Classification: Tyrosine Kinase Inhibitor
About Regorafenib (Stivarga®)
Regorafenib is a type of targeted therapy called a tyrosine kinase inhibitor. A kinase is an enzyme that promotes cell growth. There are many types of kinases, which control different phases of cell growth. Regorafenib targets several different receptors, which, in turn, blocks tumor growth and angiogenesis (the development of a blood supply to the tumor).
How to Take Regorafenib
Regorafenib comes as 40 mg tablets, four tablets are to be taken at the same time once a day for a total daily dose of 160 mg for 21 days out of a 28 day cycle (3 weeks on, 1 week off). Your care team may adjust your dose based on your individual treatment plan. Swallow the tablet whole after a low-fat breakfast (containing less than 600 calories and less than 30% fat). Do not break, chew or crush the tablets. If you miss a dose, take it as soon as you remember on that day. Do not take two doses in one day to make up a missed dose.
Examples of a low-fat breakfast includes:
- 2 slices of white toast with 1 tablespoon of low-fat margarine and 1 tablespoon of jelly, and 8 ounces of skim milk (319 calories and 8.2 grams fat).
- 1 cup of cereal, 8 ounces of skim milk, 1 slice of toast with jelly, apple juice, and 1 cup of coffee or tea (520 calories and 2 grams fat).
It is important to make sure you are taking the correct amount of medication every time. Before every dose, check that what you are taking matches what you have been prescribed.
The blood levels of this medication can be affected by certain foods and medications, so they should be avoided. These include: grapefruit, grapefruit juice, ketoconazole, rifampin, carbamazepine, phenobarbital, phenytoin, St. John’s wort, and many anti-fungal medications. Be sure to tell your healthcare provider about all medications and supplements you take.
Storage and Handling
Store your medication in the original, labeled container at room temperature and in a dry location (unless otherwise directed by your pharmacist). This medication should not be stored in a pillbox. Do not remove the desiccant packet from the container, as this keeps the environment in the bottle dry. Keep containers out of reach of children and pets.
If a caregiver prepares your dose for you, they should consider wearing gloves or pour the pills directly from their container into the cap, a small cup, or directly into your hand. They should avoid touching the pills. They should always wash their hands before and after giving you the medication. Pregnant or nursing women should not prepare the dose for you. Ask your oncology team where to return any unused medication for disposal. Do not flush down the toilet or throw in the trash.
Where do I get this medication?
Regorafenib is available through select specialty pharmacies. Your oncology team will work with your prescription drug plan to identify an in-network specialty pharmacy for distribution of this medication and shipment directly to your home.
This medication may be covered under your prescription drug plan. Patient assistance may be available to qualifying individuals without prescription drug coverage. Co-pay cards, which reduce the patient co-pay responsibility for eligible commercially (non-government sponsored) insured patients, are also available. Your care team can help you find these resources, if they are available.
Possible Side Effects of Regorafenib
There are a number of things you can do to manage the side effects of regorafenib. Talk to your care team about these recommendations. They can help you decide what will work best for you. These are some of the most common or important side effects:
High Blood Pressure
This medication can cause high blood pressure (hypertension). Patients should have their blood pressure checked regularly during therapy. Any hypertension should be treated appropriately. If hypertension cannot be controlled, the medication may be stopped. Report any headaches, vision changes or dizziness to your oncology care team.
Hand Foot Syndrome
Hand foot syndrome (HFS) is a skin reaction that appears on the palms of the hands and/or the soles of the feet, as a result of certain chemotherapy agents being absorbed by the skin cells. HFS can begin as a mild tingling, numbness, pins-and-needles feeling, redness or pain or swelling of the hands and/or feet. This can then progress to painful swelling, blistering or peeling skin that can interfere with your ability to do normal activities. Be sure to let your oncology team know right away if you notice these symptoms, as they may need to adjust the chemotherapy dose or take a break to allow the skin to heal. Some tips to help prevent HFS include:
- Keep hands and feet clean and dry.
