| What's new in mesothelioma |
| Wednesday, January 9, 2008 |
This page is about research into mesothelioma causes, prevention and treatments. You can use these links to go straight to sections on
Why 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. 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, click the button on the left of your screen to 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. Mesothelioma is one of the hardest types of cancers to treat. Progress has been made in treating this type of cancer. But we need to learn a lot more about this disease and how best to treat it.
Until research studies are completed and new effective treatments are found, the treatments covered here cannot be used as standard therapy for mesothelioma.
Causes and prevention
Mesothelioma is most often linked to exposure to asbestos. So much of the research into this disease is based on finding out exactly how asbestos affects the normal cells of the lining of the chest and abdominal cavities. If we can have a better understanding of how asbestos fibres cause cancer and how exposure to this chemical affects us, then we may be able to help prevent the disease. Researchers know that there can be an incredibly long time lag between exposure to asbestos and developing mesothelioma. It can be 40 years or more. This probably meant that it took longer to spot the connection between asbestos and cancer than it otherwise would. But we know now, and the use of asbestos in many countries is now illegal.
There has been talk for the past few years about a link between a virus called the simian virus (SV40) and developing mesothelioma. Some polio vaccine preparations were contaminated with SV40 between 1955 and 1963 and doctors were concerned that people who'd had them may be at increased risk. One large study has indicated that these people are not at an increased risk of mesothelioma or other types of cancers. The study was published in 2003 and found that mesothelioma rates were actually falling in this group of people. If there is a link between SV40 and mesothelioma, it is likely to be much less important that the link with asbestos.
There is some evidence that your genetic make up could affect your risk of mesothelioma. As well as asbestos, exposure to a mineral called erionite is a risk factor. Researchers in Turkey found that in families exposed to this mineral, in some families all the family members developed mesothelioma and in other families, no one developed it. They think that there is a gene in some families in Turkey that increases their risk. (This article is published in The Lancet, volume 357, issue 9254, page 444.) This could explain why some people are exposed to asbestos and do not develop mesothelioma, while others who are exposed do. There is a lot more research to be done before we will know if there are specific gene changes that can increase your risk of mesothelioma. It will be some years after this has been completed before there will be any chance of testing for such a gene.
In the past, asbestos was used widely in the
- Building industry
- Ship building industry
- Manufacture of household appliances
- Motor industry
- Power stations
- Telephone exchanges
There is a study going on in the UK looking at the occupations of men and women and the development of mesothelioma and lung cancer (MALCS). There is information about this trial on our clinical trials data base. Choose Lung: Mesothelioma from the drop down menu of cancer types to find mesothelioma trials.
Finding a tumour marker for mesothelioma
Mesothelioma can be very difficult to diagnose. This is because there are many different types of cells that can make up a mesothelioma tumour. Mesothelioma tumour cells are very similar to some types of lung cancer cells. Sometimes it can be very difficult for a pathologist to decide whether or not the cancerous cells are mesothelioma cells, lung cancer cells or even, sarcoma cells.
To help with diagnosis, scientists are trying to find a tumour marker for mesothelioma. A tumour marker is a chemical given off by cancer cells that can be found in the blood and picked up in a blood test. If a definite tumour marker could be discovered for mesothelioma this would be of great benefit for doctors in making more accurate diagnosis of this disease and may also be helpful to monitor the success of treatment.
An Australian paper, published in The Lancet in November 2003, is about this search. The researchers were looking into tests for proteins related to mesothelioma. This is early research, but they have had promising results. In their study, 84% of people with mesothelioma tested positive, compared to 2% with other cancers or other lung disease. In a group of people who had been exposed to asbestos but did not have mesothelioma, 7 out of 40 tested positive. 3 of these 7 developed mesothelioma and another got lung cancer within 5 years of the positive test. None of the 33 people who tested negative got mesothelioma within the 8 years following the study. It may be that researchers can build on this work to develop a test for screening for mesothelioma and tests for monitoring the disease in people who already have it.
Chemotherapy
It has been a major challenge for doctors to find chemotherapy drugs that work well in treating malignant mesothelioma. Many trials have been done using epirubicin, doxorubicin, cisplatin and methotrexate, but no standard treatment has been set. This has led researchers to look at newer chemotherapy drugs in combination with some already tried. Drugs and combinations in trial include
Most studies giving gemcitabine alone have not been successful. A small number of trials using gemcitabine in combination with cisplatin, have produced some promising results. Many doctors now use this combination of drugs to treat malignant mesothelioma. But more trials are needed before it may be considered as standard treatment. There is information on the side effects of gemcitabine in the side effects of cancer drugs page of CancerHelp UK.
