Oesophageal cancer research

• A quick guide to what's on this page
• Why research is important
• Research into preventing oesophageal cancer
• Research into Barrett’s oesophagus
• Surgery
• Endoscopic mucosal resection (EMR)

• Light therapy (PDT)
• Chemotherapy
• Chemotherapy and radiotherapy together
• Biological therapies
• REOLYSIN injections in advanced cancer
• Treatment for weight loss in advanced cancer

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 on the NHS or privately.

Tests in patients are called clinical trials. There are 4 phases of clinical trials. This is fully explained in the understanding clinical trials section of CancerHelp UK. 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 there is evidence that a new treatment is better than the current standard treatment, these treatments cannot be used as standard therapy for cancer of the oesophagus.

There is information below on

• Using drugs to lower risk
• Diet
• HPV infection

Using drugs to lower risk

Research into preventing cancer is often called ‘chemoprevention’ This means using drugs or diet to try to reduce the chance of cancer developing. Various anti inflammatory drugs have been studied in relation to cancer development. In one large US study, there were fewer oesophageal cancers in people who took aspirin regularly. Aspirin can cause serious side effects in some people, especially if it is taken regularly, so researchers are continuing to look into using other drugs.

Diet

Another known risk factor for cancer of the oesophagus is diet. Some countries have a higher rate of oesophageal cancer. This may be because of the foods they eat. There is a lot of research going on into why and how certain foods may increase the risk of cancer of the oesophagus and other types of cancer. As oesophageal cancer is more common in China and Japan, a lot of research looks into smoked, fermented or pickled foods that are popular in these countries. Drinking very hot liquids has also been linked to oesophageal cancer in some studies.

HPV infection

Although there are other more established risk factors for oesophageal cancer, in 1982 scientists found another possible risk factor for this type of cancer. It is a virus called the human papilloma virus (HPV). HPV is known to be linked to cervical cancer. There are many different types of the HPV but type 16 and 18 have been linked to cancer of the oesophagus, particularly to squamous cell cancers, but the exact role of HPV in the development of oesphageal cancer is not yet clear.

Researchers have used a technique called ‘polymerase chain reaction’ (PCR) to pick up HPV infection in the DNA of body cells. In future, we may be able to use this type of test to find people more at risk of developing oesophageal cancer. Researchers are even trying to develop a vaccine based on HPV16 that could be used to treat oesophageal cancers that carry HPV16. More research is needed before we will know how strongly HPV is linked to oesophageal cancer.

Barrett's oesophagus is a condition where cells lining the oesophagus have become abnormal, but are not yet cancerous. People with Barrett’s have a slight risk of going on to develop an oesophageal cancer.

The main research areas involving Barrett’s are as follows

• Research into the causes of Barrett’s oesophagus
• Research into the treatment of Barrett’s oesophagus
• Research into screening Barrett's oesophagus for cell changes

Research into the causes of Barrett’s oesophagus

Researchers are looking at why some people with Barrett’s get cancer and others don’t. This may help them to prevent it in the future. Or it may help to lead to a better understanding of risk factors, so that we may be able to develop screening for people at the highest risk. There is a study looking at people aged between 50 and 70 years who suffer from heartburn or acid indigestion. The researchers are trying to develop a screening test that can pick up Barrett's oesophagus early.

Some studies have suggested that an inherited faulty gene can cause Barrett’s oesophagus to develop. A study is currently taking place of people who have Barrett’s oesophagus and their families. The researchers hope to learn more about what causes this condition and what the risk to family members might be. You can read more about this trial on our clinical trials database. Choose oesophagus from the drop down list of cancer types.

If doctors could stop Barrett’s developing further, they would lower the rates of oesophageal cancer. We’ve already discovered that Barrett’s can be low grade or high grade. In people with ‘low grade’ Barrett’s the cells are mildly abnormal. Other people may have more serious cell changes and are said to have ‘high grade’ Barrett’s. Doctors think that the risk of high grade Barrett’s developing into cancer is greater than for low grade.

