Kidney cancer research

All treatments have to be fully researched before they can be adopted as standard treatment for everyone. This is so that

• We can be sure they work
• We can be sure they work better than the treatments that are available at the moment
• They are known to be safe

First of all, treatments are developed and tested in laboratories. For ethical and safety reasons, experimental treatments must be tested in the laboratory before they can be tried in patients. If a treatment described here is said to be at the laboratory stage of research, it is not ready for patients and is not available either within or outside the NHS.

Tests in patients are called clinical trials.  The trials and research section has information about what trials are including information about the 4 phases of clinical trials.  If you are interested in taking part in a clinical trial, visit our searchable database of clinical trials recruiting in the UK. If there is a trial you are interested in, print it off and take it to your own specialist. If the trial is suitable for you, your doctor will need to make the referral to the research team.

All the new approaches covered here are the subject of ongoing research. Until studies are completed and new treatments are found to work better than existing treatments, they cannot be used as standard therapy for cancer of the kidney.

Researchers are always trying to find out more about what causes certain types of cancer. A large study in Scotland is collecting blood and tissue samples from people with kidney cancer. These samples will be studied, along with information about how well people respond to treatment, to find out what they can tell us about the causes of kidney cancer.

Quite a lot of work has been done on genes that might increase kidney cancer risk. Researchers are looking into ways to try to predict who carries genes that increase kidney cancer risk. If they can do this, doctors could screen those people and treat them early if kidney cancer did develop.

Cancer Research UK scientists are looking at the von Hippell Lindau gene (vHL) to try to find out more about the process that leads to kidney cancer developing. Particular faults in the gene lead to very specific things happening in kidney cells. The scientists are looking for these gene faults and finding out what they do. We hope that this work will lead to new treatments that block kidney cancer growth. Recent research found that that mutations in a gene called PBRM1 are present in up to a quarter of patients with renal cell carcinomas, the type that accounts for 90% of kidney cancers. This finding might help researchers to develop tests and treatment in the future.

There is a trial to see if sorafenib can slow down the growth, or reduce the size, of kidney cysts or kidney cancer in people with von Hippell Lindau syndrome. Sorafenib is a type of biological therapy. While this trial is recruiting patients, you can find more information on our clinical trials database.

Researchers are also looking into trying to replace damaged genes. This is one of the newer approaches to cancer treatment. It is in the very early stages of clinical trials. There is a gene called the p53 gene, which is abnormal in many different types of cancer, including kidney cancer. The normal p53 gene tells a cell to self destruct if it is old or damaged. Cancer cells don't do this because they have an abnormal p53 gene.

If a normal p53 gene could be put back into kidney cancer cells, it may be able to stop the growth of the cancer, by signalling to the cancer cells to die off naturally as normal cells would. Scientists are also studying ways of trying to replace the von Hippell Lindau gene (vHL) with a normal one. This is very early research and we don't know if it will work yet. The main problem is how to get the replacement genes into the cancer cells.

Cancer Research UK is also supporting a trial which is looking into genetic causes of kidney cancer. This trial is looking at people who may have an inherited genetic fault or a medical condition that increases their risk of getting kidney cancer. There is more information about it on our clinical trials database. You can use this link and select 'kidney' from the drop down menu.

Surgeons and researchers continue to try to improve the results of cancer surgery and improve quality of life after surgery. Research is looking at

• Removing part of the kidney
• Combining surgery with newer drug treatments

Removing part of the kidney

A large trial looked into removing part of the kidney (partial nephrectomy) instead of the whole kidney (total or radical nephrectomy) in kidney cancer patients. The trial was trying to find out exactly who this type of operation should be offered to and which patients should still have their cancerous kidney totally removed.

The advantage of removing part of the kidney is that you still have the rest of it to fall back on, should anything happen to your other kidney. We are still waiting for the full results of this trial. But specialist surgeons already treat many small tumours (less than 4cm across) with a partial nephrectomy if possible. It is also used to treat some people with larger tumours up to 7cm across. So if you have a small enough tumour, in the right place, you will probably be offered this type of treatment now. If you think you may be suitable for this, talk to your surgeon. You may need referral to a specialist team to have the operation.

