Targeted therapies for kidney cancer

As researchers have learned more about the molecular and genetic changes in cells that cause cancer, they have been able to develop newer drugs that specifically target some of these changes. These targeted drugs work differently from standard chemotherapy drugs and have different side effects. Targeted drugs are proving to be especially important in diseases such as kidney cancer, where chemotherapy has not been shown to be very effective.

The term targeted therapy may not be the most accurate way to describe these newer drugs, as even traditional chemotherapy targets certain cellular functions. However, this is the term commonly used for newer agents that have a more focused mechanism of action

Several targeted drugs have been approved by the US Food and Drug Administration for use against advanced kidney cancer. These include drugs that stop angiogenesis (growth of the new blood vessels that nourish cancers) and drugs that target other important cell growth factors. These drugs are often used as the first line of treatment against advanced kidney cancers. While they may shrink or slow the growth of the cancer, it doesn't seem that any of these drugs can actually cure kidney cancer.

Doctors are still learning the best ways to use these targeted drugs against advanced kidney cancers. As of now, they are most often used one at a time. If one doesn't work, another may be tried. It's not yet known if any one of these drugs is clearly better than the others, if combining them might be more helpful than giving them one at a time, or if one sequence is better than the other. Studies are being done to help answer these questions.

Sorafenib (Nexavar^®)

This drug has been shown to slow the progression of the cancer in some patients with advanced disease. It acts by blocking both angiogenesis and growth-stimulating molecules in the cancer cell. Sorafenib does this by blocking several important cellular enzymes called tyrosine kinases that are important for cell growth and survival. It is taken as a pill. The most common side effects seen with this drug include fatigue, rash, diarrhea, increases in blood pressure, and redness, pain, swelling, or blisters on the palms of the hands or soles of the feet (hand-foot syndrome).

Sunitinib (Sutent^®)

Sunitinib also blocks several tyrosine kinases, but not the same ones as sorafenib. This drug is a pill that has been shown to shrink or slow the progression of kidney cancer in many cases. It attacks both blood vessel growth and other targets that stimulate cancer cell growth. The most common side effects are nausea, diarrhea, changes in skin or hair color, mouth sores, weakness, and low white and red blood cell counts. Other possible effects include tiredness, high blood pressure, congestive heart failure, bleeding, hand-foot syndrome, and low thyroid hormone levels.

Temsirolimus (Torisel^®)

Temsirolimus is given as an intravenous (IV) infusion. It works by blocking a cell protein known as mTOR, which normally promotes cell growth and division. This drug has been shown to be helpful against advanced kidney cancers that have a poorer prognosis because of certain factors. The most common side effects of this drug include skin rash, weakness, mouth sores, nausea, loss of appetite, fluid buildup in the face or legs, and increases in blood sugar and cholesterol levels. Rarely, more serious side effects have been reported.

Everolimus (Afinitor^®)

This drug also blocks the mTOR protein. It is taken as a pill once a day. Everolimus is used to treat advanced kidney cancers after other drugs such as sorafenib or sunitinib have been tried. Common side effects of this drug 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), and 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.

Bevacizumab (Avastin^®)

This is an IV drug that works by slowing the growth of new blood vessels. Recent studies have shown it may be helpful against kidney cancer, especially when used with interferon-alpha. Bevacizumab is usually tolerated well by patients, but it can cause serious side effects such as increases in blood pressure, bleeding or blood clotting problems, and wound healing problems.

Pazopanib (Votrient^®)

Pazopanib is another drug that blocks several tyrosine kinases. These kinases are involved in cancer cell growth and the formation of new blood vessels. It is taken as a pill once a day. Common side effects include high blood pressure, nausea, diarrhea, headaches, low blood cell counts, and liver problems. In some patients this drug causes lab test results of liver function to become abnormal, but it also rarely leads to severe liver damage that can be life threatening. As with bevacizumab, problems with bleeding, clotting, and wound healing can occur, as well. It also rarely causes a problem with the heart rhythm or even a heart attack. If you are taking this drug, your doctor will monitor your heart with EKGs as well as check your blood tests to check for liver or other problems.

Axitinib (Inlyta^®)

This drug also inhibits several tyrosine kinases, including some that are involved in the formation of new blood vessels. It is taken as a pill twice a day. Common side effects include high blood pressure, fatigue, nausea and vomiting, diarrhea, poor appetite and weight loss, voice changes, hand-foot syndrome, and constipation. In studies, high blood pressure requiring treatment was fairly common, but in a few patients it got so high that it was life-threatening. As with bevacizumab, there may be problems with bleeding, clotting, and wound healing. In some patients, lab test results of liver function can become abnormal. Axitinib may also cause the thyroid gland to become underactive, so your doctor will watch your blood levels of thyroid hormone while you are on this drug.