, especially if chemotherapy has shrunk their tumors.
The medications used to treat metastatic colorectal cancer are 5-FU plus folinic acid (leucovorin) or levoleucovorin (Fusilev), capecitabine, oxaliplatin and irinotecan (Camptosar and others). These drugs are combined in various ways to make them more effective. The most common drug combinations are called FOLFOX and FOLFIRI. Although the dose and schedule vary, doctors give these treatments in cycles, each lasting two to four weeks. Treatment cycles are followed by a rest period to give the body time to recover from any side effects.
Targeted treatments focus on specific cell mechanisms thought to be important for the growth and survival of tumor cells. They work in different ways to destroy cancer cells:
Bevacizumab (Avastin) cuts off the blood and oxygen supplies that tumors need to grow.
Cetuximab (Erbitux) and panitumumab (Vectibix) block certain kinds of receptors that act as small antennas on the surface of colorectal cancer cells. When substances called growth factors attach to these receptors, they signal the cancer cells to grow and multiply. By blocking the receptors, these drugs prevent the growth factors from attaching and the cancer cells from growing into tumors. Cetuximab and panitumumab are part of a class of drugs known as EGFR inhibitors.
Regorafenib (Stivarga) targets kinase proteins, substances that send important signals to the cell’s control center. Some of the kinases help cells grow, while others help form new blood vessels that feed a growing tumor. Regorafenib, which comes in pill form, is designed to help stop the growth of tumors by blocking these kinase proteins.
Personalizing Treatment: The Role of KRAS
Each tumor has its own biological makeup, based on the genes found in its cells. An important area of cancer research is understanding the biology of tumors and their genes. With this information, doctors can learn whether a particular tumor is likely to respond—and to which treatment. That helps doctors choose the right treatment for each person’s tumor. This approach is much more effective than using the same treatment for everyone. Some treatments don’t work for certain types of tumors.
To better understand what type of tumor a patient has, doctors look for tumor “markers” in the cell’s genes. Markers can predict whether a given treatment will be effective against a tumor or whether there is a high risk of the tumor coming back.
A key tumor marker that has been found in colorectal cancer is the KRAS gene. Forty percent of people with colorectal cancer have a mutation (change) in the KRAS gene. Through clinical trials, researchers have learned that these patients do not benefit from treatment with EGFR inhibitors. However, they do benefit from chemotherapy.
The other 60 percent of people with colorectal cancer have what is known as the KRAS wild-type gene––the normal, unchanged form of the KRAS gene. These patients do tend to benefit from treatment with EGFR inhibitors.
Knowing whether you have a KRAS mutation or the KRAS wild-type gene is important to your health care team in deciding the best treatment for your specific type of cancer. Because people with KRAS mutations will not benefit from EGFR inhibitors, they need not spend valuable time taking those drugs and experiencing their side effects. Instead, they can use other treatments that will be more helpful to them––or consider taking part in clinical trials.
Because tumor markers are such an important step on the road toward personalized medicine, researchers conduct many clinical trials on them. They are looking for new treatments that will work for people with KRAS mutations. They are also continuing to study people with the KRAS wild-type gene to learn more about the medicines that will benefit them.
To effectively treat any cancer, doctors must be able to give patients their full dose of medications, on schedule. But side effects of chemotherapy and targeted treatments can interfere with treatment. That is why it is so important to prevent side effects, or to treat them promptly if they do develop. If you are experiencing any side effects, you can and should seek help. If your doctor doesn’t ask you about side effects, be sure to bring them up.
Here is a list of common side effects and ways they can be prevented and managed:
Nausea and vomiting are common concerns when it comes to chemotherapy. But the management of these symptoms has improved so much that most patients are able to avoid them. Doctors can prescribe a number of different drugs to prevent and reduce nausea and vomiting, including ondansetron (Zofran and others), granisetron and dolasetron (Anzemet). The steroid dexamethasone is also sometimes used, as is aprepitant (Emend).
Infections can result when the level of white blood cells drops due to chemotherapy. To raise the level of these blood cells, doctors sometimes prescribe medications such as filgrastim (Neupogen) or pegfilgrastim (Neulasta).
Anemia, caused by a lowered level of red blood cells, often occurs in patients with colorectal cancer who develop blood in the stool. Fatigue (an extreme tiredness that isn’t usually eased by sleep) is a main symptom of anemia. Depending on the cause, anemia treatment may include eating more iron-rich foods such as dark green, leafy vegetables; sweet potatoes; beans; meat and fish; or enriched bread, cereal or pasta. Ask your health care team which foods would be best for you. In some cases, doctors treat anemia with blood transfusions or drugs that help the body to make more red blood cells.
Blood clots may affect some cancer patients. This serious side effect occurs when a solid mass of blood forms and lodges in a blood vessel or in the heart, for example. Blood thinners such as warfarin (Coumadin and others) and drugs called LMWHs (low-molecular-weight heparins) effectively treat blood clots. For patients in the hospital who have had cancer surgery, doctors also use a mechanical cuff to prevent blood clots. The cuff is placed on the legs. It gently squeezes every few minutes to help keep blood flowing.
Mucositis (sores inside the mouth and on the lining of the throat and digestive tract) can result from radiation treatments and from some types of chemotherapy. Mucositis can be a serious problem because it can cause pain and infections, making it difficult to eat, drink and swallow. Once treatment ends, mouth sores do disappear. But before they fade, it’s important to work closely with your health care team to manage this side effect with good oral care and prescription products such as Gelclair or “miracle mouthwash” (sometimes called “magic mouthwash”).
Skin rash and other skin and nail conditions often result from the use of targeted treatments such as cetuximab and panitumumab. The symptoms are actually a sign that these drugs are working. If you are taking these medications or other EGFR inhibitors, talk with your health care team about the possible side effects and various ways to treat them.