Combining surgery with newer drug treatments

The CARMENA trial is looking at whether surgery helps people who are having the biological therapy sunitinib for clear cell kidney cancer that has spread to other parts of the body. Treatment for kidney cancer has improved during the last few years with the development of new biological therapy drugs such as sunitinib. 

If the cancer has spread outside your kidney, having an operation to remove your kidney (a nephrectomy) will not cure the disease. A nephrectomy is a big operation to have. In the past, having surgery to remove the kidney helped some people to live longer. But with the new types of biological therapy now available, doctors don’t know if people still benefit from having this type of surgery. This trial aims to find out if having surgery to remove the kidney as well as sunitinib is better at treating clear cell renal cancer than sunitinib on its own.

Cryotherapy (also called cryosurgery) is a way of killing cancer cells by freezing them. The advantage of using cryotherapy is that it may offer the chance of cure without the risks of having to remove a kidney. Patients who benefit from this type of treatment most are those with an early stage kidney cancer that is less than 4cm across and who can't have surgery for other health reasons.

In July 2011 NICE said that cryotherapy for kidney cancer could be provided on the NHS. But it should be kept for people who are not fit enough for major surgery, or who refuse to have a major operation. They must have all the risks and benefits of the treatment explained to them beforehand. NICE also say that doctors must collect information on this treatment and how well patients do. This information is to be collected by the British Association of Urological Surgeons.

There is more information about cryotherapy for kidney cancer in this section of CancerHelp UK.

This is commonly known as microwave thermotherapy. Clinical trials have been done using this new treatment for a number of different types of cancer, including kidney cancer. It involves heating the kidney using microwave energy to kill off the cancer. This is very experimental and we need results from more trials before this would be considered standard treatment for any type of cancer.

Doctors usually call this radiofrequency ablation or RFA. It is another type of heat treatment. Like cryotherapy and other types of heat treatment, it is a local treatment. This means it can destroy tumour in the specific area it is aimed at. But it won't treat cancer outside that area.

RFA means using radiowaves to heat up and destroy cancer tissue. So far, doctors use it most often for cancer that has come back or for secondary cancer spread in the liver. RFA is being tested in a number of different types of cancer, including kidney cancer. Some trials have reported that it works well, but treatments may need to be repeated. There have been some trials looking at it as a first treatment, instead of surgery to remove the cancer. But it is too early to say whether the long term control of the cancer is as good as with conventional surgery.

There are several ways of giving this type of treatment. The commonest way is to put needles through the skin into the cancer. The doctor uses scans or ultrasound to make sure the needles are in the right place. You have this treatment with local anaesthetic. The most common side effect after RFA is pain in the treated area. Usually people are well enough to go home after the treatment and can take painkillers home with them.

NICE (The National Institute of Health and Clinical Excellence) have issued guidance on radiofrequency ablation for kidney cancer. They say that although it appears safe enough to use, there is not enough evidence yet to know how well it helps control symptoms. So at the moment NICE say you should only have RFA if surgery is not possible.

There has been some research into doing RFA as a keyhole surgery operation, using a laparascope. The researchers think you should only need to do this if it is difficult to put the needles in through the skin (because the cancer is too close to other body organs, for example).

HIFU stands for high intensity focused ultrasound. This means strong beams of sounds are directed precisely at the cancer and are capable of killing cancer cells. Doctors think this may be an alternative to surgery, and that in the future patients may be able to have a primary kidney cancer treated without needing an operation. There has been a clinical trial in the UK looking at HIFU for kidney cancer that can't be removed by an operation. And another trial looking at HIFU before surgery. This means the doctors can look at the cancer after it has been removed to see what effect the HIFU has had. These trials are no longer recruiting, and we are waiting for the results.

Biological therapy is treatment with substances that the body naturally makes to fight infection and disease. It works by encouraging the body's natural defence system, the immune system, to attack cancer cells. There is detailed information about biological therapy in CancerHelp UK. And there is information about using biological therapies for kidney cancer in this section. You can find out more about biological therapy trials for kidney cancer on our clinical trials database. Go to the advanced search and choose 'kidney cancer' from the dropdown menu of cancer types and 'biological therapy' from the list of treatment types. If you want to see all the trials, tick the boxes for closed trials and trial results.

