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Pancreatic cancer research

All treatments must be fully researched before they can be adopted as standard treatment for everyone. This is so that we can be sure they work better than the treatments we already use. And so we know they are safe.

First of all, treatments are developed and tested in laboratories. Only after we know that they are likely to be safe to test are they tested in people, in clinical trials. Cancer Research UK supports a lot of UK laboratory research into cancer and also supports many UK and international clinical trials.

Researchers are looking into 

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Why we need to do 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, researchers develop and test potential new treatments in laboratories. For ethical and safety reasons, experimental treatments must be tested in the laboratory before they can be tried in patients. If we describe a treatment as laboratory research, it is not ready for patients and is not available either within or outside the NHS. Cancer Research UK supports a lot of UK laboratory research into cancer.

Tests in patients are called clinical trials. Cancer Research UK supports many UK and international clinical trials.

Our 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 that interests you, 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.

All the new approaches we cover here are the subject of ongoing research. Until studies are completed and new effective treatments found, these treatments cannot be used as standard therapy for cancer of the pancreas.

 

Research into the causes of pancreatic cancer

Researchers are

Trying to find out more about the causes of pancreatic cancer

Cancer of the pancreas is often diagnosed when it is quite advanced and difficult to treat. Researchers want to learn more about why pancreatic cancer starts and what helps it to grow. To do this, there is a trial collecting samples of tissue from people who have pancreatic cancer and from people who don’t. Doctors hope that a better understanding of how pancreatic cancer develops may lead to better treatments in the future.

Looking at the genes of people with pancreatic cancer

A few people are born one step closer to developing pancreatic cancer because they have inherited a high risk faulty gene. Families that carry the faulty BRCA2 gene (known as the breast cancer gene) or a faulty gene called p16 have an increased risk of pancreatic cancer. Some families with a strong history of melanoma skin cancer also have this p16 gene fault, but not all. If we can find out how to identify people at increased risk before cancer develops, they can have regular screening for early signs of that particular cancer.

From the pattern of pancreatic cancer in some families, experts can tell that there is likely to be a gene fault that only affects the pancreas. If you come from a family that carries this gene fault, statistically your risk of getting pancreatic cancer will be higher than it is for people in general. But we can't tell who in these families carries the gene because we haven't identified it yet. The risk will only be high for those family members who have inherited the gene.

Cancers most often develop because cells have developed gene faults during your lifetime, not because you have inherited a gene fault. When genes are faulty, the proteins they tell the body to make are faulty too. An abnormal protein called K-ras, is found in the pancreatic cancer cells of about 95 out of every 100 people diagnosed (95%), even when the disease doesn't run in the family. This may be a clue to how normal cells develop into pancreatic cancer cells. If we can find out how genes have been affected in cancerous cells, this may lead to the development of new treatments, possibly with fewer side effects than current cancer treatments.

 

Screening

Scientists and doctors at Liverpool University are looking for ways to diagnose cancer as early as possible in people at high risk. They know that people who have a family history of inflammation of the pancreas (hereditary pancreatitis) tend to have a higher than average risk of getting pancreatic cancer.

They are running a study called EUROPAC. This is a screening study for people over 40 with hereditary pancreatitis or a significant family history of pancreatic cancer. Significant family history means at least 2 or 3 people diagnosed with cancer of the pancreas on the same side of your family, depending on how close a relative they are and on their age. Sometimes people younger than 40 are considered for the study, depending on their family history.

The doctors in the EUROPAC study are testing pancreatic juice for changes in 3 genes (the genes are called K-Ras, p16 and p53). If any of these genes are abnormal, then you may have a higher risk of getting pancreatic cancer. To get a sample of pancreatic juice, doctors do a test called an ERCP. This stands for endoscopic retrograde cholangiopancreatography. You also have a baseline CT scan or endoscopic ultrasound (EUS) when you join the study. In this study, if your tests show that you have any of these abnormal genes, you will have the tests repeated yearly to check for pancreatic cancer. If not, you carry on having the tests 3 yearly.

