Generic name: Regorafenib

Stivarga^® is the trade name for the generic chemotherapy drug regorafenib. In some cases, health care professionals may use the generic name regorafenib when referring to the trade name Stivarga^®.

Drug type: Stivarga^® is a targeted therapy. It is an oral receptor tyrosine kinase inhibitor - (For more detail, see "How this drug works," below.)

What Stivarga Is Used For:

• For the treatment of colorectal cancer.
• For the treatment of hepatocellular carcinoma (HCC) after prior treatment with sorafenib.

Note: If a drug has been approved for one use, physicians may elect to use this same drug for other problems if they believe it may be helpful.

How Stivarga Is Given:

• Stivarga^® is a pill, taken by mouth, once daily. Take with a low-fat (less than 30% fat) breakfast. Examples of a low-fat breakfast include:

1. 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 of fat), or
2. 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 of fat).

• Take Stivarga^® exactly as prescribed.
• Take Stivarga^® at the same time every day.
• Swallow Stivarga^® tablets whole. Do not crush or dissolve.
• Do not change your dose or stop Stivarga^® unless your health care provider tells you to.
• If you miss a dose, take it as soon as you remember. If it is too close to your next dose (within 12 hours), just take your next dose at your regular time.
• Do not take more than 1 dose of Stivarga^® at one time. Call your health care provider right away if you take too much.
• The amount of Stivarga^® that you will receive depends on many factors, your general health or other health problems, and the type of cancer or condition being treated. Your doctor will determine your dose and schedule.

Side Effects:

Important things to remember about the side effects of Stivarga^®:

• Most people do not experience all of the side effects listed.
• Side effects are often predictable in terms of their onset and duration.
• Side effects are almost always reversible and will go away after treatment is complete.
• There are many options to help minimize or prevent side effects.
• There is no relationship between the presence or severity of side effects and the effectiveness of the medication.

The following side effects are common (occurring in greater than 30%) for patients taking Stivarga^®:

• Anemia
• Increased liver enzymes (AST, ALT)
• Fatigue
• Protein in the urine
• Low calcium
• Low phosphorous
• Low white blood cells
• Decreased appetite
• Increased enzymes produced by the pancreas (lipase & amylase)
• High bilirubin in the blood
• Hand-foot syndrome (redness, swelling, pain, skin changes on the palms and feet)
• Diarrhea
• Low platelets
• Mouth sores/inflammation
• Weight loss
• Infection
• High blood pressure
• Voice disorder (Dysphonia)
• Low sodium
• Nausea

These side effects are less common side effects (occurring in about 10-29%) of patients receiving Stivarga^®:

• Pain
• Fever
• Rash
• Low potassium
• INR increased (decreased blood clotting)
• Increased bleeding
• Headache
• Alopecia

A serious, but very uncommon side effect of Stivarga^® is liver problems. Sometimes medications are not safe when you take them with certain other medications. Taking them together may cause bad side effects. This is one of those medications. Be sure to discuss with your provider about all the medications you take and do not start anything new without prior approval. This includes those that are over the counter and herbal as well.

Not all side effects are listed above. Some that are rare (occurring in less than 10% of patients) are not listed here. However, you should always inform your health care provider if you experience any unusual symptoms.

When to contact your doctor or health care provider:

Contact your health care provider immediately, day or night, if you should experience any of the following symptoms:

• Fever of 100.4° F (38° or higher, chills)
• Signs of a very bad reaction (wheezing, chest tightness, fever, itching, bad cough, blue or grey skin color, seizures, or swelling or the face, lips, tongue or throat).
• Sudden change in eyesight, fast heartbeat, very bad headache, very bad dizziness or passing out.

Always inform your health care provider if you experience any unusual symptoms.

The following symptoms require medical attention, but are not an emergency. Contact your health care provider within 24 hours of noticing any of the following:

• Diarrhea (4-6 episodes in a 24-hour period).
• Nausea (interferes with ability to eat and unrelieved with prescribed medication).
• Vomiting (vomiting more than 4-5 times in a 24 hour period).
• Unable to eat or drink for 24 hours or have signs of dehydration: tiredness, thirst, dry mouth, dark and decrease amount of urine, or dizziness.

• Skin or the whites of your eyes turn yellow
• Urine turns dark or brown (tea color)
• Decreased appetite
• Pain on the right side of your stomach
• Bleed or bruise more easily than normal
• Skin changes (rash, acne, itching, blisters, peeling, redness or swelling)
• Increase in blood pressure
• Feeling very tired or weak (unable to carry on self-care activities)
• Big weight gain or loss
• Black or tarry stools, or blood in your stools
• Blood in the urine
• Signs of infection (very bad sore throat, ear or sinus pain, cough, more sputum or change in color of sputum, pain with passing urine, mouth sores, wound that will not heal or anal itching or pain).