Biological therapies are usually used alongside the standard treatments of chemotherapy or radiotherapy. Cancers have different gene mutations, even if they are basically the same type. Because of the different gene mutations, one person may have a cancer that is blocked by a particular biological drug and others won’t. In future, we are likely to have ways of checking who will respond to a treatment and who won’t so that we can use it to the best advantage. A great deal of basic scientific research has to be done to develop this type of treatment. The types of biological therapies currently being researched for kidney cancer include

• Interferon and IL-2
• Monoclonal antibodies
• Growth factor blockers
• Blood vessel growth blockers
• MTOR blockers
• Vaccines

Interferon and IL-2

Interferon and IL2 are 2 treatments that have been developed from naturally occurring body chemicals and can now be made artificially in large quantities. IL-2 that has been made in the laboratory as a treatment is called aldesleukin. We already know these drugs can help people with kidney cancer. But doctors are still researching the most effective doses of these drugs and when best to use them. Trials have looked at using a combination of IL2, interferon and fluorouracil chemotherapy. 

There is detailed information about interferon and kidney cancer and about IL-2 and kidney cancer in this section of CancerHelp UK.

Monoclonal antibodies

Bevacizumab (Avastin) has been shown in trials to stop or slow the growth of advanced kidney cancer.

In recent years, cancer researchers have developed a number of biological treatments that are being tested in different types of cancer. Some of the new drugs are monoclonal antibodies that target particular proteins on the surface of the cancer cells. A new treatment called ABR-217620 was recently tested, to see if giving it with interferon helps to fight advanced kidney cancer. ABR-217620 is made up of 2 proteins. One of these recognises the cancer cells, and the other stimulates the body's immune system to attack them. People in the trial were either given interferon with ABR-217620, or just interferon. This trial has closed and we are waiting for the results.

Another trial is looking at a monoclonal antibody called cG250, to see if it helps to stop clear cell kidney cancer from coming back after surgery.

Growth factor blockers

Many of the new biological therapy drugs are growth factor blockers. They are designed to stop cancer cells growing. Some of these drugs are known as tyrosine kinase blockers (inhibitors) or TKIs for short. Tyrosine kinases are chemical messengers (an enzyme) that play a part in the growth of cancer cells. 

The SUCCINCT trial is looking at combining the TKI drug sunitinib (Sutent) with GC chemotherapy for transitional cell cancer of the lining of the bladder, the pelvis of the kidney, or the tube that links the two (the ureter). The trial is for people whose cancer is locally advanced or has spread to another part of their body. It aims to find out whether adding Sutent to GC chemotherapy works better than GC chemotherapy alone and to find out which side effects it causes. The SuMR trial is looking at sunitinib for people with advanced kidney cancer. The trial team want to find out if having sunitinib before surgery, as well as after, improves treatment outcomes for this group of people.

The PISCES trial is comparing sunitinib with a new tyrosine kinase inhibitor called pazopanib (Votrient) as a first treatment for kidney cancer that has spread. The PANTHER trial is looking at pazopanib before surgery for kidney cancer that has spread to another part of the body. The researchers want to find out if there is a benefit to starting pazopanib before surgery and whether it causes any problems if you have pazopanib before surgery.

One trial is looking at giving the TKI sorafenib (Nexavar) to people whose kidney cancer has not spread anywhere else, and has been removed surgically. The researchers want to find out if it stops or slows down the cancer coming back, and how long it should be taken for. There is also a trial to see if sorafenib will shrink, or slow down the growth of, kidney cysts or kidney cancer in people with the genetic condition known as von Hippel Lindau syndrome. There is also a trial comparing a new drug (TKI258) with sorafenib in people who have clear cell kidney cancer that has come back after treatment (recurred).

One study is looking at TKI258 to treat transitional cell kidney cancer that has spread into the surrounding tissue (is locally advanced), or to another part of the body. The aims of this study are to find out if TKI258 can help people with advanced transitional cell cancer and what side effects it may cause.

