Stomach 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 we already have
• 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 clinical trials database of trials recruiting in the UK. Pick 'stomach' from the drop down menu of cancer types. 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 refer you to the research team. The database also has information about closed trials and trial results.

Remember - all these new approaches are the subject of ongoing research. Until studies are completed that show these new treatments to be effective, they cannot be used as standard therapy for stomach cancer.

Researchers think that some people may have an inherited faulty gene that might increase their risk of developing stomach cancer. One study is looking at people who have 2 or more relatives with stomach cancer to see if they have genetic faults. They are also looking for any genetic faults in people who were diagnosed with stomach cancer before the age of 40.

The SOCS study is hoping to learn more about the known risk factors for stomach cancer and also look for new genetic or environmental risk factors. The researchers want to find out how our environment interacts with our genes and how this affects risk of developing stomach cancer.

Research into preventing cancer with drugs or other agents is called chemoprevention. Research is looking at using

• Antioxidants
• Antibiotics
• Diet

to help prevent stomach cancer.

Antioxidants

Eating a diet high in fresh fruit and vegetables seems to prevent stomach cancer. Some scientists believe that antioxidant vitamins and minerals may help prevent cancer when included in a healthy, balanced diet. These antioxidants, and other substances in fresh foods, may help to prevent damage to the stomach lining that can lead to cancer. We do not know for sure whether eating these can help prevent cancer, because this is a very difficult thing to prove. In theory, antioxidants help to prevent body cells being damaged by oxygen particles called free radicals. The damage can lead to the cells becoming cancerous.

Antibiotics

Clinical trials are looking at whether giving antibiotics to people who have a chronic infection of the bacteria Helicobacter pylori will help prevent stomach cancer. Helicobacter pylori (HP) is a known cause of stomach cancer. But most people who have this infection will not develop stomach cancer. So there must be other factors at work. Doctors need to know exactly what the risk is, or many people at low or no risk of stomach cancer would be treated with antibiotics that they didn't really need.

Some research has looked into screening for Helicobacter Pylori. People found to have the infection were treated and everyone in the trial is being followed up to see who develops stomach cancer in the future. It is easier to screen for HP than it is for stomach cancer - it just takes a breath test. But it will take many years before we know if HP screening is effective in helping prevent stomach cancer.

Diet

The incidence of stomach cancer varies from country to country around the world. This may be explained to some extent by differences in diet. A diet high in very salty foods increases the risk of stomach cancer. Stomach cancer levels are very high in Japan where very salty pickled foods are popular. But these foods are not typically eaten in the UK and stomach cancer rates here are lower than they are in Japan.

Smoked, barbecued, and preserved foods may also increase risk of stomach cancer. Preserved foods include cured meats, such as bacon and ham. A diet high in fresh fruit and vegetables may lower risk of stomach cancer.

We need much more detailed information about the link between diet and cancer. A major study has been going on in the UK and 9 other European countries, into the links between diet and cancer. This study is called The European Prospective Investigation of Cancer (EPIC). The trial started in 1993 and continues to produce reports on diet and a variety of cancers. There is more information about diet and cancer in the cancer and causes section.

Doctors can use chemotherapy, radiotherapy and surgery or a combination of these to treat stomach cancer. The treatment the doctor chooses depends on the size of the cancer and how far it has grown. But doctors cannot easily tell which treatment will work best for each person. They are always looking for ways to improve treatment. Doctors now have a way of looking at a very large number of genes in cancer cells. This is called gene expression profiling. Researchers are looking at genes in stomach cancers to see if this can help them work out who is most likely to benefit from certain treatments.

Research is being carried out into

• Surgery for small, early stomach cancers
• Keyhole surgery
• Making a new stomach

Surgery for small, early stomach cancers

For early stage stomach cancer the usual treatment is to remove part or all of the stomach. Some doctors in the UK are trying a technique developed in Japan for cancers smaller than 3cm. The surgeon uses an endoscopy tube that can greatly magnify the area. Acetic acid liquid is used to show up the area of the tumour more clearly. The surgeon removes just the cancer and a small surrounding area of healthy tissue. This type of surgery is called endoscopic mucosal resection (EMR) or endoscopic submucosal dissection. There is no wound on the outside of the body. In 2009 the Cochrane Library reviewed all the research so far into endoscopic mucosal resection. It is not clear whether EMR works as well as the standard surgery. The researchers recommend that trials are carried out. You can read the Cochrane Library review into endoscopic mucosal resection on their website.