Other early research suggests that using EUS and ERCP together can help to find pre cancerous cell changes in people from high risk families. If these tests show that you have pre cancerous cells, your specialist may suggest they remove your pancreas to stop cancer developing. There are some serious side effects to this surgery but the benefits of the operation would nearly always outweigh the risk of pancreatic cancer. More research is needed and at the moment you can only have EUS and ERCP at a specialist centre if you have a very strong family history of pancreatic cancer. These are invasive tests and they can have complications. They are not recommended for people who have an average risk unless they have signs of already having pancreatic cancer.

 

Tests to diagnose pancreatic cancer

Scientists are researching a new test that may help diagnose pancreatic cancer. This is called the Mcm5 protein test. Mcm stands for minichromosome maintenance protein. The researchers have to take a biopsy from your pancreas and test it for this protein. The TRANSBIL study is looking at how reliable this test might be.

The PET PANC study is looking at whether PET-CT scans can improve the diagnosis of pancreatic cancer. This study has closed and we are waiting for the results.

If you are interested in UK clinical trials, look on our clinical trials database. Choose 'pancreatic' from the drop down list of cancer types.

 

Chemotherapy research

The 2 chemotherapy drugs doctors use most often for pancreatic cancer are gemcitabine (Gemzar) and fluorouracil (5-FU). 

A trial called ESPAC 3 compared 5FU with gemcitabine after surgery to remove pancreatic cancer. Chemotherapy given after surgery is called adjuvant treatment. The aim is to try to delay the return of the cancer. There is a small chance that the treatment may stop the cancer from coming back altogether, but this is more unlikely for pancreatic cancer than it is for other cancers. The results showed that the 2 drugs worked equally as well. 

Now the ESPAC 4 trial is comparing gemcitabine on its own with gemcitabine and capecitabine, after surgery to remove pancreatic cancer. Capecitabine (Xeloda) is a tablet form of fluorouracil. The combined chemotherapy treatment is called GemCap.

Doctors in Japan have been looking at an oral chemotherapy drug called S-1 after surgery to remove pancreatic cancer. Studies have found that S-1 appears to be as good as gemcitabine, if not better. There are differences in how different populations break down (metabolises) S-1 in the body and so some people may need lower doses. This may affect how well the drug works. So trials need to take place in Western populations to see how helpful this drug is.

Giving chemotherapy or radiotherapy (or both) before surgery is called neo adjuvant treatment. The idea is that the treatment may shrink the cancer and make it easier to remove with surgery. Several studies have shown that neo adjuvant treatment is helpful for pancreatic cancer. But more research is needed to get a fuller picture of how well neo adjuvant treatment works, and what the best treatment is. The ESPAC-5F trial is looking into this.

A new type of paclitaxel chemotherapy, called nab-paclitaxel or Abraxane, has been looked at alongside gemcitabine in an international phase 3 trial. The doctors compared gemcitabine and nab-paclitaxel with gemcitabine alone in people with advanced pancreatic cancer. They found that the cancer was controlled for longer in the group who had the combination of drugs. The average length of time people lived (overall survival) was 8 1/2 months in the group who had nab-paclitaxel compared to nearly 7 months in the group who had gemcitabine alone. The people who had nab-paclitaxel had more side effects, including numbness and tingling in the hands and feet (peripheral neuropathy) and a drop in blood cells. The combination of nab-paclitaxel and gemcitabine is now licensed in Europe as a first treatment for pancreatic cancer that has spread to another part of the body.

The SIEGE trial is looking at 2 different ways of having nab-paclitaxel with gemcitabine for pancreatic cancer that has spread to another part of the body. The people taking part either have both drugs on the same day, or have nab-paclitaxel 24 hours before the gemcitabine. The researchers want to find out which way of having this combination of treatment works best, and to learn more about how paclitaxel works against pancreatic cancer.

A phase 2 trial is looking at PM01183 for pancreatic cancer. PM01183 is a new chemotherapy drug that affects how cancer cells divide and grow. Doctors want to find out if this drug helps people with advanced pancreatic cancer that has come back or did not go away with chemotherapy. And to learn more about the side effects. This trial has closed and we are waiting for the results.

There is more information about UK pancreatic cancer trials on our clinical trials database. Pick 'pancreatic' from the dropdown menu of cancer types. You should ask your specialist if you are interested in finding out whether you can take part in any trials.

