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As researchers have learned more about the gene and protein changes inside cells that cause them to become cancer cells, they have developed drugs that target some of these changes. These targeted drugs are different from standard chemotherapy (chemo) drugs. They tend to work better against kidney cancer than standard chemo drugs, and they often have different side effects.

When are targeted drugs used for kidney cancer?

Treating advanced kidney cancer

Targeted drugs are used mainly to treat advanced kidney cancer. One of these drugs is typically part of the first treatment for advanced cancers, often along with an immunotherapy drug.

Many different targeted drugs can be used to treat kidney cancer. If one doesn’t work, another can be tried. It’s not yet clear if one sequence of drugs is better than another. Studies are being done to help answer this.

Adjuvant therapy after surgery

The targeted drug sunitinib (Sutent) might also be an option as an adjuvant treatment after surgery to remove the kidney, to help lower the risk that the cancer will come back.

Targeted drugs used to treat kidney cancer

Most of the targeted drugs used to treat kidney cancer work by blocking proteins called tyrosine kinases inside cancer cells that normally help them grow, or that help them create new blood vessels that feed the tumor. Drugs that target these types of proteins are known as tyrosine kinase inhibitors, or TKIs.

Drugs that target tumor blood vessel growth (angiogenesis)

Sunitinib (Sutent)

Sunitinib acts by blocking both angiogenesis and several tyrosine kinases in cancer cells that are important for their growth and survival.

This drug is a pill taken daily, typically for 4 weeks on and 2 weeks off. Some doctors might recommend taking it 2 weeks on and 1 week off to reduce side effects.

Sunitinib can be used in people with advanced kidney cancer. It might also be an option after surgery in people with a high risk of their cancer returning, to help lower the risk that the cancer will come back, although an immunotherapy drug such as pembrolizumab (Keytruda) is more likely to be used in this situation instead.

The most common side effects of sunitinib are:

• Nausea
• Diarrhea
• Changes in skin or hair color
• Mouth sores
• Weakness
• Low white and red blood cell counts

Other possible effects include feeling tired, high blood pressure, heart problems, bleeding, hand-foot syndrome, and low thyroid hormone levels.

Pazopanib (Votrient)

Pazopanib blocks several tyrosine kinases involved in cancer cell growth, as well as the formation of new blood vessels in the tumor. This drug is a pill, typically taken once a day.

Common side effects of pazopanib include:

• High blood pressure
• Nausea
• Diarrhea
• Headaches
• Low blood cell counts
• Hair color change

It can cause abnormal liver function test results, but it rarely leads to severe liver damage that could be life threatening. Problems with bleeding, clotting, and wound healing can occur, as well.

In rare cases it can also cause a problem with the heart rhythm or even heart failure. If you are taking this drug, your doctor will monitor your heart with EKGs as well as check your blood tests for liver or other problems.

Cabozantinib (Cabometyx)

Cabozantinib blocks several tyrosine kinases that help cancer cells grow and survive, as well as some that help form new blood vessels in the tumor.

This drug can be used to treat advanced kidney cancer, either by itself or along with the immunotherapy drug nivolumab (Opdivo). It is taken as a pill, typically once a day.

Common side effects of cabozantinib include:

• Diarrhea
• Fatigue (feeling tired)
• Nausea and vomiting
• Poor appetite and weight loss
• High blood pressure
• Hand-foot syndrome
• Constipation

Less common but more serious side effects can include serious bleeding, blood clots, very high blood pressure, severe diarrhea, and holes forming in the intestines.

Lenvatinib (Lenvima)

Lenvatinib is a tyrosine kinase inhibitor that helps block new blood vessels from forming in the tumor, as well as targeting some of the proteins in cancer cells that normally help them grow.

This drug can be used along with the immunotherapy drug pembrolizumab in people with advanced kidney cancer. It can also be used with the targeted drug everolimus (see below). Lenvatinib is a capsule typically taken once a day.

Common side effects of lenvatinib include:

• Diarrhea
• Fatigue
• Joint or muscle pain
• Loss of appetite
• Nausea and vomiting
• Mouth sores
• Weight loss
• High blood pressure
• Swelling in the arms or legs

Less common but more serious side effects can include serious bleeding, blood clots, very high blood pressure, severe diarrhea, holes forming in the intestines, and kidney, liver, or heart failure.