Keyhole surgery

Surgery for stomach cancer is usually done through a cut into the abdomen (laparotomy). Laparoscopy is already used to help stage stomach cancers and there is increasing interest in using it to treat stomach cancer. Laparoscopy looks into the stomach using a tube passed through a small cut. There is less scarring after laparoscopic surgery and time spent in hospital is generally shorter. Some studies show that patients feel better more quickly afterwards. But it is not suitable for people with larger cancers or advanced disease.

A new type of laparoscopic surgery combines an endoscopy with a laparoscopy. This is called laparo endogastric surgery or laparoscopic resection. Because it is a new procedure we don’t yet know how good it is at removing cancer.

The National Institute for Health and Clinical Excellence (NICE) have issued guidance on laparo endogastric surgery. They say that there is not yet enough evidence on how safe or effective it is. And that doctors should make sure that patients are aware of these uncertainties. They also recommend that laparo endogastric surgery should only be carried out by doctors specialised in laparoscopic surgery.

Making a new stomach

Some clinical trials are looking into removing the stomach and then forming a small pouch from the small bowel in its place. A review looked at a number of these clinical trials and the results were published in 2009. They compared the results of people who had their stomach removed and a pouch formed with people who had their stomachs removed and did not have a pouch. The review found that forming the pouch does not extend the time it takes the doctor to do the operation or how long people have to stay in hospital afterwards. Patients who had a pouch had fewer problems with heartburn and had a better food intake after the operation. The review also found that people’s quality of life improved with a pouch compared with the people who did not have one. We still need longer term results to know for sure how helpful this operation is. This procedure is still being researched and is not widely available in the UK.

The MAGIC trial looked at treating people with stomach cancer that could be removed with chemotherapy before and after surgery. This is called peri operative chemotherapy. Results showed that chemotherapy helped to reduce the size of the cancer and made it easier to remove fully with surgery. Having chemotherapy before and after surgery also helped stop the cancer coming back and helped people live longer. As a result of this trial, peri operative chemotherapy became standard treatment.

Following on from this, researchers now want to see if it is helpful to add the biological therapy bevacizumab to chemotherapy before and after surgery.

Research has looked into using chemotherapy and radiotherapy together to see if it can help stop stomach cancer from coming back after surgery. Having both treatments can be difficult to cope with when recovering from a big operation. We need more research before we know whether this treatment really would help. Until then, it is not used routinely.

At the moment, chemotherapy is mainly used to try to shrink and control advanced stomach cancers. Doctors are always trying to get better response rates. So they test new drugs and new combinations of drugs.

Doctors are testing the standard ECF combination 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 stomach cancer.

The COUGAR-02 trial looked at how well docetaxel worked for stomach cancer that had come back after chemotherapy. The researchers found that on average people who had docetaxel lived longer than people who just had treatment to control symptoms.

The PEP0206 study is looking at irinotecan, docetaxel and a new chemotherapy called PEP02 for advanced cancer of the stomach that has continued to grow after previous chemotherapy.

If you are interested in reading about clinical trials for stomach cancer, please visit our searchable clinical trials database. Choose 'stomach' from the drop down list of cancer types.

Intraperitoneal chemotherapy is occasionally used when cancer cells have spread onto the inside of the abdominal wall and makes the abdomen swell with fluid (ascites). A small cut is made into the abdomen and a tube called a catheter is put through. The fluid in the abdomen is drained out and a chemotherapy infusion is put into the abdominal cavity.

Researchers in Europe and Asia are starting to look at hyperthermic intraperitoneal chemotherapy (HIPEC) after surgery for stomach cancer. The chemotherapy is heated to a certain temperature before being put into the abdominal cavity immediately after surgery.

One research trial is looking at blood samples from people having chemotherapy for stomach 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 the proteins and the DNA in the liquid part of the blood (serum). The researchers hope this will help them to understand more about how chemotherapy works. You can find details of this trial on our clinical trials database. Pick 'stomach' from the dropdown list of cancer types.

