Bisphosphonates and side effects

It's generally accepted that bone tumours - whether from primary tumours like osteosarcoma or from metastatic disease - are hard to deal with. Bone cancer pain is difficult to control, and bone tumours can cause fractures and other significant problems, so finding a way of controlling these tumours is essential. To this end there is a whole class of drugs called bisphophonates which are emerging into general oncological practice. These drugs have been found to be effective in slowing the spread of bone tumours, and in helping deal with the pain that they induce. In terms of primary bone cancers, a number of trials are on-going in which these bisphophonate drugs are being used alongside the standard treatments for osteosarcoma. And, as an added bonus, there is evidence that the newer bisphosphonates such as zoledronate and ibandronate, have direct anti-tumour and immune-boosting effects too.

However, there is a big risk that comes with these drugs, which originated as treatments for osteoporosis, and that is a condition called osteonecrosis of the jaw (ONJ). This condition, which occurs in a small subset of patients can cause severe lesions in the jaw, and which can, in a very few cases lead to the crumbling of the jaw. To date there has been no way of knowing which patients are likely to get ONJ, which is a worry for patients taking them, and of course a concern for doctors who prescribe them.

But there may be some good news on the way. Researchers at the Columbia University College of Dental Medicine have done an analysis of patients who developed ONJ, looking at whether or not there is a genetic component to it. And it does appear that this is the case, with variations in a gene called RBMS3 being associated with the occurence of ONJ. This means that in time a genetic test will become available which will help doctors predict which patients are more or less likely to develop ONJ. If it means that doctors will become more confident in prescribing bisphosphonates to cancer patients who need it, then that's really good news.

For more details see the paper here: http://www.ncbi.nlm.nih.gov/pubmed/22267851.

Li Fraumeni Syndrome - New Surveillance Protocol

Many people who have Li Fraumeni Syndrome (LFS) or other TP53 abnormality are often diagnosed when they are suffering cancer - sometimes for the second or third time, as happened with our son George. They are in the thick of cancer treatment and are focused on the immediate problems at hand. However, for people who are not suffering from cancer, a diagnosis of LFS or other TP53 abnormality is likely to be a huge shock. All of a sudden the future becomes uncertain and frightening. The stress is immense.

The answer to the obvious question of 'what happens now?', is most often a variation on 'wait and see'. Currently, in the UK at least, the key thing is to put in place a system in which any LFS patient gets high priority should symptoms crop up. No waiting around for appointments for investigations, no hanging around while one doctor after another mulls things over.

However, a team of doctors in Canada and the United States have trialled a more active program of clinical surveillance. This program consists of regular blood tests and scans, trying to catch things before they become symptomatic. This is a major step forward for LFS patients.

I have written about it on the George Pantziarka TP53 Trust website here: http://www.tp53.co.uk/index.php/lfs-surveillance-protocol

It's required reading for anyone interested in TP53 and Li Fraumeni Syndrome. If you are a sufferer it's something you really need to know about, and, just as importantly, it's something that your doctors need to know about too.

No To The US Research Works Act

Access to information is essential to patients and doctors researching different medical conditions, including cancer. Journal papers offer the latest thinking on disease progression, reports of investigations in fundamental biology, new drugs, clinical trial results and so on. For those with chronic or life-threatening conditions, medical research offers the hope of new insights, new treatments and greater understanding. And, as I’ve written before on this site, access to medical research should be free to all, especially for the research that we – as citizens – have paid for through our taxes.

However, free and open access, as enshrined in the policies of the National Institutes of Health in the United States, conflicts with the commercial interests of the journal publishers. These companies make a lot of money by publishing scientific journal. The subscription fees for journals run into the thousands of dollars a year – way beyond what we as patients and their carers can afford. But the journals make money because university and medical school libraries, private companies and so on subscribe to them. An increased move to open access threatens this source of income.

So, the journals are fighting back and in the US there is now a Research Works Act being considered. This would basically take the publicly funded research results that are published by the NIH and open access journals back behind a paywall. No more free access to the latest information. If you want a particular paper you’ll either have to gain access to a university library or else pay the fees to access the paper (and fees range upwards of $30 per article).

If this Act goes ahead it will be a real loss. It will also be a grave injustice. For tax payers it will mean they are paying twice – once for the research to be carried out, and again should they want to read the results for themselves. But it will also mean denying access to potentially life-saving research to cancer patients at a time when they need it the most.

This site gets a lot of traffic from the United States. Please, if you are a US citizen please act now to stop the Research Works Act from becoming law. Write to your representative, write to your local newspaper, and if you are a scientist or doctor then please write to your professional association or society to take a stand in defence of patient rights.

An Invaluable Service by Irene Pantziarka

When entering the unknown world of watching your child slip slowly on to the path that leads towards death and the finality of non-existence, there is little comfort to be found, particularly if you are an atheist. Consequently, any support that can be identified, which enables you to go on and face each day, making the most of every moment that your son or daughter is still with you, becomes a lifeline. 