Bevacizumab (Avastin)

Bevacizumab works by slowing the growth of new blood vessels. It can be used to treat advanced kidney cancer, either alone or along with another drug. It is most often used after other drug treatments have been tried.

It is given by infusion into a vein (IV), typically once every 2 weeks.

More common side effects of bevacizumab include:

• High blood pressure
• Feeling tired
• Headaches

Less common but possibly serious side effects include bleeding, blood clots, holes forming in the intestines, heart problems, and slow wound healing.

Axitinib (Inlyta)

Axitinib blocks several tyrosine kinases that help form new blood vessels in the tumor.

This drug can be used alone or with certain immunotherapy drugs, like pembrolizumab or avelumab, as a treatment for people with advanced kidney cancer.  Axitinib is a pill, typically taken twice a day.

Common side effects of axitinib include:

• High blood pressure
• Fatigue (feeling tired)
• Nausea and vomiting
• Diarrhea
• Poor appetite 
• Weight loss
• Voice changes
• Hand-foot syndrome
• Constipation
• Changes in liver and thyroid function (which can be seen on lab tests)

A small number of people develop blood pressure high enough to be life-threatening. This drug can also cause problems with bleeding, clotting, and wound healing.

Tivozanib (Fotivda)

Tivozanib blocks several tyrosine kinases involved in cancer cell growth and the formation of new blood vessels in the tumor.

This drug can be used in people with advanced kidney cancer.

Tivozanib is a pill, typically taken daily for 3 weeks followed by 1 week off. This cycle is then repeated for as long as the drug is still helpful.

Common side effects of tivozanib include:

• High blood pressure
• Diarrhea
• Nausea
• Poor appetite
• Cough
• Mouth sores
• Feeling tired
• Voice changes

Less common but more serious side effects can include heart problems, life threatening high blood pressure, blood clots, bleeding, poor wound healing, abnormal thyroid tests, and damage to the kidney.

Belzutifan (Welireg)

Belzutifan is a HIF inhibitor. It blocks a protein called hypoxia-inducible factor 2 alpha (HIF-2a), which is involved in both cancer cell growth and new blood vessel formation in tumors.

Belzutifan can be used:

In people with von Hippel-Lindau (VHL) disease who have kidney cancer and don’t need surgery right away.

• In people with advanced kidney cancer that has already been treated with a different targeted drug and with an immune checkpoint inhibitor (a type of immunotherapy drug).

This drug is taken as pills, typically once a day.

Common side effects of belzutifan include:

• Low red blood cell counts (anemia)
• Feeling tired and/or dizzy
• Nausea
• Headache
• Increased blood sugar levels
• Changes in lab tests showing the drug might be affecting the kidneys

Less common but more serious side effects can include very low red blood cell counts (severe anemia, which might require blood transfusions), and low oxygen levels in the body, for which you might need oxygen therapy or even be admitted to the hospital.

Drugs that target the mTOR protein

Temsirolimus (Torisel)

Temsirolimus works by blocking a protein known as mTOR, which normally helps cells grow and divide.

This drug can be used to treat advanced kidney cancers. It is usually used after other drug treatments have been tried. Temsirolimus is given by intravenous (IV) infusion, typically once a week.

The most common side effects of temsirolimus include:

• Skin rash
• Weakness
• Mouth sores
• Nausea
• Loss of appetite
• Fluid buildup in the face or legs
• Increases in blood sugar and cholesterol levels

Rarely, it can cause more serious side effects.

Everolimus (Afinitor)

Everolimus also blocks the mTOR protein.

This drug can be used to treat advanced kidney cancers. It can be used by itself or along with the targeted drug lenvatinib (see above), typically after at least one other drug treatment has been tried. 

Everolimus is taken as a pill, typically once a day.

Common side effects of everolimus include

• Mouth sores
• An increased risk of infections
• Nausea
• Loss of appetite
• Diarrhea
• Skin rash
• Feeling tired or weak
• Fluid buildup (usually in the legs)
• Increases in blood sugar and cholesterol levels

A less common but serious side effect is lung damage, which can cause shortness of breath or other problems.