Research into the treatment of Barrett's oesophagus

Research is looking at ways of treating Barrett's oesophagus which may help stop oesophageal cancer developing. There is research into

• Light therapy (PDT) for Barrett's oesophagus
• Esomeprazole and aspirin
• Curcumin
• Cryotherapy

Light therapy (PDT) for Barrett's oesophagus

There is information about research into PDT for Barrett's oesophagus in the main light therapy section on this page.

Esomeprazole and aspirin

Other researchers are looking into using esomeprazole, with or without aspirin, as a way of stopping Barrett’s oesophagus turning into cancer. Esomeprazole is a type of drug called a proton pump inhibitor (PPI). It reduces the amount of acid produced by the stomach. Doctors think that esomeprazole may help to prevent Barrett's oesophagus developing into cancer. But they are not sure yet how well it will work. We think that irritation from stomach acid causes the cell changes in the oesophageal lining. So if the amount of stomach acid you produce is lowered, this may help to protect the cells near where the oesophagus joins the stomach. Aspirin is included in this trial because there is some evidence that it may help prevent cancer. There have been 2 separate trials for men and women looking into this. They are no longer recruiting patients, and we are waiting for the results.

Curcumin

A trial in Wales is looking at the spice curcumin to see if it can help treat Barrett’s oesophagus. This is a small pilot study and you can’t volunteer to take part. But you can read more about it on our clinical trials database.

Cryotherapy

Researchers in the USA have had promising results using cryotherapy to treat Barrett's oesophagus once the oesophageal cells have started to change. They put a small tube into the throat, and use liquid nitrogen to freeze these cells before they can become cancerous. The damaged cells will fall off, allowing normal cells to replace them. This treatment is being used in some hospitals in the USA, but more research is needed.

Research into screening Barrett's oesophagus for cell changes

People with Barrett's oesophagus usually have regular check ups called endoscopies. The doctor takes about 10 to 20 samples of tissue (biopsies) from your oesophagus. These are sent off to the lab and checked to see if the cells are getting more abnormal. This usually takes about 3 weeks. There is a study looking at a new technique called an 'optical biopsy', which may be able to tell straight away if the cells in your oesophagus have become more abnormal, or if there are any cancer cells present. If the optical biopsy is as good as endoscopy at picking up cell changes, it could mean that people with Barrett's oesophagus will need to have less biopsies in future. A trial called the BOSS study is looking at whether it is better to monitor people with Barrett's oesophagus every 2 years or to wait until they have a change in their symptoms. There is more information about these studies on our clinical trials database.

There is research into new ways of doing surgery for oesophageal cancer. These include

• Keyhole surgery
• Taking out lymph nodes during surgery

Keyhole surgery

It is now possible to remove all or part of your oesophagus without making a large opening in your chest. This technique is often referred to as 'keyhole surgery'. The medical name for this particular operation is a 'thoracoscopically assisted oesophagectomy', or a 'minimally invasive oesophagectomy', so you may hear your doctor use one of these phrases. In August 2006 NICE (National Institute for Health and Clinical Excellence) decided that this operation was safe and effective enough to be available in the NHS, as long as the surgeon has specialist experience and training in this procedure.

This operation is done under general anaesthetic and is carried out in 2 stages. Firstly the surgeon will collapse one of your lungs. It will be inflated again after the procedure. The surgeon then makes 4 - 6 small cuts in your chest on the same side as the collapsed lung. A camera connected to a screen and video recorder is inserted through one of these holes and the surgeon puts the instruments needed for the operation through the other holes.

The second stage of the operation is when the surgeon attaches the remaining section of your oesophagus to your stomach. This can be done by traditional open surgery, where the surgeon makes a large cut in the abdomen. Or by a similar 'keyhole' technique (laparoscopically). This means that, as in the first stage of the operation, a camera (a laparoscope) is put through a cut, this time in the abdomen, allowing the surgeon to complete the operation through the small cut.

Keyhole surgery takes longer than a traditional, open oesophagectomy, and the surgeon may not always be able to remove all the cancer using this technique. In a small number of cases it has been necessary to switch to an open technique during the operation. But it is hoped that this type of surgery may lead to less pain and fewer complications after the operation, although doctors are not sure of this yet.