Neuropathy (nerve damage) from chemotherapy such as oxaliplatin can lead to numbness or tingling in the hands and feet. Some people experience this symptom for months or even years. There is no sure way to prevent neuropathy, and doctors are still looking for treatments that work. Gabapentin (Neurontin and others) is often used to relieve the pain of neuropathy. A lot of research is being done in this area.
Talk with your doctor if you are interested in getting into a clinical trial studying neuropathy. In the meantime, avoid drinking alcohol, which can damage nerves. Wear sneakers or shoes with “rocker bottoms” that allow the feet to roll while walking and can relieve some of the pressure on the soles. And use hand tools, kitchen utensils and even toothbrushes and pens with wider grips that make them easier to hold. It’s very important to talk with your doctor about nerve symptoms you experience so that he or she can adjust the dose or stop oxaliplatin if needed.
Pain can greatly affect your quality of life––your daily activities, eating habits, ability to get a good night’s sleep and even your outlook and how you interact with others. Controlling different types of pain may require different approaches, which is why it is so important for members of your health care team to understand the cause of your pain and for you to have good communication with them.
Another part of managing side effects is choosing the best diet and activity level for your health. It’s important to talk with your medical team, both during and after treatment, about which lifestyle changes may benefit you. Find out if your doctor has a registered dietitian (RD) on staff or can recommend one. RDs are experts in diet and nutrition and can advise you about eating right.
The tips here should serve as a general guideline for healthy choices and offer ways to prevent or reduce some treatment side effects:
Maintain your weight. Small meals eaten throughout the day are an easy way to take in calories and protein.
Choose nutrient-dense foods, preferably lower in fat. Chemotherapy and cancer itself can rob the body of nutrients. One way to manage this loss is by eating as much protein as possible. Lean red meat, chicken, turkey, fish, low-fat dairy, soy products and peanut butter are all good examples of high-protein foods. Beans, lentils and the grain quinoa are excellent sources of protein too.
Choose fiber-dense foods. Especially if you are feeling constipated, high-fiber foods such as vegetables, fruits and grains are healthy choices.
Avoid certain foods. If you are experiencing nausea and vomiting, it’s best to avoid food with offending odors, as well as overly sweet, greasy, fried or highly seasoned food. Meals that can be eaten cold or at room temperature are often more easily tolerated.
Nibble on dry crackers or toast. These bland foods are easy on the stomach. And having a little something in your stomach when you take medication or before you get up from sitting or lying down can help ease nausea.
If you have mouth sores, choose soft, moist foods that are easy to chew and swallow. Any rough-textured foods like chips or crackers could be irritating. Also avoid foods that are acidic, tart or spicy.
If it’s difficult to swallow, try pureeing your food. Consider using a supplemental drink like Ensure or fixing your own smoothies.
If you have diarrhea, avoid sweetened foods and alcohol. Fiber-dense foods can also help form solid stools.
Drink plenty of fluids. This becomes especially important if you are experiencing diarrhea. Be sure to include electrolytes so that you do not get dehydrated. Electrolytes are the body’s salts, and they must stay in balance in order for cells to work properly. Ask your doctor if electrolyte-rich sports drinks such as Gatorade would be helpful to you.
If possible, engage in at least 30 minutes of physical activity each day. There are many benefits, including easing constipation. The activity can be anything you enjoy doing: walking, swimming, riding a bike or playing a sport such as golf or tennis. Of course, during cancer treatment, you may need to have a lighter schedule of activity, especially if you feel fatigued. That is fine; go at your own pace. You will find that staying as active as possible can help you regain your energy. Try to stay active for at least 10 minutes and then build from there.
Q. I was recently diagnosed with colon cancer and will have surgery and then a colostomy. I’m grateful that surgery is an option, but I’m struggling with the idea of having a colostomy. Any advice?
A. Adjusting to a cancer diagnosis can be challenging enough; adjusting to the physical challenges that might come with it can seem overwhelming. It’s completely normal to wonder how you will manage. Seeking out information and support will help you to understand what to expect and how best to cope with change.
A colostomy surgically creates a “stoma,” or small opening, in the lower abdomen through which stool can exit the body. Usually, the waste is captured in a small bag that is worn on the body and can be easily disposed of. Although this procedure will have an obvious impact on your daily routines, keep in mind that you will still be able to do all the things you enjoy, including physical activities such as sports or gardening, and continue to live a full life with a colostomy.
An enterostomal therapy nurse, who specializes in ostomy care and rehabilitation, can be especially helpful to you. Speaking with an oncology social worker or joining a support group where you can discuss your concerns and learn how others have coped and adjusted also can be very useful.
You can find additional information and support through the United Ostomy Associations of America, which provides many resources. (See sidebar for contact information.)
Remember that with any change comes loss. Give yourself time to adjust as you move into this next stage of your life.
Q. What are multidisciplinary health care teams, and why are they important?
A. Sometimes, it takes many specialties, or “disciplines,” within medicine to evaluate an illness or symptom and manage it. This is especially true with cancer, where caring for patients is a complex process that requires a team approach. For people with colorectal cancer, a number of different types of medical issues often arise, with each one best managed by a specialist. Patients may need a surgeon, medical oncologist, radiation oncologist, nurse, pain management expert and registered dietitian, for example. One member of the team–– usually the medical oncologist––coordinates the care a patient receives from various members of the team.
Many people also need help coping with the emotional or practical concerns that come up during treatment. Oncology social workers, counselors, financial specialists and other non-medical professionals are available to help. CancerCare can help you find resources in each of these areas. Call us at 800-813-HOPE (4673) or visit www.cancercare.org.