Chemo, Radiotherapy and Fasting

A while back I wrote about some work by Valter Longo and his colleagues looking at the effects of short-term fasting on cancer progression (here: http://www.anticancer.org.uk/2012/02/fasting-and-chemotherapy.html). They showed that short term fasting can slow tumour progression in a range of different cancer types and can sensitise tumours to standard chemotherapy drugs. While this work was performed in mice, it was solid research that is already being followed up in a number of clinical trials.

In the latest update to their work, Dr Longo and his team report that short term fasting also helps to sensitise cells to radiotherapy. This time the work looked at gliomas - aggressive brain cancers - again in mice. This time they looked at how the standard treatments for gliomas, including glioblastoma multiforme, were improved by the adoption of short term fasting. Both chemotherapy (Temozolomide) and radiotherapy had improved responses in those mice subject to complete withdrawal of food for short periods (48 hours) compared to control groups.

These results are in mice, but again there is no reason why they should not apply to people. Though whether there is the same degree of response is an open question which can only be answered through clinical trials.

For the moment this is yet another small step forward and confirms once again that cancer is more than a disease of delinquent cells, and that disordered metabolism is a key feature with clinical significance.

For those wanting the full details of this new research, it has been published in the open access journal PLOS One: http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0044603

The final word has to be this. If you're a cancer patient and want to try this out for yourself, make sure you talk to your oncology team to ensure you get the support you need.

SIGNIFY - New UK LFS Study

I am happy to be in a position to confirm that a new UK study will look at active surveillance for Li Fraumeni Syndrome patients. The SIGNIFY study, which is now at the final stage of approval, is being run by the Institute of Cancer Research and will initially be available at two centres, Manchester and the Royal Marsden. The protocol will look at the effectiveness of annual whole body and brain MRI scans in confirmed LFS patients. A secondary part of the study will look at the psychological impact of screening.

Recruitment to this new study hasn't started yet, and there is a possibility that it may change slightly before it gets complete approval. As soon as the trial is confirmed and we have some more concrete information details will be posted here. The people running the study are in touch with the George Pantziarka TP53 Trust and will keep us informed.

Aside from anything else, this is a good example of how the forum on the Trust's web site is turning into a valuable tool. The first mention of the proposed trial surfaced there last week, and now we have official confirmation. Thanks to all those who first raised the alert.

Peripheral Neuropathy and Chemotherapy

Side effects from chemotherapy can often be worse than the symptoms of cancer itself - as many patients know, and as we know from our experiences with our son George. For taxane-based chemotherapy, such as Taxol, Paclitaxel and Docetaxel (which is one of the drugs that George had), one of the worst side effects is called peripheral neuropathy. This involves nerve damage, particularly in the hands and feet. It usually manifests as tingling, numbness, burning or pain, but can also involve blood pressure changes, balance problems, constipation and a range of other problems.

It can be severe, and in our case it got so bad that George ended up having to come off treatment, with disastrous results in the end. Again, this is common, and so-called 'dose limiting toxicities' mean the treatments are scaled back or stopped, even when they are showing some signs of effectiveness. Obviously, finding good ways to stop the side-effects means that patients can continue with treatments, and also their quality of life doesn't descend into misery.

Which makes the results of a recent clinical trial worth noting. This was a randomised placebo-controlled trial - which means some patients got the treatment and some got a dummy pill and then the two groups of patients were compared to see what difference the treatment made. The trial was specifically looking at peripheral neuropathy in cancer patients being treated with Paclitaxel. And the treatment being tested? Omega-3 fish oil capsules three times a day. Yep, good old fashioned fish oils rather than some fancy new drug.

The results? 70% of the fish oil patients didn't get peripheral neuropathy, will in the control group it was only 40% that didn't. Not only that, there was a clear tendency for the symptoms to be less severe in the fish oil group for those patients who did suffer some symptoms.

Given all of the other positive benefits of fish oils, this is certainly a study worth bringing to the attention of your oncologists if you're being treated with Paclitaxel or other taxane-based drug. Let's hope that the trial is replicated soon so that results are confirmed.