- Avoid tight shoes or socks.
- Avoid activities that put pressure on the palms or soles for 1 week after treatment.
- Apply an alcohol-free moisturizer liberally and often. (Avoid moisturizers with perfumes or scents)
- Avoid very hot water for baths and showers.
Skin, Hair & Nail Changes
Some patients may develop a rash, very dry, or itchy skin. Use an alcohol free moisturizer on your skin and lips; avoid moisturizers with perfumes or scents. Your doctor or nurse can recommend a topical medication if itching is bothersome. Your nails may become dark, brittle or fall off. If your skin does crack or bleed or you lose a nail, be sure to keep the area clean to avoid infection. While receiving this medication the hair on your head may become curly, fine or brittle. This tends to resolve once treatment is stopped.
Be sure to notify your healthcare provider of any rash that develops, as this can be a reaction and can become severe. They can give you more tips on caring for your skin, hair and nails.
Low Red Blood Cell Count (Anemia)
Your red blood cells are responsible for carrying oxygen to the tissues in your body. When the red cell count is low, you may feel tired or weak. You should let your oncology care team know if you experience any shortness of breath, difficulty breathing or pain in your chest. If the count gets too low, you may receive a blood transfusion.
Low Platelet Count (Thrombocytopenia)
Platelets help your blood clot, so when the count is low you are at a higher risk of bleeding. Let your oncology care team know if you have any excess bruising or bleeding, including nose bleeds, bleeding gums or blood in your urine or stool. If the platelet count becomes too low, you may receive a transfusion of platelets.
- Do not use a razor (an electric razor is fine).
- Avoid contact sports and activities that can result in injury or bleeding.
- Do not take aspirin (salicylic acid), non-steroidal, anti-inflammatory medications (NSAIDs) such as Motrin/Advil (ibuprofen), Aleve (naproxen), Celebrex (celecoxib) etc. as these can all increase the risk of bleeding. Please consult with your healthcare team regarding use of these agents and all over the counter medications/supplements while on therapy.
- Do not floss or use toothpicks and use a soft-bristle toothbrush to brush your teeth.
Fatigue is very common during cancer treatment and is an overwhelming feeling of exhaustion that is not usually relieved by rest. While on cancer treatment, and for a period after, you may need to adjust your schedule to manage fatigue. Plan times to rest during the day and conserve energy for more important activities. Exercise can help combat fatigue; a simple daily walk with a friend can help. Talk to your healthcare team for helpful tips on dealing with this side effect.
Mouth Ulcers (Mucositis)
Certain cancer treatments can cause sores or soreness in your mouth and/or throat. Notify your oncology care team if your mouth, tongue, inside of your cheek or throat becomes white, ulcerated or painful. Performing regular mouth care can help prevent or manage mouth sores. If mouth sores become painful, your doctor or nurse can recommend a pain reliever.
- Brush with a soft-bristle toothbrush or cotton swab twice a day.
- Avoid mouthwashes that contain alcohol. A baking soda and/or salt with warm water mouth rinse (2 level teaspoons of baking soda or 1 level teaspoon of salt in an eight ounce glass of warm water) is recommended 4 times daily.
- If your mouth becomes dry, eat moist foods, drink plenty of fluids (6-8 glasses), and suck on sugarless hard candy.
- Avoid smoking and chewing tobacco, drinking alcoholic beverages and citrus juices.
Your oncology care team can recommend medications to relieve diarrhea. Also, try eating low-fiber, bland foods, such as white rice and boiled or baked chicken. Avoid raw fruits, vegetables, whole grain breads, cereals and seeds. Soluble fiber is found in some foods and absorbs fluid, which can help relieve diarrhea. Foods high in soluble fiber include: applesauce, bananas (ripe), canned fruit, orange sections, boiled potatoes, white rice, products made with white flour, oatmeal, cream of rice, cream of wheat, and farina. Drink 8-10 glasses on non-alcoholic, un-caffeinated fluid a day to prevent dehydration.
This medication can cause changes to your voice including hoarseness.