Taking out lymph nodes during surgery

When you have surgery to remove an oesophageal cancer, your surgeon will take out all the lymph nodes nearest to the tumour and your gullet. This is because they may contain cancer cells, which could continue to grow. So removing them can lower the risk of the cancer coming back in the future. If there is a reason to suspect that lymph nodes further away also contain cancer cells, your surgeon will remove these nodes too.

There is a lot of debate around the world about whether routinely taking out more lymph nodes would lower the risk of the cancer coming back even more. Trials have been done to try to show whether or not taking out lymph nodes further away from the cancer can lower recurrence rates.

We don’t have the research evidence yet to say that taking out more lymph nodes routinely will help people. Doctors have to weigh up the possible increased side effects against the likely benefit. There is no point in doing more complicated surgery if it isn’t going to help.

If your cancer is at a very early stage, and still only on the lining of the oesophagus (the mucosal layer), it may be possible to remove it using this technique. The doctor puts a tube called an endoscope down your throat. The endoscope contains a camera so the doctor can see inside your body. The endoscope can be used to inject fluid into the layer of cells below the cancer, which makes the cancerous area stand out from the rest of the tissue. Then a thin wire (snare) is used to remove the cancer. The most common side effects are bleeding and a narrowing of the oesophagus, which can happen some time after the procedure. You might have photodynamic therapy after EMR, to try to kill any cancer cells that are left.

PDT uses light to kill cancer cells. You first take a drug that makes your body cells sensitive to light. Then the doctor shines a very bright light onto the cancer cells. This activates the drug and kills the cells. PDT is sometimes used for cancer of the oesophagus. Doctors may use it in advanced cancer, to shrink a blockage in the gullet. There is information about PDT for advanced oesophageal cancers in this section of CancerHelp UK.

PDT has been studied in people with stage 1 cancer of the oesophagus. Researchers hope it might be an alternative treatment for people not well enough to have surgery. NICE (The National Institute for Health and Clinical Excellence) have issued guidance on PDT for early oesophageal cancer. They say that this treatment is quite new, and there are still uncertainties about how well it works, particularly in the long term. NICE suggest that doctors can offer patients this treatment, but they should tell you all about the benefits and drawbacks first. Your doctor should make sure you understand that this is a new treatment that is still being tested.

NICE also recommend that doctors follow up patients who've had PDT to see how well they do. Doctors should enter patients into clinical trials if possible. This will all help in finding out how well PDT works in treating early oesophageal cancer, particularly in the longer term. Also, different drugs have been tested for use with PDT.

Researchers are currently looking into treating both low grade and high grade Barrett’s with PDT. They hope that this treatment will destroy the abnormal cells and so stop cancer from developing in the first place. A trial is currently testing different drugs for PDT. There is more information about this trial on our clinical trials database. Choose 'oesophagus' from the drop down menu of cancer types to find them.

NICE have issued guidance to doctors about using PDT to treat high grade Barrett's oesophagus. Overall, most of the patients in clinical studies looking into PDT have done well. The very abnormal cells went away. But NICE say these studies were too small to draw firm conclusions about the outcome of this treatment, particularly long term. In other words, we need to carry on testing it and following up patients for longer before we know how well it can prevent oesophageal cancer from developing.

Many clinical trials are underway, testing combinations of newer chemotherapy drugs. Doctors continue to study different combinations of chemotherapy drugs, different doses, or different ways of giving them. The aim of this type of research is to get better results when treating oesophageal cancer with chemotherapy. This is quite complicated because the research has to be carried out for different stages of cancer. Just because a combination of chemotherapy drugs helps with advanced cancer, this doesn’t necessarily mean that it will help to stop your cancer coming back if you have the same treatment before surgery.

One trial is comparing two combinations of chemotherapy before surgery for oesophageal cancer. These combinations are Cisplatin and 5FU (CF) and ECX. Doctors want to find out which is the best combination to use before surgery. While they are recruiting, these trials will be listed on our clinical trials database. Choose 'oesophageal' from the drop down list of cancer types.

