Your drug treatments for kidney cancer will be based on the stage and grade of your cancer and your general health.
Staging is used to describe how big a cancer is and how far it has already spread, and doctors grade cancers to indicate how quickly or slowly a cancer is likely to grow and spread:
- Stage 1 – the cancer is confined to the kidney and is less than 7cm in size
- Stage 2 – the cancer is bigger than 7cm but still confined to the kidney
- Stage 3 – the cancer has started to spread outside the kidney to the adrenal gland or a major vein nearby. The cancer may have spread to no more than one nearby lymph node.
- Stage 4 – the cancer has spread to nearby tissues or organs and more than one nearby lymph node contains cancer cells OR the cancer has spread to other parts of the body further away.
Cancers are graded as low-, intermediate- or high-grade cancers to indicate how quickly the cancer is likely to grow and spread. Low-grade cancers grow slowly, while high-grade cancers are more aggressive and grow quickly.
Your doctors will tell you which treatment they think would be best for you. Sometimes they may offer you a choice of treatments. In any case, you should be sure you have been given enough information, and understood it, before you give permission for the treatment to start. Don’t be embarrassed about asking people to explain things again. And remember to ask about any aspects that are worrying you.
Biological therapies are drugs which are used to kill cancer cells or stop them from growing. Biological therapies are used to try to shrink or control advanced kidney cancer and help people to live longer. You may be given biological therapies for kidney cancer that has already spread, or is at high-risk of coming back after surgery.
Some people with advanced kidney cancer respond very well to biological therapies, and the treatment can control their cancer for a number of months or even years. There is a great deal of research going on to try to find out why certain patients do so well and which is the best combination of drugs to give to patients with advanced kidney cancer. You can get more information about clinical trials from the Kidney Cancer UK and Cancer Research UK (see the Clinical Trials fact sheet for further information).
Several different types of biological therapy are used for the treatment of advanced kidney cancer, including immunotherapy, targeted therapies, and monoclonal antibodies.
This approach stimulates the body’s own immune system to attack the cancer cells. It uses man-made copies of substances found naturally in the body. These include interferon-alpha-2a and interleukin-2. These immunotherapies are not often used for the treatment of kidney cancer anymore, as other drugs are more effective. New immunotherapies, such as PD-1 inhibitors (nivolumab), are now being tested for the treatment of advanced kidney cancer.
Interferon alpha-2a (Roferon-A® or IntronA®) works by helping to stop the cancer cells from growing, and by boosting the immune system to attack the cancer. Interferon is usually given three-times-a-week by an injection under the skin using a very fine needle. You, or a relative, can be taught to do this at home using a pen-injection device or a pre-filled syringe.
You can arrange for a nurse to visit you at home to help you manage the first few times, and give advice on managing any side-effects. These can be similar to ‘flu symptoms; chills, fever, headaches, and aches and pains in your back, joints and muscles. Taking paracetamol half an hour before an injection and then every six hours until the symptoms subside often helps. Other side-effects include; nausea, sickness, diarrhoea, loss of appetite, low blood pressure (that can make you feel dizzy or faint), feeling sad or depressed, and tiredness. The side effects tend to lessen as the treatment continues.
Interleukin-2 or aldesleukin (Proleukin®) stimulates a type of white blood cell, called a T-lymphocyte, to attack the cancer. T-lymphocytes are part of the immune system. It is usually given through a drip into a vein in the arm. Treatment is given in a series of cycles of five days followed by a break in treatment for a few days or weeks. The side-effects are similar to those of interferon, but are likely to be worse and vary depending on the dose.
The most common side effects include; chills, fever, headache, aches and pains, nausea and vomiting, and loss of appetite. Interleukin-2 may also cause changes to the pattern of your heartbeat, fluid on the heart or lungs, or problems such as low blood pressure and swollen hands and feet. This is why it is usually only given to patients in specialist cancer centres where doctors and nurses can help them manage the side-effects.