 

Combined radiotherapy and chemotherapy

The chemotherapy drugs used with radiotherapy, for example capecitabine or 5FU, are radiosensitisers. You have them to make the cancer more sensitive to the radiotherapy.

There has been a lot of research into combining radiotherapy and chemotherapy (chemoradiation) after surgery for cancer of the pancreas. Treatment after surgery is called adjuvant treatment. One of the largest adjuvant treatment trials, ESPAC-1, showed that chemotherapy on its own was most helpful after surgery, rather than combination treatment. This led to the ESPAC-3 trial

Other studies have looked at giving the combined treatment before surgery. This is called neo adjuvant treatment. Trial results have shown that this treatment may help to shrink cancers so that they are easier to remove. This is called down staging. Doctors are still looking at the best way of giving treatment before surgery. The ESPAC-5F trial is comparing immediate surgery with chemotherapy or chemoradiation before surgery.

The SCALOP trial looked at GemCap chemotherapy followed by radiotherapy with either gemcitabine or capecitabine for locally advanced pancreatic cancer. Although there was a relatively small number of people in this trial, the results suggest that after initial chemotherapy it may be better to use capecitabine rather than gemcitabine as part of chemoradiation for locally advanced disease. This is because capecitabine had a slightly better outcome and fewer side effects compared to gemcitabine. 

The PERU study is looking at GemCap chemotherapy followed by capecitabine and radiotherapy for locally advanced pancreatic cancer. Half the people taking part will also have the biological therapy drug cetuximab during radiotherapy. This trial has closed and we are waiting for the results.

In 2013, doctors presented the results of an international trial called LAP07. It looked at chemoradiotherapy for locally advanced pancreatic cancer that couldn't be removed with surgery (inoperable). To begin with, the people taking part had 4 months of gemcitabine or gemcitabine and a biological therapy called erlotinib. The people whose cancer was controlled then had 2 months of either more chemotherapy, or radiotherapy and capecitabine together (chemoradiation). The trial team looked at the results after an average follow up of 36 months. They found no significant difference in the average length of time people lived - about 16 months for those who had chemotherapy and about 15 months for those who had chemoradiation. They also found that erlotinib did not improve survival. The trial team concluded that following this trial, standard treatment for locally advanced pancreatic cancer remains chemotherapy. You are likely to only have chemoradiation as part of a clinical trial.

Doctors continue to try to find the best combination of chemotherapy drugs and radiotherapy. You can find more details about trials on our clinical trials database. Choose 'pancreas' from the dropdown menu.

 

Biological therapies

Biological therapies act on processes in cells or change the way they signal to each other. They can stimulate the body to attack or control the growth of cancer cells. There is detailed information about biological therapies in our cancer treatment section. Biological therapies being looked at in pancreatic cancer research include

You can search for UK trials looking into pancreatic cancer on our clinical trials database. Choose 'pancreatic' from the dropdown menu of cancer types. To see all the trials, tick the boxes for closed trials and trial results.

Vaccines

Cancer vaccines are designed to try to stimulate the body's own immune system to fight cancer. The immune system will naturally attack foreign cells that are invading the body, such as bacteria and viruses. Cancer cells are foreign, in that they are not like normal cells. But because cancer cells develop originally from normal body cells, they are harder for the immune system to spot.

The vaccine finds the cancer because it is designed to recognise abnormal proteins made by pancreatic cancer cells. Examples of these abnormal proteins are CEA (carcinoembryonic antigen) and the K-ras protein. The idea is for the vaccine to lock on to the cancer cells, triggering the immune system to attack them.

The TeloVac trial looked at a vaccine called GV1001 for advanced pancreatic cancer. Doctors wanted to see how well it worked with gemcitabine and capecitabine (GemCap) chemotherapy. The trial team found that adding GV1001 to GemCap didn't improve treatment for people with pancreatic cancer.

Another vaccine, called G17-DT, targets a hormone called gastrin, which is normally made by the pancreas. It is also made by pancreatic cancer cells. The idea is that the vaccination with an altered form of gastrin could help to stimulate the immune system to attack the pancreatic cancer cells. But trials of this vaccine have so far shown mixed results.