Another trial is looking at giving oxaliplatin and 5FU before surgery instead of cisplatin and 5FU. Doctors want to find out if oxaliplatin works better than cisplatin in this situation. You can find more information about this on our clinical trials database.

In past trials, a combination called ECF has been very effective for advanced oesophageal and stomach cancers. This combination is made up of epirubicin, cisplatin and 5FU. But doctors are continuing to try to improve the effectiveness and find better ways of giving treatment. 5FU is now available as tablets, as a drug called capecitabine. So doctors are now testing ECX, which is epirubicin, cisplatin and capecitabine. Other combinations being looked at also have epirubicin and either 5FU or capecitabine, but with another drug called oxaliplatin instead of cisplatin.

A clinical trial called REAL 2 compared the chemotherapy drugs 5FU with capecitabine, and cisplatin with oxaliplatin in stomach and oesophageal cancer that has already spread. The results showed that capecitabine worked as well as 5FU, and oxaliplatin worked as well as cisplatin. And the quality of life of people on the different chemotherapy treatments was similar.

In a small trial, doctors are testing ECF chemotherapy with a drug called decitabine which may make the cancer cells more sensitive to treatment. This is an early phase trial for people with advanced oesophageal cancer.

Some research has been carried out with drugs called taxanes (docetaxel (Taxotere) and paclitaxel (Taxol)) in advanced oesophageal cancer. The results are promising but more research needs to be done to compare this treatment with the drugs that are currently considered standard treatment.

The COUGAR-02 trial is looking at how well docetaxel works for people with advanced oesophageal cancer who have already had one course of chemotherapy that has not shrunk the tumour, or the tumour has come back afterwards.

One research trial is looking at blood samples from people having ECF chemotherapy for oesophageal cancer. Differences in certain genes and proteins can affect the way that cancers grow and spread. The differences can also affect how well chemotherapy works. So a trial is looking at many proteins and the DNA in the liquid part of the blood (serum). The researchers hope this will help to understand more about how treatments work.

You can find information about these trials on our clinical trials database. Choose 'oesophagus' from the drop down list of cancer types.

Evidence suggests that people who have chemotherapy and radiotherapy together (chemoradiotherapy) before surgery may do better. A paper looking at all the different trial results together, showed that survival rates 2 years after treatment improved by 13 out of every 100 patients (13%) who had chemoradiation before surgery.

It is important to realise that not every person treated will benefit. Researchers sometimes work out how many people need to have a new treatment to make sure that one cancer death is prevented. For this treatment in oesophageal cancer, they worked out that 1 extra person will survive for every 8 treated. Llike all statistics, this is an average and no one can predict what will happen to any one person. This combined treatment may be particularly suitable for squamous cell cancers. While it helps adenocarcinomas, these also respond well to chemotherapy on its own before surgery. It's also important to remember that chemoradiotherapy is an intensive treatment and has significant side effects.

Research is still going on into this combined treatment for other situations in oesophageal cancer. When you are looking at this research, make sure you know what is being investigated. Combination therapy is still being investigated

• Before surgery in cancers too advanced to remove, to try to make surgery possible
• After surgery to try to lower the risk of cancer coming back
• Alongside biological therapy (cetuximab) to try to cure stage 1, 2 or 3 cancers. See the clinical trials database for more information

New treatments have to be tested in all the circumstances in which they may be used. We can't assume that a treatment will help stop cancers from coming back because it has been successful in shrinking an advanced cancer.

Biological therapies are treatments made from substances that occur naturally in the body. Or treatments that are developed from naturally occurring body substances. There are many different types of biological therapies, including

• Growth factor blockers
• Bortezomib (Velcade) for gastro-oesophageal junction cancer
• Vaccines
• Monoclonal antibodies

Growth factor blockers

Cells signal to each other by making and releasing proteins called growth factors. The growth factors encourage the cells to grow and multiply. The growth factors lock into other proteins, called receptors, on the cells' surface. Once the receptor has its growth factor locked in, it fires a signal into the cell, telling it to grow and divide into more new cells.