Biological therapies are treatments that are developed from natural body substances. There is research into

• Monoclonal antibodies
• Drugs to block cancer growth signals
• Bortezomib (Velcade)
• Everolimus
• Heat shock protein inhibitors

Monoclonal antibodies

A monoclonal antibody (MAB) is a protein made in the laboratory from a single copy of a human antibody. The REAL3 trial is looking at a MAB called panitumumab (Vectibix). This drug acts like a growth factor blocker. Doctors want to find out if standard EOX chemotherapy (epirubicin, oxaliplatin and capecitabine) works better against advanced stomach cancer if panitumumab is given with it. 

Monoclonal antibodies can target growth factors that encourage blood vessels to grow. Drugs that stop new blood vessels growing are called antiangiogenics. (Angiogenesis means growth of blood vessels.) Cancers need to grow their own blood vessels so that they can be sure of getting enough food and oxygen. If there aren't blood vessels carrying these nutrients into the centre of the tumour, it will die. VEGF is a protein which promotes blood vessel growth. The drug bevacizumab (Avastin) works by blocking VEGF. The ST03 trial is looking at whether it is better to give bevacizumab alongside chemotherapy before and after surgery or just chemotherapy on its own.  

Drugs to block cancer growth signals

There are receptors on the surface of body cells that are triggered by growth chemicals. Cancer cells usually have too many receptors, which is one reason why they grow too fast and in an uncontrolled way. Drugs that block these receptors are called inhibitors.

Two of the groups of chemicals that encourage cell growth are called protein kinases and tyrosine kinases. Imatinib and lapatinib (Tyverb) are tyrosine kinase inhibitors being tested for advanced stomach cancer.

The LEO trial is a phase 2 trial looking at lapatinib (Tyverb). It is for people whose cancer cells have a protein called HER2. Lapatinib (Tyverb) works by blocking HER2 receptors on cancer cells that trigger their growth. The trial is testing whether adding lapatinib to chemotherapy helps people before surgery for cancer of the stomach. It also wants to find out of it helps to start lapatinib before chemotherapy.

Bortezomib (Velcade)

Bortezomib is a type of biological therapy called a proteasome inhibitor. Proteasomes are substances that help break down proteins. They are in all cells. Bortezomib interferes with the way proteosomes work, making protein build up so that the cells die. Trials have shown that bortezomib also makes cancer cells more sensitive to some types of chemotherapy. The VECarboX trial is looking into how well bortezomib works, with chemotherapy, in advanced stomach cancer that cannot be surgically removed.

Everolimus

The RADR2301 trial is looking at everolimus (also known as RAD001) for cancer of the stomach that has continued to grow despite chemotherapy or has come back after treatment. Everolimus is a drug that was first developed for people who had a heart or kidney transplant. It helps to damp down the immune system to stop the body rejecting the new organ. But we know from research that everolimus may also help to stop cancer cells growing.The aim of the trial is to see if everolimus helps people with advanced stomach cancer.

Heat shock protein inhibitors

Heat shock proteins help other proteins to trigger cancerous changes in some cells. Drugs called heat shock protein inhibitors block the messages from the heat shock proteins. Researchers are seeing whether a heat shock protein inhibitor called AUY922 can help to control stomach cancer that has spread to other parts of the body (advanced stomach cancer). They are comparing AUY922 with the chemotherapy drugs docetaxel and irinotecan. 

You can find detailed information about biological therapy trials for stomach cancer on our clinical trials database. Choose 'stomach' from the dropdown list of cancer types.

Stomach cancer and its treatment usually causes weight loss. People who lose too much weight often find it harder to cope with chemotherapy treatment and may get side effects sooner. So research is increasing into ways of stopping people losing too much weight. Severe weight loss is called cachexia. This is a complex problem that involves changes in metabolism and can lead to muscle wasting.One trial is looking at using the drug thalidomide to help slow down or stop cachexia. There is more information about this trial on our clinical trials database. Type 'thalidomide' into the free text search box.

There is more information about diet problems in the section on coping physically with cancer.