Immunotherapy, such as interferon-alpha and interleukin-2, used to be the main treatments for advanced kidney cancer. However, their use has been superseded by targeted therapies, which are more effective at controlling the cancer and have less severe side-effects. As a result, the use of immunotherapy for advanced kidney cancer has declined in recent years. However, a small minority of patients (about 5 per cent), who are otherwise healthy and well enough to withstand the severe side-effects, have a long-term durable response to high doses of interleukin-2. Interleukin-2 therefore still has a place in the treatment of a small percentage of patients where it offers the hope of durable remission.
Nivolumab (Opdivo®) is an anti-PD-1 (programmed death-1) monoclonal antibody which acts by blocking the receptor PD-1 on T-cells (part of the immune system), which reinvigorates the T-cells and allows them to attack the cancer cells. T-cells are often inactivated by a substance that cancer cells produce, which activates the PD-1 receptor on T-cells. Activating the PD-1 receptor causes the T-cell to become inactive so it doesn’t do its job and attack cancer cells. Nivolumab acts as an immunomodulator and stops the PD-1 receptor from being activated which in turn boosts the body’s own ability to attack cancer cells.
The PD-1 blockade is thought to specifically reinvigorate immune cells that are able to target cancer. It does not generally activate the entire immune system and this could help to reduce the side effects of the drug. Nivolumab is generally well tolerated but can cause inflammatory conditions in varying organs of the body.
Nivolumab is currently approved in America for use for metastatic kidney cancer. A clinical trial – CheckMate -025, a Phase III study was stopped early when nivolumab proved more significantly more effective in extending survival in advanced kidney cancer patients than everolimus. Nivolumab has just been recommended by NICE for use in metastatic melanoma and hopefully will be approved for advanced kidney cancer in the autumn.
One of the most promising advances in the treatment of kidney cancer has been the development of targeted therapies, such as tyrosine kinase inhibitors (TKIs) and mammalian target of rapamycin (mTOR) inhibitors. These drugs are now standard treatment for advanced kidney cancer.
Tyrosine kinase inhibitors (TKIs), such as cabozantinib (Cabometyx®) sunitinib (Sutent®), sorafenib (Nexavar®), pazopanib (Votrient®), and axitinib (Inlyta®) block the effects of a protein called tyrosine kinase, which is involved in new blood vessel growth that is essential for cancer cells to divide and grow. These treatments starve the tumour by stopping the development of a new blood supply (angiogenesis). Doctors call treatments that interfere with the development of a blood supply anti-angiogenic agents. Tyrosine kinase inhibitors also interfere with the growth of cancer cells by blocking the signals within the cancer cells that tell them to grow and divide, causing the cancer cells to die.
Tyrosine kinase inhibitors come as tablets or capsules that you swallow. Cabozantinib is capsules or tablets taken once a day at the same time each day with a glass of water, one hour before you eat or two hours after you eat. Sunitinib comes as a capsule, which is taken once-a-day for four weeks followed by a two-week break. Pazopanib, sorafenib and axitinib are tablets that are usually taken once or twice-a-day for as long as the treatment is helping.
The most common side-effects include: tiredness, stomach upsets from diarrhoea to nausea and vomiting, skin and hair discolouration/changes, red and blistered hands and feet, sore mouth, an increase in blood pressure, thyroid problems, blood problems, and loss of taste and appetite. Many of these side-effects can be controlled with medication and they do not affect everyone. You may only have one or two side-effects. A side effect may get worse through your course of treatment, or more side-effects may develop as the course goes on.
Potential side-effects to targeted therapies:
- Nausea and vomiting
- Skin and hair discolouration/changes
- Red and blistered hands and feet (palmar-plantar erythrodysaesthesia, PPE)
- Sore mouth
- Raised blood pressure
- Thyroid problems
- Blood problems (sunitinib)
- Loss of taste and appetite
Your clinical nurse specialist (specialist nurse) or doctor should give you a contact number for you to ring if you are worried about side-effects or have any questions. You need to tell your specialist nurse or doctor about your side-effects so they can help you manage them. You also need to tell your doctor about any other medicines you are taking, including vitamins, herbal supplements and other over-the-counter remedies.