You should let your care team know right away if you have a fever (temperature greater than 100.4), sore throat or cold, shortness of breath, cough, burning with urination, or a sore that doesn't heal. The most common infection related to this medication is a urinary tract infection. Symptoms of urinary tract infection include frequency, urgency and burning with urination.
Decrease in Appetite
Nutrition is an important part of your care. Cancer treatment can affect your appetite and, in some cases, the side effects of treatment can make eating difficult. Ask your oncology care team about nutritional counseling services at your treatment center to help with food choices.
- Try to eat five or six small meals or snacks throughout the day, instead of 3 larger meals.
- If you are not eating enough, nutritional supplements may help.
- You may experience a metallic taste or find that food has no taste at all. You may dislike foods or beverages that you liked before receiving cancer treatment. These symptoms can last for several months or longer after treatment ends.
- Avoid any food that you think smells or tastes bad. If red meat is a problem, eat chicken, turkey, eggs, dairy products and fish without a strong smell. Sometimes cold food has less of an odor.
- Add extra flavor to meat or fish by marinating it in sweet juices, sweet and sour sauce or dressings. Use seasonings like basil, oregano or rosemary to add flavor. Bacon, ham and onion can add flavor to vegetables.
This medication can lead to slower or incomplete wound healing, such as a surgical wound not healing or staying closed. Therefore, it is recommended that the medication be discontinued 2 weeks prior to any surgery. In addition, any surgical incision should be fully healed prior to starting or restarting the medication. If you have a surgical wound that has not healed or begins to have signs of infection (redness, swelling, warmth), report this to your healthcare team.
This medication can cause an increase in the amounts of protein in your urine. Your healthcare team will monitor your kidney function and protein in your urine throughout treatment with this medication.
This medication can cause liver toxicity, which your doctor may monitor for using blood tests called liver function tests. Notify your healthcare provider if you notice yellowing of the skin or eyes, your urine appears dark or brown or pain in your abdomen, as these can be signs of liver toxicity.
Less common, but important side effects can include:
- Hemorrhage (Bleeding): Serious bleeding has also occurred in patients treated with this medication. People who have a history of serious bleeding should not take this medication. If you take aspirin, non-steroidal anti-inflammatory medications (i.e. Motrin, ibuprofen, naproxen) or other medication that interferes with blood clotting, let your healthcare provider know. Signs of bleeding can include: blood in the stool or dark, tarry stools, coughing up or vomiting blood or vomit that looks like coffee grounds. While some bleeding, such as a nosebleed, may not seem like much of a concern, you should notify your healthcare team right away if you develop bleeding of any sort.
- GI Tear or Fistula: This medication can cause a tear in the intestinal wall, also called a gastrointestinal perforation, or a fistula (whole connecting two parts of your GI tract). Signs of this can include: new or worsening pain in the abdomen, new abdominal swelling, chills, fever, constipation, nausea or vomiting. If you experience any of these, contact your healthcare provider immediately or go to the emergency room.
- Posterior Reversible Encephalopathy Syndrome (PRES): In rare cases this medication has caused a neurological disorder called posterior reversible encephalopathy syndrome (PRES), also called reversible posterior leukoencephalopathy (RPLS). Symptoms of PRES/RPLS include headache, seizure, lethargy, confusion, blindness and other visual and neurological disturbances. Report any of these symptoms to your healthcare team immediately.
- Heart Attack: In studies, patients experienced heart attack and chest pain. If you experience symptoms of these problems, you should contact your healthcare provider immediately or go to an emergency room. Symptoms can include: chest pain or pressure, pain in your arm, back, neck or jaw, shortness of breath or dizziness.
Exposure of an unborn child to this medication could cause birth defects, so you should not become pregnant or father a child while on this medication. Effective birth control is necessary during treatment and for at least 2 months after treatment. Even if your menstrual cycle stops or you believe you are not producing sperm, you could still be fertile and conceive. You should consult with your healthcare team before breastfeeding while receiving this medication.