In one study 29 patients were given vinorelbine alone, 6 (24%) patients disease improved and 16 (55%) patients disease remained stable. This has led to further trials using this drug. A trial called MS-01 has been comparing active symptom control (ASC) with ASC and vinorelbine and with ASC, mitomycin, vinblastine and cisplatin. This trial has now closed and we are waiting for the results. You can find information about the side effects of vinorelbine, cisplatin, mitomycin C and vinblastine in the cancer drugs section of Cancerhelp UK.
Topotecan and irinotecan have not shown significant responses when given by themselves. But in combination with other drugs, there have been some good results. There was a trial looking at irinotecan, cisplatin and mitomycin C (IPM). The results were encouraging, but more investigations are needed.
There is information about the side effects of topotecan, cisplatin and irinotecan in the cancer drugs section of CancerHelp UK.
Pemetrexed is a type of chemotherapy drug. It is also called Alimta. It is a little similar to another drug in regular use called methotrexate. It has been used in the largest phase 3 clinical trial ever conducted for malignant pleural mesothelioma. This international trial began in 1998 and results were reported on in May 2002. The study was aimed at finding out whether pemetrexed plus cisplatin was more effective in treating malignant mesothelioma than cisplatin alone. All patients were given supplements of vitamin B12 and folic acid to help reduce side effects (such as diarrhoea). The outcome of this trial was promising. A number of recent trials are now looking at the use of pemetrexed in combination with other chemotherapy agents.
Pemetrexed has now been licensed in the UK for use in combination with cisplatin to treat mesothelioma. This was announced by the company who developed it on 1st November 2004. In August 2005 pemetrexed was approved for use in Scotland by the Scottish Medicines Consortium. In July 2007 NICE (National Institute for Health and Clinical Excellence) announced that they would recommend it for use in England and Wales, for people with advanced mesothelioma which is not suitable for surgery, who are fit enough to look after themselves. Others who are already receiving pemetrexed will be able to continue their treatment while they and their doctors agree that it is helpful. NICE's final decision is expected in September 2007.
There is more about pemetrexed in the question and answer section of CancerHelp UK.
Chemotherapy for controlling symptoms
A trial reported in 2004 on the combination of raltitrexed (Tomudex) and cisplatin. The researchers believe that this combination is better for advanced mesothelioma that cisplatin on its own. But the actual difference between the two groups in this trial was quite small.
Onconase
Onconase is an experimental chemotherapy drug, made from leopard frog eggs. It is not available in the UK. We have included it here because you may have come across information about it on the web. Onconase may have fewer side effects than many other chemotherapy drugs. But not all the side effects may be known as yet. A phase 3 clinical trial has been going on in the USA and Germany comparing the use of Onconase with doxorubicin to doxorubicin alone for people with mesothelioma. Unfortunately, the trial reports aren't very promising. The researchers say that onconase may be better than doxorubicin for some patients, but doxorubicin isn't the chemotherapy drug of choice for mesothelioma now anyway.
Treating fluid around the lung
In mesothelioma, fluid can collect inside the chest. This makes it more difficult for your lung to expand and so it is harder to breathe. Doctors call this pleural effusion. It is usual to treat this by drawing off the fluid and 'sticking' the pleura together. Doctors do this by putting in some sort of irritant, usually bcg vaccine, talc or chemotherapy. You can also treat pleural effusion by operating to remove the pleura (a pleurectomy). This is called a pleurectomy. There is a trial that is comparing these two approaches to see which is better. While this trial is open and recruiting patients, it will be listed on our clinical trials database. To find it and other trials, go to the database and choose 'lung - mesothelioma' from the drop down menu of cancer types.
Surgery
Major surgery for people with mesothelioma has not always been thought a good idea by surgeons. This is because surgery cannot cure the disease. And because many people with mesothelioma are not fit enough to get through a very large operation. But the point of surgery in mesothelioma is to slow the cancer down, rather than cure it. The operation that can be done to remove mesothelioma is called an extrapleural pneumonectomy (EPP). This means removing the lung and the lining of the chest cavity (the pleura) on the affected side. It may help people to live more comfortably for longer. But this has to be tested because, on the other hand, it could mean that having such major surgery means people die sooner than they would have.
In 2001 a programme was started in the UK to look at patients with mesothelioma and see who would benefit most from this type of surgery. 45 patients have been evaluated and 21 patients have been operated on. Of these patients, so far 16 of these patients (about 75%) have lived for at least 6 months and 13 of them have lived for at least 12 months (about 60%). This programme has led to a trial called 'MARS' which opened in 2005. The MARS trial is looking at the benefits and risks of EPP for mesothelioma patients who have had chemotherapy. Results from some studies in the USA suggest that giving a course of radiotherapy after the EPP will help to keep the disease under control for even longer. Some patients in the MARS trial will have an EPP operation combined with radical radiotherapy. Others will have other treatments, such as radiotherapy or less major surgery. There is more information about the MARS trial on our clinical trials database. Either follow the link or click on the blue button to the left of your CancerHelp UK screen. Then choose lung, and select mesothelioma, from the drop down list of cancer types.