Blood vessel growth blockers

Other types of biological therapies have been researched for kidney cancer. These include drugs such as thalidomide that reduce the blood supply to tumours to stop them growing. Doctors call these types of drugs anti angiogenic treatments. The COSAK trial is a phase 2 trial looking at 2 new anti angiogenic drugs. The trial is testing cediranib (also known as AZD2171) and saracatanib (also known as AZD0530) for people with clear cell kidney cancer that has spread to other parts of the body. The trial aims to find out if a combination of cediranib and saracatanib works better than cediranib on its own for clear cell kidney cancer that has spread. It also wants to learn more about the side effects of these 2 drugs. 
 

MTOR blockers

Temsirolimus (Torisel) is a type of drug called an mTOR blocker (inhibitor). It stops a particular protein called mTOR from working properly. mTOR controls other proteins that trigger cancer cells to grow. In a trial temsirolimus helped people with renal cell cancer that had spread to live longer than if they were treated with interferon. Temsirolimus has now been approved for this use in Europe. The National Institute for Health and Clinical Excellence (NICE) does not recommend temsirolimus as the first treatment people have for advanced kidney cancer because they do not think it is cost effective.

One study is looking at using everolimus for advanced kidney cancer that has spread to another part of the body. Everolimus is another type of mTOR blocker and is also called Afinitor. Doctors sometimes use everolimus for advanced kidney cancer that has come back either during or after treatment. The researchers think that using everolimus before surgery may help people with advanced kidney cancer. The ASPEN trial is comparing everolimus with sunitinib for renal cell kidney cancer that has spread. 

A current trial is comparing a combination of bevacizumab (Avastin) and everolimus with a combination of bevacizumab and interferon. The trial aims to see which of these 2 drug combinations is best for people with metastatic clear cell kidney cancer. A trial called RAPTOR is looking at everolimus for kidney cancer that has spread to other parts of the body. This trial is for people who have a particular type of renal cell cancer called papillary renal cell cancer. The aim of this trial is to find out if everolimus can help people with advanced papillary kidney cancer. There is another trial comparing everolimus and sunitinib for the most common type of kidney cancer (renal cell cancer) that has spread to other parts of the body.

Some renal cell cancers have large amounts of the growth factor receptors called EGFR and HER2. If the receptors are blocked, this can stop the cells from growing and dividing. A TKI drug called lapatinib (Tyverb) targets the receptors and has been tested in trials for advanced renal cell cancer. This research is still ongoing.

Vaccines

Vaccines are a type of immunotherapy. Cancer vaccines are designed to try to stimulate the body's own immune system to fight the kidney cancer. The immune system will naturally attack 'foreign' cells that are invading the body, such as bacteria and viruses. One problem with kidney cancer and other types of cancers is that the patient’s own immune system does not think that the cancer is foreign, so it does not try to get rid of it. Because cancer develops originally from normal body cells, cancer cells are harder for the immune system to spot.

There is research into vaccines to try to slow down or stop advanced kidney cancer. And there is also research into vaccines after surgery to try to lower the risk of the cancer coming back. It is still early days in kidney cancer vaccine research. Vaccines are available only in clinical trials, because this type of treatment is still highly experimental.

There are different ways to make vaccines. Some can be given to any kidney cancer patient, while others are made individually for each individual patient. You usually have cancer vaccines as a series of injections, normally just under the skin.

The types of vaccines being tested for kidney cancer are

• Tumour cell vaccines
• Dendritic cell vaccines
• Virus based vaccines

Tumour cell vaccines are made from an individual patient’s kidney cancer cells. The cells come from the tumour when it is removed during surgery. The researchers treat the cells in the lab so that they can no longer grow. And so that they are easier for your immune system to recognise. There are various ways of doing this. One is to attach something 'foreign' to the treated cancer cells to help your immune system learn to recognise them. For example, a bit of a known bacteria, such as TB. (If researchers use bacteria , they always make sure they only use an inactive part of the bacteria or treat them to make them harmless.)