For our family, such support came in the form of the paediatric outreach nursing team (PONT) from our local hospital (Kingston). This is a team of nurses who, as the title suggests, visit families in the community, providing certain nursing services for sick children. This means that families do not have to journey to hospital every time they need for example a dressing changed or a line flushed. The nurses work around the family’s schedule. They disrupt family routine as little as possible, fitting in with your convenience, rather than expecting you to fit in with theirs. This is in great contrast to the experience of being in hospital, where almost everything seems to be done at the hospital’s convenience and patients can wait endlessly, with no apology given. In other words, the PONT service is family-centred and providers of other hospital services could learn a huge amount from them. 

I cannot stress enough the value of this service to families like ours. The PONT figured in our lives from the beginning of George’s treatment – changing dressings, flushing lines, offering help and advice – but it was during the final stages of our son’s cancer that their presence became invaluable.

TP53 Forum Now Open

We have previously mentioned the founding of the George Pantziarka TP53 Trust, the first group in the UK dedicated to Li Fraumeni Syndrome (LFS) and other TP53 disorders. The trust is named in honour of my son, George, who passed away in April 2011 after battling with his third cancer, an osteosarcoma of the mandible. The work to set up the charity is proceeding, and I am pleased to announce that the website for the trust is now live at:

http://www.tp53.co.uk

Part of the site is the forum, which is we hope will become central to the trust. If you or your family are affected by Li Fraumeni Syndrome or other TP53 disorder please visit the forum, register and introduce yourselves. As a community people with LFS and other TP53 disorders are isolated and underserved, together we can work to change that.

Q&A With Dr Stefano Fais - PPI and Cancer

In a previous article I highlighted some recent results of the work of Dr Stefano Fais and his colleagues in using the over the counter gastric acid treatment lansoprazole to stop tumours becoming resistant to chemotherapy. Lansoprazole is one of a family of drugs called proton pump inhibitors (PPI), that are targeted at highly acidic environments in the body - and tumours, as is well known, create very highly acidic microenvironments. As chemo-resistance is a major problem in oncology, leading to treatment failure in many patients, this is important work. Kindly Dr Fais has agreed to answer a few questions for anticancer.org.uk:

PP: Why is it important to focus on the tumour microenvironment?
SF: Because malignant cells are progressively selected within the tumor mass for their ability to survive in a very hostile microenvironment, an environment that is generated by their own metabolism. In fact, in the same microenvironment either normal cells or more differentiated cells usually die. Tumor cells survive thanks to some mechanisms them  to quickly eliminate toxins, which would otherwise be able to kill them if they were free to accumulate.

PP: What has been the pre-clinical experience with PPI treatment and cancer in people?
SF: Proton pump inhibitors actually block a mechanism that on one hand induces acidification of extracellular environment, in turn impairing both the body’s reaction to the tumor and also highly reducing the efficacy of drugs that are neutralized by the acidic microenvironment. In fact, pre-clinical data have shown that PPI can increase the efficacy of current anti-tumor therapies and induce a real anti-tumor effect by depriving tumor cells of a key survival mechanism.

Lansoprazole and resistance to chemotherapy

For this first post of 2012 I want to start on a positive note by highlighting an interesting and relevant piece of research from Italy. Chemoresistance is the term used to describe the process whereby cancer cells become resistant to chemotherapy. Unfortunately this is a serious and widespread problem, right across the spectrum of cancer types. Tumours that regress quickly from the initial rounds of chemo, sometimes shrinking away to nothing almost, suddenly seem to bounce back, growing again and shrugging off repeated rounds of the chemo that seemed to knock them out. In many cases these resistant cancer cells become ‘multi-drug resistant’, which means that second and third line chemotherapy treatments also have little or no effect. So, finding a way of reversing this resistance is an important aim in cancer research, and one which is clinically relevant across most kinds of cancer.

It’s this problem that a team of researchers and clinicians in Italy have tackled in a clinical trial. Building on work previously done in the laboratory, Stefano Fais and his co-workers carried out a clinical trial on cats and dogs (now called ‘companion animals’ rather than pets!) with cancers that were resistant to standard chemotherapy. Don’t for one minute think that because the patients were animals that this is not relevant research. Cancers in cats and dogs are much closer to human cancers than cancers in rats and mice. In some types of disease, such as osteosarcoma, the disease acts in exactly the same way that it does in people, and is treated with the same drugs and treatments.

These animals were treated with the common anti-acid drug lansoprazole at high doses – a drug that is available over the counter in the UK – along with the chemotherapy drugs that often fail due to the development of chemoresistance. The response of these animals was compared to another set of animals that had the conventional chemo-only treatment (it was the owners of the animals who decided to stick to the conventional treatments only).

The results were very clear. In the lansoprazole treated group, more than two thirds of animals showed partial or complete responses, compared to 17%of animals in the chemo-only group who showed short-lived partial responses. What’s more, even in the non-responders in the lansoprazole group, the owners of the animals indicated that their pets showed improved quality of life – less pain, less weight loss, greater agility etc.