Friday, 31 October 2014

For The Love of George - Book



The starting point for this blog was a conversation with my son, George, in the middle of his battle with osteosarcoma. I’d had been immersed in reading about treatments, supplements, theories and he thought that it would be good to share that knowledge with other people. We talked about it for a while and he came up with some ideas for a logo, we talked about the domain name and so on. It was typical George, thinking about the future, coming up with plans and schemes. The other web site he was really keen on starting was eat positive, that was one he was really keen on and I’m glad that I’ve managed to kick that off in a very low key sort of way too. Unfortunately not every story has a happy ending, and George did not live to see either of these sites become real. And of course after his death we created the George Pantziarka TP53 Trust to support other individuals and families afflicted with Li Fraumeni Syndrome in the same way that he was.

But for all this activity, I do sometimes worry that people will lose sight of who George was. He was a kid who suffered three different cancers, and who tried just about every treatment available before finally succumbing to the disease at the age of 17. It’s a painful story, but one that is common to families with LFS, or to families with a child with cancer. It’s a story that needs telling. And to that end my wife, Irene Kappes, has written a book called ‘For The Love of George’. I’ll be honest, it’s not an easy read. It doesn’t have a happy ending, though we all hope that what we are doing in his name can make something positive out of what he went through.

We worry that the book is harrowing and will scare some people, but then how can we make clear what families with LFS have to go through if we’re not honest? The only way is to show what George was like. To show what a fantastic kid he was, how we had good times even when the medical situation was grim, and to hope that there things in the book that people can learn from.

A portion of the proceeds from the book will go into the Trust.

The book is available on Kindle and as hard copy from Amazon.

In the UK: Kindle or Paperback

In the US: Kindle or Paperback

Friday, 24 October 2014

Book Review - Surviving 'Terminal' Cancer

Keywords: Cancer, glioblastoma, drug cocktails
Title: Surviving Terminal Cancer
Author: Ben Williams, PhD
Publisher: Fairview Press
ISBN: 978-1477496510

While there are some cancers for which we have made progress in treatments and consequent survival, there are also some for which progress has been pretty much non-existent. Glioblastoma multiforme (GBM) is one of the latter – the survival statistics are abysmal and have remained unchanged for many years. Which is why this book, by professor of Psychology Ben Williams, is so inspirational. When faced with this terrifying diagnosis, he got through the shock and then decided he was going to do more than just sit back and accept the standard of care treatment that was almost guaranteed to fail. Instead he took matters into his own hands and sought out other options, whatever and wherever they might be. He is, therefore, one of the few very long-term survivors of GBM. What is more, he has done more than just seek out something for himself, and he has dedicated the last twenty years to helping others do the same. This book is his story and it is, without doubt, one of the most inspirational and yet practical books in the vast literature of cancer.

Written in three sections, ‘Surviving Terminal Cancer’ is more than just a memoir, it also includes a section on the need for change in the system of clinical trials and drug development and a final section on some of the specific treatments and supplements that Williams has found to be useful. In all this is a comprehensive range of material that moves far beyond a memoir and becomes more of a manual for the activist patient who wants to go beyond what the standard treatments.

The book starts, however, with Ben William’s own story. He describes the terrifying diagnosis and his initial shock and paralysis in the face of it. But this changes as he responds by using his skills as a scientist to understand the disease and to look at what was being researched. Over time he expands this to develop an approach to his treatment that incorporates multiple additional treatments over and above the standard treatments in place. In the process he comes face to face with an oncological community unwilling to experiment or offer additional choices even when they know that outcome will be dismal. If people are going to die then why is it unethical to treat them with non-standard drugs?

The memoir is profoundly moving and also disturbing in that it reveals a degree of conservatism in the oncology profession that does no favours for patients. 

The next section of the book picks up on many of the issues that his own direct experience raised regarding medical institutions, clinical practice and the clinical trials process. The issues raised are not unique to Ben Williams, nor specific to glioblastoma or even cancer in general come to that. The system is clearly not optional, and it actively inhibits change. It is a system designed for regulators and bureaucrats and the needs of patients are low on the list of priorities. The clinical trials process in particular has continued to evolve towards very large Phase III trials that are expensive, time-consuming and often lead to minor incremental changes in outcomes, if at all. Ben Williams does not argue for doing away with trials completely, instead he argues for smaller and more focused trials leading to changes in clinical practice in a way that is more responsive to good results.

In the final section of the book – suitably entitled ‘What your oncologist won’t tell you’ – the attention turns to ‘alternative’ medicine, supplements, and the current state of play in cancer research.  The arguments about what counts as ‘alternative’ are well-rehearsed, and there is an examination of some well-known controversies regarding laetrile, iscador, the case of Stanislaw Burzynski. The pros and cons of each are discussed, in some detail with regards to Burzynski, but what is more important than the details of each is the process of sifting out the details that Ben Williams goes through. In a world where there are numerous scammers promising miracle cures, arming people with the tools to recognise junk science is essential.