Unlike vaccines used to prevent infection, cancer vaccines are aimed at treating a disease that has already taken hold. They are most likely to be combined with standard therapies, such as chemotherapy. Removing as much cancer as possible reduces the amount of cancer that the immune system needs to attack. So there is more chance that the treatment will be able to work.

Vaccine treatment is still highly experimental. It is unlikely to be available outside of clinical trials for cancer of the pancreas for some time.

Growth factor blockers

Scientists are doing a huge amount of work into what makes cancer cells abnormal and what makes them grow uncontrollably. They have found that cancer cells make too many proteins that encourage the cells to grow.

There are proteins called growth factors or kinases. And receptors for the growth factors on the surface of cells. There are lots of different types of growth factors and receptors. One receptor that is common in cancer cells is epidermal growth factor receptor (EGF receptor). Different drugs are being developed that block these proteins and receptors. The drugs are named after the type of growth factor or receptor they block - tyrosine kinase inhibitors, protein kinase C inhibitors, or EGFR inhibitors, for example.

Erlotinib (Tarceva) is a tyrosine kinase inhibitor that has been looked at for advanced pancreatic cancer. Results from an international clinical trial showed that people who had gemcitabine and erlotinib did very slightly better than those who had gemcitabine and a dummy pill (placebo), but had more side effects. Another large trial found that erlotinib did not improve survival when added to gemcitabine, compared to gemcitabine alone. 

Other types of tyrosine kinase inhibitor being looked at for pancreatic cancer include vandetanib (Caprelsa) and dasatinib (Sprycel). Researchers for the ViP trial are comparing vandetanib and gemcitabine to gemcitabine alone for pancreatic cancer that cannot be removed with surgery. They want to see if adding vandetanib helps gemcitabine to control the cancer for longer. A different trial is looking at dasatinib with gemcitabine chemotherapy for pancreatic cancer that has spread into surrounding tissue (locally advanced). The researchers want to find out how well the 2 drugs work together and to learn more about the side effects. Both these trials are closed and we are waiting for the results.

An early UK trial is looking at a type of biological therapy called MK-0752. It is a type of notch inhibitor. It works by blocking some of the enzymes needed for cell growth. The trial will be looking at MK-0752 with gemcitabine chemotherapy for people with advanced pancreatic cancer.

Another early trial is looking a new drug called LDE225 with gemcitabine for advanced pancreatic cancer. LDE225 blocks a type of cell signalling called the hedgehog pathway. This pathway can affect the growth of several types of cancer, including cancer of the pancreas. Researchers want to find the highest safe dose of LDE225 you can have alongside gemcitabine and to learn about the side effects of having both drugs together. This trial has closed and we are waiting for the results.

Monoclonal antibodies

Monoclonal antibodies (MABs) are proteins, made in the laboratory from a single copy of a human antibody. They act in the same way as immune system proteins that kill foreign matter when they find it in your body.

When these laboratory made antibodies are injected into patients, they are designed to seek out cancer cells that have abnormal proteins. Several monoclonal antibodies have been looked at for cancer of the pancreas including cetuximab and bevacizumab but the results have so far been disappointing.

However, there is some interest in a monoclonal antibody called ipilimumab. This drug targets a protein called CTLA-4. Ipilimumab stops CTLA-4 from shutting down the immune system. So it may help the immune system destroy cancer cells. Doctors use ipilimumab to treat advanced melanoma skin cancer, and they are looking at it in trials for prostate and lung cancer. Researchers think it may also help people with pancreatic cancer. Early trials in America are looking into ipilimumab alongside chemotherapy for advanced pancreatic cancer.

Immunotherapy

Immunotherapy is another type of biological therapy. It works by encouraging the immune system to attack cancer cells. It may also help chemotherapy drugs work better. Doctors are looking at a new immunotherapy drug called IMM-101 alongside gemcitabine chemotherapy in a phase 2 trial for advanced pancreatic cancer. The main aim of the trial is to compare the safety and effects of gemcitabine and IMM-101 with gemcitabine alone. This trial has closed and we are waiting for the results.