Anyone looking for the details should take a look at the (open access) paper reporting the result here: http://www.biomedcentral.com/content/pdf/1471-2407-12-355.pdf

Fighting Cancer?

I've written before about the metaphor of a "war on cancer" - not a phrase I find particularly helpful. One aspect of this "war" is that patients are seen as in a personal battle with the disease. They are in a fight with cancer - the disease is at war with them - and the weapons in that war are toxic treatments like chemotherapy, radiation and radical surgery. I don't think these are useful images and are more likely to inspire horror than hope.

I am reminded of all this by reading a really interesting blog post from a person with Li Fraumeni Syndrome and who currently has a rare form of cancer called Leiomyosarcoma,. The blog is called 'Always Look On The Bright Side...' - and the post on 'Fighting Cancer - A Personal View' is well worth a read.

An Anti-Cancer Polypill

The big health news story of the day is on the report that adoption of the 'polypill' - the proposed pill that combines a statin with three common blood pressure drugs. According to the authors of the study, rolling this polypill out to all over 50s will save tens of thousands of lives (I've seen different numbers in different reports, but they all agree it's a significant fugure). The rationale of the pill is that by taking these relatively cheap and non-toxic drugs lives will be saved by reducing the number of heart attacks and strokes. However, the effect should, in theory, extend to lives saved by preventing cancer. There's pre-clinical evidence that at least two of the drugs - simvastatin and losartan - have cancer prevention properties.

The idea of a polypill is one that I'll be exploring later in the year when it comes to cancer, and specifically for Li Fraumeni Syndrome and other hereditary cancer syndromes. An anti-cancer polypill would take simvastatin and losartan - one half of the current polypill - and add two additional drugs - aspirin and metformin. I believe that such an anti-cancer polypill has huge potential, both for the over 50s and also for people at high risk of cancer, including those who've been treated for the disease and are in remission.

As I said, this is an area that I'll be exploring in more detail in the future, so watch this space...

Dr Helen Hanson

Congratulations to Dr Helen Hanson, who is acting as the medical advisor to the George Pantziarka TP53 Trust. She has been appointed to a post of Consultant at the Royal Marsden Hospital, in London. One of Dr Hanson's plans is to start a specialist TP53 clinic at the hospital. This is a development we'll be following closely, and we'll report back as things develop in the future.

Biomarkers for Osteosarcoma Response to Chemo

Clinical advances in the treatment of osteosarcoma are rare, and as I have highlighted in the past (here, for example), there are no signs of improvements in outcomes in recent years. The standard treatment for osteosarcoma is neo-adjuvant chemotherapy (using multiple chemo drugs) to shrink the tumours and then surgery to remove them. One of the things that we do know about osteosarcoma is that good response to chemotherapy (defined as greater than 90% tumour cell death), is associated improved chances overall survival. In other words the more the tumour is killed by the chemo the more chance there is that the surgery removes it all and that there is a lower risk that it will have metastasised. However, assessing the rate of tumour kill is hard to do - at the moment you actually need to remove a sample of the tumour to analyse it. Unlike some other forms of cancer, there are no generally recognised bio-markers that you can use as a way of assessing the success rate during the chemotherapy treatment protocol. Nor is there any way of establishing which patients will respond well to chemotherapy and those that won't.

A just published study has looked at the relationship between the expression of the p16 gene in osteosarcoma and response to chemotherapy. The results were clear - loss of p16 expression in tumours is strongly correlated with a worse response to chemotherapy. This backs up previous work which looked at the relationship between p16 and survival in osteosarcoma. This new study now provides the link to explain this relationship. Lower p16 expression causes less sensitivity to chemotherapy, leading to less tumour cell necrosis and ultimately leading to worse outcomes.

This means that p16 expression can be checked at initial diagnosis and treatment options adjusted accordingly. For patients with high levels of p16 expression then the standard treatments will have more chance of success. For those with little or no p16 expression, other options will need to be considered.

Details of this new study are here: http://www.ncbi.nlm.nih.gov/pubmed/22578565