Wednesday 10 March 2010

where do we go from here? Part 3 chemotherapy and other therapies

I've talked about surgery and radiotherapy in the last two blogs, so today I'm looking at the third arm of the tri-modal approach to mesothelioma treatment - chemotherapy: the use of anti-cancer or "cytotoxic" drugs to destroy cancer cells.  I'm also going to run through some of the other therapies that are in development, as well as complementary and alternative therapies (CAT). 

Take a deep breath if you intend to go through this lot - it's a lengthy read with lots of weird words that you won't recognise.  However, writing it has helped me sort out a few things in my own mind....

How it works
Cytotoxic drugs circulate in the blood throughout the body, damaging dividing cells, including cancer cells which divide much more often than normal cells.  However, they also affect those healthy body tissues where cells are constantly growing and dividing at a fast rate, such as skin, hair follicles, bone marrow and the lining of the digestive system, which explains the side effects of chemo.

The standard treatment
The most commonly used combination of chemo drugs for pleural mesothelioma are pemetrexed (brand name Alimta) and cisplatin.  This is the combination that Steve would have received, had he not taken part in the Velcade drug trial. It is still there "on offer" as a first-line treatment on the NHS, should action be needed to keep Leo under control. However, these two drugs are particularly toxic to the body and Steve has already experienced the side effects of cisplatin.  So, are there alternatives?

Other chemo drugs and drug trials
The scientific journal Lung Cancer recently reported (February 2010) the results of an investigation into the possible benefits of a different combination of chemo drugs for mesothelioma patients, pairing pemetrexed with a different drug, carboplatin.  Based on a study of 49 patients, the majority reported a benefit after two cycles of treatment and also reported that toxicity was relatively low.  The median survival rate in that study was 14 months, slightly greater than the comparator group who took pemetrexed and cisplatin, which had a median survival rate of 12.1 month. Whilst not a huge difference in outcome, it seems that this combination may prove to be less toxic and more effective than the usual regime - something worth discussing tomorrow?  

That said, the results of a German study (December 2009) based on a much larger sample found the median survival rate of patients receiving the standard pemetrexed/cisplatin combination to be better than those being treated with carboplatin/pemetrexed (11.3 months as opposed to 9.7 months).  Not so good news.  However, the ray of hope here is that pemetrexed is effective in those who have already had chemotherapy, albeit to a lesser extent than on patients who had not been pre-treated. It can therefore be used for "maintenance" as well as a "first line" therapy, with potential benefits for someone like Steve.

Another ray of hope for second-line treatment is a drug called Oxaliplatin (AKA Eloxatin).  In 2008, the Journal of Occupational Medicine and Toxicology published research on a clinical trial of 29 patients who had been previously treated with Cisplatin and Pemetrexed.  These patients receiving three cycles of second-line treatment with Oxaliplatin and another drug, Gemcitabine reported partial remission in 6.9% of cases and a stable disease in 37.9% of cases, a control rate of 44%.  Just as important, the patients tolerated the treatment well, with no significant toxicities or side effects.  

Worldwide clinical trails (VANTAGE 14) are now taking place of a drug called Vorinostat (aka Zolinza) as a second line treatment for mesothelioma for patients who have already received pemetrexed combined with cisplatin or carboplatin - one to keep an eye on in the future.

Back in the UK, a Derbyshire man was recently the first person in the world to be given a new drug LDE 225, in a trial being carried out in Leicester, at the Royal Infirmary. The drug targets only cancer cells by cutting off the protein which such cells need to grow and divide.  Although too early to speculate on the effect of the drug, early signs are encouraging. However, to take part in the trial not only must patients be very fit, there must be no other treatment option available - which sounds like it's very much a last not one for Steve, for the time being at least.  

Chemoembolization and hot chemotherapy
I can't ramble on about chemotherapy without referring to chemoebolization, as pioneered for mesothelioma patients by Professor Vogl in the J W Goethe University Hospital, Frankfurt.  Put very simply, this a technique for introducing chemo drugs into the patient's system via a sheath inserted into the femoral vein, which is then pushed forward into the vessels which supply blood to the cancer. This approach concentrates the drugs in the area of the cancer for a couple of weeks, rather than allowing them to roam all over the body via the blood system.  Using this technique, doctors are able to use a concentration of cytotoxic drugs up to 20 times higher than normal, with reduced side effects.  
Debbie Brewer from Plymouth is the living proof that this technique can be very effective (link to Debbie's blog, mesothelioma and me, on the right).  

We talked about this technique with the Oxford doctors not long after Steve was first diagnosed, but from a position of relative ignorance. The doctor we spoke to did not appear to be aware of it, and dismissed it out of hand when he heard that patients had to pay the costs, saying that proper clinical trials are free.  I think we need to go back tomorrow armed with more information to discuss this approach in greater detail, now we know rather more about that is involved, have the reassurance that it is a bone fide, ongoing clinical trial and in the knowledge that some PCTs have funded at least one cycle of treatment.  