 

Pulses of electricity

This is known as non thermal high energy pulses of electricity or irreversible electroporation (IRE). In February 2013, the National Institute of Health and Care Excellence (NICE) issued guidance on this treatment. The aim of the treatment is to destroy cancer cells in the pancreas by giving short pulses of electricity to the tumour. It does not produce too much heat or cold and so may cause less damage to surrounding tissue.

You have this treatment under general anaesthetic for pancreatic cancer that cannot be removed with surgery. Special needles are put through the skin and around the tumour in the pancreas. Short pulses of electricity fire repeatedly between the needles over several minutes. The doctor may move the needles and repeat the process until the whole tumour and a small area of surrounding tissue is treated. NICE said that it is not clear yet how well this treatment works and there are some risks. So more research is needed.

 

Omega 3 fish oil 

Laboratory studies have shown that omega 3 fish oil may slow down the growth of pancreatic cancer cells and speed up the rate that the cancer cells self destruct (apoptosis). Researchers have also found that the chemotherapy drug gemcitabine worked better against pancreatic cancer cells when patients had omega 3 fish oil at the same time. A phase 2 trial is looking at gemcitabine with omega 3 fish oil for pancreatic cancer that has started to grow into the surrounding tissues or has spread to other parts of the body. This trial has closed and we are waiting for the results.

 

Controlling the effects of pancreatic cancer

Cancer of the pancreas is one of those cancer types that is linked to severe weight loss. It is difficult for people with advanced pancreatic cancer to eat. But there is also an effect of the cancer itself on the way your body absorbs and processes food. There are trials that are trying to find ways to control the weight loss associated with advanced cancer of the pancreas. 

The NUT study looked at giving a nutritional supplement to people having chemotherapy for advanced cancer anywhere in the digestive system. The study did not show improved survival or quality of life for those taking the supplement.

Cachexia is severe weight loss. Cachexia seems to be linked to the production of body chemicals called cytokines. Cancers can produce cytokines in larger amounts than normal. The cytokines can then cause the body to break down fat and muscle faster than normal.

Researchers think that thalidomide may be able to help with cachexia. Thalidomide can reduce the amount of cytokines in the body. So it may be able to slow down, or even stop, the weight loss they cause. Early trial results are promising, but no one is quite sure yet how well it works. Another trial is looking at a new drug called BYM338 to see if it can help build up muscle and stop weight loss. BYM338 is a drug that blocks an enzyme called myostatin. This enzyme controls muscle growth. By blocking myostatin muscle is able to grow. You can find more information about these trials on our clinical trials database. They are not just for those with pancreatic cancer, so are listed under 'all types of cancer' in the drop down search menu.

Another study is looking at the role of exercise in people with lung or digestive system cancer (this includes pancreatic cancer) who have weight and muscle loss. The researchers hope to understand more about exercise in this group of patients so they can design suitable exercises to help people in the future. This trial has closed and we are waiting for the results.

The pre-MENAC study is looking at possible treatments for cachexia. The researchers are looking at a supplement drink, a non steroidal anti inflammatory drug called celecoxib, and advice on exercise and diet. This study has also closed and we are waiting for the results.

Some people with advanced cancer of the pancreas develop severe pain. A trial called NaTTS compared 3 different ways of controlling pain. These were opioid painkillers on their own, opioid painkillers and a coeliac plexus nerve block, or opioid painkillers and an operation to cut the splanchnic nerve. Researchers found no difference between the 3 groups in how well pain was controlled.

 

Pancreatic neuroendocrine tumours

Pancreatic neuroendocrine tumours are uncommon and are treated differently to the most common type of pancreatic cancer - adenocarcinoma of the pancreas. Researchers are looking into chemotherapy drugs, biological therapies such as everolimus, and new types of somatostatin analogues to stop tumours growing. Some researchers are also looking at genes in people with neuroendocrine tumours, which they hope will help them to improve treatments in the future. 

To find UK trials for pancreatic neuroendocrine tumours, you can search our clinical trials database. Click on 'neuroendocrine tumours' from the dropdown list of cancer types.

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Updated: 17 June 2014