Gene therapy
There are a number of new types of treatments being researched that can be put under this heading. Some doctors and researchers are now calling this type of treatment 'molecular therapy', which is a more general term including research into
By studying how changes in these genes cause normal cells to become cancerous, scientists aim to eventually develop gene therapy where damaged genes in the cancer cells can be replaced with normal ones.
The main focus of gene therapy research for mesothelioma involves injecting a virus that has been modified in the laboratory. The virus is injected into the pleural space in your chest, where mesothelioma develops. The idea is that the virus infects the mesothelioma cells with a gene. The gene makes the cancer sensitive to a specific drug that will kill the mesothelioma cells. Without the virus carrying this gene into the cells, the drug would not usually kill them. Much gene therapy research is still centred on how to get the virus into the cancer cells reliably and it will be a while before we will be able to see whether this will develop into a useful treatment. We don't know of any current mesothelioma gene therapy trials that are open and recruiting patients in the UK.
Anti-angiogenic therapy
Angiogenesis means growth of new blood vessels. As they get bigger, cancers need to grow their own blood vessels. Without its own blood supply, a cancer cannot continue to grow. Two of the most important chemicals controlling blood vessel growth are called vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (FGF-2). People with mesothelioma have much higher levels of VEGF than people with any other type of cancer. If the VEGF can be blocked, this could control the growth of blood vessels supplying the mesothelioma tumours. This treatment is a type of biological therapy. These are treatments that use natural body substances (or drugs that block them) to treat cancer. There is more about biological therapies in our cancer treatments section. A drug called bevacizumab is a treatment that stops production of VEGF.
Bevacizumab has been studied in a number of cancers, including mesothelioma, and bowel, kidney, breast, ovarian, non small cell lung, and prostate cancers. One trial recently reported that this drug may increase survival for patients with lung cancer. An American phase 2 trial tested bevacizumab for mesothelioma, in combination with the chemotherapy drugs gemcitabine and cisplatin. This trial closed in 2005, and we are waiting for the results.
Bevacizumab is still very experimental and much larger trials are needed before we will know how effective it will be in treating mesothelioma and other types of cancers.
Immunotherapy
Immunotherapy is treatment with natural substances that the body uses to fight infection and disease. Immunotherapy works by encouraging the body's natural defence system - the immune system - to attack cancer cells. Immunotherapy is really a type of biological therapy. These are a group of treatments that use natural body substances (or drugs that block them) to treat cancer. There is a separate section about biological therapy (including immunotherapy) in CancerHelp UK.
The types of immunotherapies being researched for mesothelioma include
Interferon and interleukin 2
Two types of immunotherapy in trials for mesothelioma are interferon and interleukin-2 (also called IL-2 or aldesleukin). Interferon has been used in trials both on its own and in combination with various chemotherapy drugs. The results of the combination treatment haven't been any better than the chemotherapy drugs on their own. More trials have to be done before we know how useful interferon will be in treating mesothelioma.
IL-2 is made naturally as part of the body's immune response. But now it can be made in the laboratory and used in much larger quantities as cancer treatment. IL-2 can be injected directly into the pleural cavity (intrapleurally) or into the bloodstream. Clinical trials using both these methods have shown some success in stage 1 and 2 mesothelioma. Unfortunately most mesothelioma patients are diagnosed at a later stage than this, when this treatment is not very effective.
Photodynamic Therapy (PDT)
This is a relatively new treatment that is used for a few types of cancers. In PDT, a drug called a photosensitising agent is injected into the bloodstream and absorbed by the body's cells. The drug makes cells sensitive to light. When the area to be treated is exposed to laser light, the cells are killed.
PDT has to be combined with an operation to treat mesothelioma. This has been tried for early stage mesothelioma. The photosensitising drug is injected into your bloodstream a few days before surgery. During surgery, the surgeon then shines the laser light directly onto the pleura.
PDT has been shown to be a safe type of treatment with other types of cancer. But in phase 1 and phase 2 clinical trials for mesothelioma, there were some major complications on a few occasions and so doctors have not widely accepted this treatment। It is particularly likely to be risky when used with major surgery and this combination of treatments is not available in the UK. There are no claims that this treatment will cure anyone of mesothelioma. It is very experimental. We have included it here because it is something you may have read or heard about.
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