Thermal therapy/chemo-hypothermia
Administering chemo drugs diluted through a drip, directly by injection or indirectly by chemobolization are not the only methods of delivery. Apparently, heating increases the metabolic rate of cancer cells and they are very active sucking up the poisonous chemo drugs.  Based on this, following surgery, doctors sometimes fill the chest cavity with hot chemotherapy to give the lungs a good soak. A similar approach can be taken by heating chemotherapy drugs prior to injection.  If it increases effectiveness of the drugs, I'm not sure why this isn't done as a matter of course.  A question for tomorrow, perhaps?

A recent announcement online that has got the meso world buzzing is a "vaccine" against mesothelioma, which has shown early promise in its first clinical trial. The vaccine is an example of dendritic cell (DC)-based immunotherapy, in which the bodies own immune system is harnessed to target and destroy cancer cells.  It works by taking samples of the patient's own dendritic immune cells, mixing them with proteins from the meso tumour and implanting them back into the body.  There, the mixture activates other elements of the immune system (known as T-cells) and encourages them to attack and destroy the tumour.  

Researchers in the Netherlands used this approach on ten mesothelioma patients and found an immune response in all. After three further injections over a two week period, tests on four of the patients showed that tumours had shrunk. Other than flu-like symptoms which disappeared in 24 hours, there were no serious side effects.  Given the small size of the sample, clearly more testing and research is required before its effectiveness and viability as a treatment has been proven.  But it looks promising....

Other therapies
There seems to be evidence that some families are more likely to develop mesothelioma than others, suggesting that genetic make up could affect your risk of getting mesothelioma.  Gene therapy is one area of research where work is ongoing, but it's in its early days.

Other biological therapies - using substances made naturally by the body to fight cancer - is another area of research actively being pursued.  Some of these therapies work by stopping tumours being able to grow blood vessels, some by blocking the chemical signals that tell cancer cells to grow; other therapies damage the cancer cells direct.  Early trials of a drug called Arenegyer (NGR-h-TNF) suggested that this drug seems to control mesothelioma for a few months and improves survival rates.  It's now moving into phase III trails to see how well it works on a larger sample. The Velcade drug trial which Steve took part in is another biological therapy.  Not long to wait now to see whether that continues to help keep the cancer stable.

Photodynamic therapy (PDT) is a relatively new treatment for some types of cancers. A photosensitizing agent is injected into the blood stream and absorbed by the body's cells, making them sensitive to light.  When the area to be treated is exposed to lazar light, the cells are killed.  This approach has to be combined with an operation to treat mesothelioma. Although PDT has been shown to be safe with other types of cancers, its use in phase I and II trials for mesothelioma has resulted in major complications in a few cases.  Consequently, doctors haven't widely accepted its use for mesothelioma and it's not available in the UK.

Although not part of mainstream medical practice, some meso patients have found complementary and alternative therapies (CAT) useful.  

  • acupuncture, massage and TENS therapy can help relieve pain  
  • meditation can help reduce pain and stress
  • ginger treats nausea and vomiting cause by chemotherapy
  • mistletoe extract (Iscador) is supposed to stimulate to the immune system; it has been used with some success in the treatment of malignant melanoma and breast cancer, and there is a small but growing number of meso patients giving it a go, including Debbie Brewer and Ronny Hill (whose blogs you can access from the links at the top of the page)
  • vitamin C to boost the immune system is controversial - it has been used with good results on cancer patients in some studies, but researchers have been unable to replicate the results in other studies
  • other dietary approaches, including consuming fruit and vegetables daily, eating lean rather than fatty meat, and ensuring antioxidants in the diet are known to reduce stress and improve the body's overall health 
  • herbal remedies such as astragalus and echinacea are also favoured by some - the former is the dried root of a plant native to northern China, used mainly in China to supplement chemotherapy to inhibit the growth of the tumor and decrease the toxic adverse effects of chemotherapy.  The latter you will probably be more familiar with - it's an immune boosting herb which triggers the production of inerferon and, some believe, aids the body to combat diseases such as cancer
  • an extract from the edible mushroom Agarious blazie Murill Kyowa (ABMK) helps to regulate the immune system; it is used widely in Japan for medicinal purposes.  An article in the Journal of Medical Case Reports highlights the case of a 73 year old meso sufferer, whose tumour regressed then completely disappeared following self-administration of ABMK
  • cat's claw (uncaria tomentosa) is a tropical vine native to South America; various studies have yielded inconsistent results, the positive result being for breast cancer
  • ozone therapy - ozone is an activated form of oxygen; there is scientific data that cancer does not flourish in a richly oxygenated environment. However, there is little published literature on the safety and efficacy of ozone therapy in cancer treatment.  A 1991 study found that in combination with a carcinogen, ozone can favour the development of tumours, but ozone exposure following exposure to a carcinogen inhibits tumour development
So there you have it - if you have managed to plough your way through the blog for today and the last two days, you'll know as much about the options as we do.  

Whether we have the opportunity to go through all this at the hospital appointment tomorrow, or whether we will have to ask for a longer time slot remains to be seen....

I can't finish today's blog without sending our love to Felix, Janine and Sam - we are thinking of you all, and keeping our fingers crossed that Felix will make a speedy and full recovery

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