In all this is a fantastic read. It’s thought-provoking, polemical, honest and hopeful. What is more, the approach that Ben Williams is suggesting applies to more than glioblastoma and other brain tumours, it applies across the board to cancer.

Thursday, 2 October 2014

Fecal Transplants And Cancer

Fecal transplantation is probably one of the most disgusting medical procedures in existence. It literally means taking a sample of fecal material (poop, in other words) from one person and transplanting it into another. Like I said, it's a pretty disgusting idea, but one that is receiving increasing attention. The more we learn about the role of our gut bacteria the more we understand that having a healthy gut ecosystem is essential to health. Gut bacteria play a big part in how we digest our food, with possibly a role in causing obesity, and in the development of our immune systems. It's the latter that has been explored the most in inflammatory bowel diseases - which is where fecal transplants have been used to treat conditions like Crohn's Disease and similar conditions.

When it comes to cancer there is also a possible role for our gut bacteria. I have previously written about the study that showed mice with a genetic predispostion to cancer and fed with a probiotic had fewer tumours and later onset of disease than similar mice not fed probiotic. Note that these mice were developing breast cancers, not colon, so the effect of feeding probiotics was systemic, not just restricted to the colon. This is really a stunning result and worth taking note of. But I think there is room to take this further...

There is now strong evidence that our gut bacteria are essential for a good response to chemotherapy - again this has been something of a surprising result, but the evidence is that without the right gut bacteria chemotherapy response is severely blunted. And we also know that having the wrong bacteria - gut dysbiosis in the terminology - is also associated with the development of colon cancer.

Where am I going with this? Well, if we know that fecal transplants can be effective in inflammatory bowel conditions, and we know that gut dysbiosis is a factor in colorectal and other cancers, then shouldn't we now be considering looking at fecal transplants as a possible cancer treatment?

Thursday, 25 September 2014

Nitroglycerin and cancer drug therapy

Following on from the paper on the anti-parasitic drug mebendazole (which I first discussed on this site a while ago) and the antacid cimetidine (paper not yet published), I've been working on another ReDO paper on the drug nitroglycerin. Like all the repurposed drugs we're looking at in the ReDO project this one is commonly used clinically for non-cancer uses, in this case it's a drug used to treat heart problems and blood pressure. Available as tablet you stick under the tongue, or a spray or even a transdermal patch, nitroglycerin is a drug that has been used for over a 100 years as a vasodilator - in other words it relaxes the blood vessels. It's partly this property that makes it interesting in terms of anti-cancer treatment.

Like other tissues, tumours need a blood supply for food and oxygen, and it is well-known that they release chemical signals that cause new blood vessels to form. This is the process called angiogenesis, and for many years scientists have been looking at ways to disrupt the process - with drugs like avastin (bevacizumab) developed to stop this happening. The idea is that with no blood supply tumours can't grow. However, even when angiogenesis does take place and tumours sprout the blood vessels they need, the vessels that are formed aren't normal. The blood supply is chaotic and the vessels are much leakier than normal. Back in the late 1980s some scientists started looking at how we could use this to our advantage. The idea is that you take advantage of the leakiness by using drugs that leak out into the tumours rather than spreading throughout the body (as normal chemo does). Hiroshi Maeda and his co-workers termed this the 'enhanced permeability and retention' (EPR) effect.

Nitroglycerin enters the picture as a way of making the leakiness worse by relaxing the blood vessels, thus encouraging large drug molecules to leak into the tumours. And once they've leaked out, the chaotic structure of the vessels means the drugs are retained in the tumour where they can have an effect. It is, in theory at least, a way of targeting anti-cancer drugs to the tumours and not to the rest of the body. It's an elegant idea and has lots of experimental evidence going for it. And the evidence includes some small trials in humans - primarily in lung and prostate cancers. There are more clinical trials on-going, and we can but hope that their results encourage more work in this area. To really work well we need to team up the nitroglycerin with some reworked chemotherapy drugs that are specifically designed to work with the EPR effect.

Friday, 19 September 2014

Gina Pantziarka 1964 - 1994



Everyone has a cancer story. Mine started in the summer of 1994. My wife, Gina, had given birth to our second child – George – a year previously and had been suffering a bit from the blues. She’d been feeling tired, low, generally out of sorts. It was hard to pin down any particular thing that was wrong, she just felt exhausted all the time and there were these odd symptoms that seemed to come and go. For example her menstrual cycle seemed to be out of whack, or at least there were a couple of times when there were unexpected bleeds mid-cycle. Was that the sort of thing that happened after giving birth, didn’t it just take time for things to settle down again? In any event a couple of visits to the GP didn’t suggest anything other than a mild bout of post-natal depression. In the summer we were due to go on holiday to Cyprus, it was where she was born and we always holidayed there so that she could get to see her parents and her sister.