In the UK, sunitinib and pazopanib are used as first-line treatment for advanced kidney cancer. Axitinib, pazopanib or sorafenib are recommended for use after first-line treatment with interferon or interleukin has failed to help, or if patients cannot tolerate these first-line treatments i.e. as a second-line treatment. Axitinib is also recommended for use as second-line treatment after sunitinib has stopped working, or if the patient cannot tolerate this treatment.
Although sunitinib, pazopanib, axitinib and sorafenib have all been licensed for the treatment of people with advanced kidney cancer, the National Institute for Health and Care Excellence (NICE) has issued guidance that recommends only sunitinib and pazopanib as first-line treatment options in NHS hospitals, and axitinib as second-line treatment after failure of a tyrosine kinase inhibitor or immunotherapy. In addition to sunitinib and pazopanib as first-line treatment, the Scottish Medicines Consortium (SMC), the equivalent to NICE for NHS Scotland, has approved the use of both axitinib and everolimus (see below) as second-line treatment for advanced kidney cancer after the failure of immunotherapy or sunitinib.
Another group of protein kinase inhibitors, called mTOR inhibitors, such as temsirolimus (Torisel®) and everolimus (Afinitor®), act in a similar manner to TKIs by interfering with the signalling pathway that controls tumour cell growth and angiogenesis. Temsirolimus is given through a drip in a vein in the arm over 30-60 minutes once-a-week for as long as it is working. Everolimus is a tablet that is taken once daily. MTOR inhibitors are treatments for advanced kidney cancer that has come back during or after treatment. Side-effects to mTOR inhibitors are similar to those for TKIs.
In the UK, temsirolimus can be used to treat patients with a poor outlook (prognosis) and everolimus is used as second-line treatment after sunitinib or pazopanib has stopped working or isn’t tolerated. Both temsirolimus and everolimus are licensed for the treatment of advanced kidney cancer in the UK; however, they have not been recommended by NICE and are therefore not available in NHS hospitals because they are considered to be too expensive. However, you may have treatment with mTOR inhibitors as part of a clinical trial or through a government funding scheme, such as the Cancer Drugs Fund.
You can find more information about targeted therapies on the Cancer Research UK website here.
Bevacizumab (Avastin®) is a monoclonal antibody, which recognises and blocks a protein in the blood called vascular endothelial growth factor (VEGF). VEGF acts on cells and is part of the signalling pathway that helps cancers to grow blood vessels. All cancers need a blood supply to be able to survive and grow. Like protein kinase inhibitors, bevacizumab starves the tumour by stopping the development of a blood supply and is therefore another anti-angiogenic agent. Bevacizumab is given in conjunction with interferon-alpha to boost the effect of interferon-alpha.
Bevacizumab is administered through a drip into a vein every two weeks. The first dose is given over an hour and a half and if you don’t have any problems, the infusion time can gradually be reduced to 30 minutes.
The most common side-effects associated with bevacizumab are high blood pressure during treatment, feeling sick, constipation, diarrhoea, fatigue, pain and weakness affecting your joints, muscles, chest and abdomen, numbness or tingling in fingers and toes, slow wound healing, protein in your urine and increased risk of bleeding. Most of these side-effects can be treated and they do not affect everyone. You need to tell your specialist nurse or doctor about your side-effects and any other medicines you are taking.
Drug treatments available on the NHS:
- Interferon alpha-2a (Roferon-A® or IntronA®)
- Interleukin-2 or Aldesleukin (Proleukin®)
- Sunitinib (Sutent®)
- Pazopanib (Votrient®)
- Axitinib (Inlyta®)
Drug treatments licensed for use but not available on the NHS:
- Sorafenib (Nexavar®)
- Bevacizumab (Avastin®)
- Everolimus (Afinitor®)
- Temsirolimus (Torisel®)