A German trial that has now finished looked at a tumour cell vaccine after surgery to lower the risk of cancer coming back. They made the vaccine individually for each patient . All the patients had cancer confined to the kidney, with no spread of the cancer anywhere else. The researchers found some evidence that the vaccine might lower the risk of the cancer coming back. But this is still early days and it was not a large enough trial to be sure. One problem was that they weren’t able to make a vaccine for every patient. The attempt failed in one in six. We also need to find out more about which groups of patients the vaccine might help. Those with very early cancers may be less likely to need this type of treatment after surgery.

Dendritic cell vaccines are made from a type of white blood cell. Dendritic cells encourage the immune system to attack infected or cancerous cells. To make the vaccine, dendritic cells are removed from the blood and mixed with kidney cancer cells in a laboratory. Then you have the cells back to try to stimulate your immune system to pick up the cancer. Mixing the cancer cells with the blood cells is called priming the dendritic cells. This is proving quite difficult to do and most of this research is still at an early stage.

One trial looked at a cancer vaccine called IMA901 and GM-CSF for advanced clear cell renal cell cancer, to see if it could stimulate the immune system to stop the cancer growing, or even shrink it. The researchers found that IMA901 could help some people with advanced kidney cancer if it was given with cyclophosphamide. They say that more trials are needed to find out more about how much it may help.

Virus based vaccines are vaccines made from changed virus cells. The TRIST trial looked at how effective the TroVax vaccine is with 3 different treatments for advanced kidney cancer – interferon, IL-2, and sunitinib. It found that TroVax did not add much benefit for most people. But some of the people who had TroVax and IL-2 lived for longer than those who had the dummy drug and IL-2. The researchers say that further trials should be done to find out why.

There is quite a bit of research going on into chemotherapy for kidney cancer, although it is not used as often as it is for some other cancers. This is because better treatment results have been gained with other types of treatment such as biological therapies. But new drugs are being developed all the time. And there are always clinical trials looking into these.

Different types of kidney cancer respond to different treatments. Chemotherapy is used more often for transitional cell cancer (TCC) than it is for renal cell cancer. Transitional cell cancer is a type of cancer that can develop anywhere in the urinary system – that is, in the bladder, kidney or tubes connecting them (the ureters). The ODMIT C trial looked at giving mitomycin C straight into the bladder after surgery for transitional cell kidney cancer. The aim of this treatment is to try to stop the cancer coming back in the bladder after the affected kidney has been removed. The research team found that giving mitomycin C into the bladder helped to stop the cancer coming back for some patients. It didn't cause any serious side effects. The research team advised that doctors should consider giving mitomycin C to all patients who have surgery for TCC of the kidney.

There is also a trial using a drug called vinflunine for advanced transitional cell cancer of the kidney. This trial finished recruiting patients, so we are now waiting for the results.

Another trial for transitional cell cancer is looking at combining gemcitabine and oxaliplatin that has spread. This trial includes people whose cancer has continued to grow while having cisplatin.

One trial is looking at a combination of the chemotherapy drugs irinotecan, cisplatin and mitomycin C (IPM) for advanced kidney cancer. Another trial has been comparing the chemotherapy drugs gemcitabine and carboplatin with the combination of methotrexate, vinblastine and carboplatin for people with advanced kidney cancer. This trial is no longer recruiting patients and we are waiting for the results. Other drugs that have been tested in transitional cell cancer include docetaxel (Taxotere), cisplatin and tretinoin.

The GO-80 study is looking at combining gemcitabine with oxaliplatin, instead of cisplatin for transitional cell cancer that has spread. Oxaliplatin is similar to cisplatin but is less likely to damage the kidneys. So doctors hope that it will work as well at controlling the cancer but may cause less side effects.

In renal cell cancer, there are also trials looking into combining chemotherapy and biological therapies. To find these and other kidney cancer trials, go to our clinical trials database. Select 'kidney' from the dropdown menu.

Stem cell transplants are often used to treat other types of cancers especially leukaemia and lymphoma. Results from several small trials have shown that this treatment could help people with advanced kidney cancer that is no longer responding to any other treatment. This treatment carries many side effects and you would only be offered it as part of a clinical trial.

There is general information on stem cell transplants in the about cancer treatment section of CancerHelp UK.