Normally she really looked forward to going on holiday, but this time she was just feeling worn down. Something wasn’t right, but she was only 29 years old and had no history of illness. She’d put on a fair bit of weight in the previous few years but other than that there was nothing to cause concern. A week before we were due to leave I suggested she go back to the GP and explain what was going on. The doctor seemed to be a bit perplexed and hesitant and suggested that some investigations might be in order. It was all a bit tentative. How urgent should these investigations be? Gina wasn’t really sure how concerned the doctor was, so I called the GP to ask the question directly: did we need to postpone our holiday? And the answer was clear enough, there was no reason not to go on holiday.

We spent two or three weeks in Cyprus. Gina’s parents were over-joyed at their new grandson and thoroughly besotted with their grand-daughter, now seven. It was a tiring holiday in many respects. We did a grand tour of family on both sides and for a while Gina seemed back to her old self – always smiling, chatting and enjoying company. Towards the end the tiredness was edging forward again, not that she complained much, though she did let on to one of her cousins that it had been a bad year so far and she couldn’t wait for it to finish and a better year to start.

Thursday, 11 September 2014

Report from Metronomic Chemotherapy Conference



Chemotherapy remains at the core of much current cancer treatment. Along with radiotherapy and surgery, it’s one of the big three that nearly every cancer patient has to face in the treatment of disease. Many of the ‘classical’ chemotherapy drugs have been in clinical use for decades now, and you would think we would know all there is to know about how best to use them. Unfortunately it appears not... 

The most common approach to chemotherapy is the multi-drug maximum tolerate dose (MTD) protocol. Here you take a set of drugs that work in slightly different ways and then blast them into the patient in a fixed pattern and at the highest possible dose. These cocktails are incredibly toxic – they knock out cancer cells but at considerable collateral damage. Patients lose hair, suffer sickness, loss of immune system, suffer damage to the heart and other organs. It’s a horror and nobody looks forward to chemo. On the plus side there is often a considerable amount of tumour kill, at least at the beginning. But very often tumours develop resistance, the drugs stop being effective and the side effects continue.

However, there is an alternative approach to using these drugs called metronomic chemotherapy. This involves giving considerably lower doses of these drugs but much more frequently. Here, instead of blasting the patient with chemo and then leaving them for a couple of weeks while they recover from the blast – time in which the tumour can also recover – you give a steady drip-drip of the drugs instead. The side effects are considerably lower and quality of life is much higher – especially as the drugs are usually given in tablet form on an out-patient basis.

Friday, 5 September 2014

A new surgical technique for bone cancers



When it comes to bone cancers – such as osteosarcoma or Ewings sarcoma – surgical removal of the tumour-bearing bone is part of the standard treatment. Chemotherapy is part of the treatment, and sometimes radiotherapy, but resection of the bone is at the core of any curative program.  In days gone by this used to mean amputation of a limb, but these days a lot of work goes into limb-sparing surgery. And of course for those cases where the tumour is not in a limb, amputation isn’t an option any way.


In practice this means that very often surgery involves not just the removal of the effected bone, but also taking bone from another part of the body and slotting it into place a replacement. In my son’s case, George had three separate operations to treat the osteosarcoma in his jaw. The second and third time the ‘new’ mandible had to be replaced with a ‘newer’ one – in the end bone taken from his leg, his hip and a rib all to craft new jaw bones. While his was an extreme case, it shows what surgeons are capable off – but also gives an idea of how much trauma is involved to the patient. Some of the operations took more than 12 hours to complete. 


But what if there is a way to reduce the scale of the operation? What if the surgeons didn’t need to harvest new bone to replace the diseased one?


Surprisingly, such an approach does exist. It involves removing the diseased bone – making sure there are good margins as normal – and then the bone is treated to definitively kill the tumour cells. This is achieved by placing the resected bone in liquid nitrogen or bombarding it with very high doses of radiotherapy. Then the treated bone, now stripped of disease, is replaced in its original position. No need therefore to operate on other parts of the body to harvest bits of bone. No need for extensive remodelling.


Does this radical new treatment work? Recent papers show that the results are very good – there are lower rates of complications, low rates of disease recurrence, and of course lower risks of infection and faster recovery times.  For example in one study, published in the Bone and Joint Journal (http://www.bjj.boneandjoint.org.uk/content/96-B/4/555.abstract), no recurrences are reported at all in the grafted bones. 


That’s the good news. For patients in the UK the bad news is that this procedure, which was first used in Japan about 10 years ago, is not available. I remember asking for this for George, but got a blank look in return. So far as I know this is still not available in the UK – though I’d love to find out that someone, somewhere in the NHS has started doing this. It would make a huge difference to those people who’ve got primary bone cancers or bony metastases.