Cancer cells commonly make too much of many of these proteins. If we can block these proteins, we may be able to stop or slow down the growth of cancer cells. One type of growth factor blocker is called a tyrosine kinase inhibitor because it blocks a growth factor enzyme called tyrosine kinase. An example of a TK inhibitor is gefitinib (Iressa). It blocks one of the receptors, called epidermal growth factor receptor or EGFR. An early trial of gefitinib for advanced oesophageal cancer showed encouraging results. A phase 3 trial is now open for people whose oesophageal cancer has started to grow again after chemotherapy. You can read more about this trial on our clinical trials database. Choose oesophogeal cancer from the drop down menu.

Bortezomib (Velcade) for gastro-oesophageal junction cancer

Bortezomib is a type of biological therapy called a proteasome inhibitor. Proteasomes are substances found in all cells that help break down proteins. Bortezomib interferes with the way they work, causing a build up of proteins and making the cells die. Trials have shown that bortezomib also makes cancer cells more sensitive to some types of chemotherapy. A small early trial is looking into how well bortezomib works, with chemotherapy, in advanced cancer of the gastro-oesophageal junction, that cannot be removed surgically. Everyone on the trial has up to 8 cycles of EcarboX chemotherapy. This is epirubicin, carboplatin and capecitabine (Xeloda). They will also have different doses of bortezomib. This is so the researchers can find out the best dose to give, and learn more about the side effects of this treatment. There is more information about this trial on our clinical trials database.

Vaccines

This is very early research indeed in oesophageal cancer. Vaccines in cancer treatment are usually used to try to stop the cancer from coming back after it has been treated. The vaccines are designed to try to make your immune system recognise and attack cancer cells. Cancer cells are 'foreign' to the body, in that they are not normal cells. But they develop from normal cells originally, so it is difficult for your immune system to recognise them.

A vaccine is being tested at the moment based on a protein called CEA (carcino-embryonic antigen). The cells of many different cancer types make too much CEA. It is quite common in cancers of the digestive system, including oesophageal cancer. This vaccine is designed to make the immune system seek out cells with too much CEA and kill them. You can find out more about this trial on our clinical trials database. Pick oesophagus from the drop down list of cancer types.

Monoclonal antibodies

There is a lot of research going on into the use of monoclonal antibodies (MABs) to treat cancer. MABs are proteins, made in the laboratory from a single copy of a human antibody. Monoclonal just means 'all of one type'.

They act in the same way as immune system proteins that seek out and kill foreign matter in your body, such as bacteria and viruses. MABs are designed to recognise abnormal proteins on the outside of cancer cells.

The REAL3 trial is looking at a MAB called panitumumab (or Vectibix). This drug acts like a growth factor blocker. Doctors want to find out if EOX chemotherapy (epirubicin, oxaliplatin and capecitabine) works better against advanced oesophageal cancer if panitumumab is given with it. You may be able to join this trial if you have stage 3 or 4 oesophageal cancer which cannot be treated with surgery or combined chemotherapy and radiotherapy. You can find out more about this trial on our clinical trials database.

There has been a small trial in Manchester of an MAB called CP 675 206. This is being tested in patients whose oesophageal cancer has come back after treatment. The aim of the trial is to find out if CP 675 206 is effective against cancer cells in the oesophagus (foodpipe), but it is a very new treatment and doctors are not sure how well it will work. This trial has now closed and we are waiting for the results.

Doctors are looking into using a virus called reovirus to help fight advanced oesophageal cancer. It rarely causes any symptoms, but it can kill cancer cells. One trial is looking at whether the reovirus and radiotherapy will work better together than they would separately. The virus is injected straight into the tumour. This trial has closed and we are waiting for the results.

Another trial is looking at how well reovirus works with paclitaxel and carboplatin chemotherapy for tumours that continue to grow despite treatment. This trial has also closed and we are waiting for results. Both these trials will tell us more about the side effects of reovirus treatment.

Researchers are trying to find out if the drug thalidomide can help slow down or stop weight loss in people who have advanced cancer. You can find more information about this trial on our clinical trials database.