Always inform your health care provider if you experience any unusual symptoms.

Precautions:

• Before starting Stivarga^® treatment, make sure you tell your doctor about any other medications you are taking (including prescription, over-the-counter, vitamins, herbal remedies, etc.). Do not take anything new without discussing with your provider first. This is very important as other medications, etc. may interact with Stivarga^®.
• Do not receive any kind of immunization or vaccination without your doctor's approval while taking Stivarga^®.
• Inform your health care professional if you are pregnant or may be pregnant prior to starting this treatment. Pregnancy category D (Stivarga ^® may be hazardous to the fetus. Women who are pregnant or become pregnant must be advised of the potential hazard to the fetus.)
• For both men and women: Do not conceive a child (get pregnant) while taking Stivarga^®. Barrier methods of contraception, such as condoms, are recommended during therapy and for at least 2 months following treatment. Discuss with your doctor when you may safely become pregnant or conceive a child after therapy.
• Do not breast feed while taking this medication.
• You should not drink grapefruit juice or eat grapefruit during your treatment with Stivarga^®. It may make the amount of Stivarga^® in your blood increase to a harmful level.
• If you are taking a blood thinner, have your blood levels checked as prescribed.
• Have your blood pressure checked often.

Self-Care Tips:

• Drink at least two to three quarts of fluid every 24 hours, unless you are instructed otherwise.
• You may be at risk of infection so try to avoid crowds or people with colds, and report fever or any other signs of infection immediately to your healthcare provider.
• Wash your hands often.
• Ask your doctor or nurse before scheduling dental appointments or procedures.
• Use an electric razor and a soft toothbrush to minimize bleeding.
• Avoid contact sports or activities that could cause injury.

• If you should experience nausea, take anti-nausea medications as prescribed by your doctor, and eat small frequent meals. Sucking on lozenges and chewing gum may also help.
• Avoid sun exposure. Wear SPF 15 (or higher) sun block and protective clothing.
• In general, drinking alcoholic beverages should be avoided completely. You should discuss this with your doctor.
• Get plenty of rest.
• Maintain good nutrition.
• Keep your mouth clean with baking soda and salt rinses. You can mix 1/2 to 1 tsp. of baking soda and/or 1/2 to 1 tsp. salt in 8 ounces of water, and use as a mouthwash, to avoid or decrease the severity of mouth sores.

• Stivarga^® can cause tiredness, weakness or blurred vision. If you have any of these symptoms, use caution when driving a car, using machinery, or anything that requires you to be alert.
• If you experience symptoms or side effects, be sure to discuss them with your health care team. They can prescribe medications and/or offer other suggestions that are effective in managing such problems.

Monitoring and Testing:

You will be checked regularly by your health care professional while you are taking Stivarga^®. Testing may include: electrolytes, complete blood counts, liver function test, and blood pressure to monitor side effects and check your response to therapy. If you are on warfarin (Coumadin) your blood INR may be monitored more frequently.

How Stivarga Works:

Targeted therapy is the result of about 100 years of research dedicated to understanding the differences between cancer cells and normal cells. To date, cancer treatment has focused primarily on killing rapidly dividing cells because one feature of cancer cells is that they divide rapidly. Unfortunately, some of our normal cells divide rapidly too, causing multiple side effects.

Targeted therapy is about identifying other features of cancer cells. Scientists look for specific differences in the cancer cells and the normal cells. This information is used to create a targeted therapy to attack the cancer cells without damaging the normal cells, thus leading to fewer side effects. Each type of targeted therapy works a little bit differently but all interfere with the ability of the cancer cell to grow, divide, repair and/or communicate with other cells.

There are different types of targeted therapies, defined in three broad categories. Some targeted therapies focus on the internal components and function of the cancer cell. The targeted therapies use small molecules that can get into the cell and disrupt the function of the cells, causing them to die. There are several types of targeted therapy that focus on the inner parts of the cells. Other targeted therapies target receptors that are on the outside of the cell. Therapies that target receptors are also known as monoclonal antibodies. Antiangiogenesis inhibitors target the blood vessels that supply oxygen to the cells, ultimately causing the cells to starve.

Stivarga^® is a targeted therapy that targets and binds to tyrosine kinase receptors and inhibits epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF), receptors on the surface of the cell. By binding to these receptors Stivarga^® blocks an important pathway that promotes cell division.

Research continues to identify which cancers may be best treated with targeted therapies and to identify additional targets for more types of cancer.

Note: We strongly encourage you to talk with your health care professional about your specific medical condition and treatments. The information contained in this website is meant to be helpful and educational, but is not a substitute for medical advice.

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