Many hearing the news today from the UK High Court that a second judgment regarding the direction that the medical treatment Neon Roberts must be afforded, will be confused as to why the courts are getting involved with this matter. On the face of it, it should be straightforward and Neon should get the standard care that a child suffering his condition, medulloblastoma, should get from the NHS. However, this case is anything but straightforward because Neon’s Mother Sally, doesn’t want her son to receive the ‘standard of care’ (the care which has been demonstrated to be the optimum care possible given the currently available evidence)
Sally Roberts has been quoted as having told the court she believed conventional cancer treatment was "out of date". She said she feared radiotherapy would reduce Neon's IQ, shorten his life, put him at risk of having strokes and make him infertile. It is of course, perfectly normal for Neon’s Mother to worry about the effects of any treatment he may receive but there is something more worrying at play here, which deserves discussing. If these cases end up in the Courts, we all have an interest in this as we, the public, pay for these cases. By the time cases reach the High Court, costs aren’t cheap.
If we look more closely at Sally Robert’s comments we see a worrying aspect to this story. Her comments on the Channel4 news on Friday 22nd December show that she sees the issue as a question of the most appropriate medical treatment for her son. She seems to be questioning the care the NHS wants to offer Neon. Her primary motivation is to care for her son by not exposing him to the side effects that he might arise as a result of medical treatment. This is a caring attitude one might expect from a Mother but it signifies something else, namely Mrs. Roberts’s view of traditional medical treatment as compared to what is known as, ‘alternative’ or ‘complimentary’ treatments. Sally Robert’s said this evening, “I think it’s a very indoctrinated system, we need to explore natural therapies we seem to have ruled out. Chemotherapy and radiotherapy I certainly don’t agree with. I think its out of date.......there are many other ways we could go about this”. She adds, “thousands of children have been successfully treated with other therapies”.
This is the nub of the question that the Judge had to decide on, the wishes of the Mother versus the reality of which medical treatment is appropriate. Overlay Mrs. Robert’s view that ‘alternative therapies’ are preferential and you have the need for the Law to clarify how Neon should be treated. This is a dilemma, which isn’t new. There is a Medical practitioner based in Houston, Texas who claims to have uncovered a treatment to cure brain tumours in patient’s that have exhausted the conventional treatments the US system has in its armoury against disease. The treatment is based upon the Drs belief that his treatment acts upon tumours and kills them offering cures. The clinic espouses the ‘alternative’ treatment in that it lies outside of mainstream medical opinion. There are early stage trials but no end stage studies, which demonstrate that the treatment works in the specific disease. The issue here is that it is very easy for any practitioner to claim treatment benefits without the necessary data to prove efficacy. There is much criticism directed at clinics / practitioners who advocate ‘alternative’ therapies as there is very little credible data to convince medical practitioners that a treatment works. This is the emotional trap that Sally Roberts finds herself in and she is not alone. Its unfair to judge parents like Mrs. Roberts as they are absolutely desperate to find any way of keeping their kids alive. However, the reason the court had to intervene against the Mothers wishes is because there is a moral maze to navigate regarding conventional v alternative therapies. The Courts found that Neon was best served by receiving the accepted ‘standard of care’ despite his Mother advocating ‘alternative’ therapies. The Courts primary interest is that of Neon not his Mothers beliefs in unconventional therapy. This is why we need Courts advise in such matters because they are nearly always dealing with lay people with no real understanding of medicine, physiology or even a basic understanding of how their body works. ‘Alternative’ believers are often well intentioned as they are deeply involved emotionally and nearly always find it impossible to see their way through the issues. This is understandable as they are desperate but the child needs the objectivity that the Court offers as they aren’t best placed to make the judgments. Often these ‘complimentary’ methods are so expensive that parents have to sell their homes and bankrupt themselves to be able to meet the demands of these clinics. The sad reality is that if the best scientific institutions around the world have not been able to replicate the clinical results these ‘alternative’ clinics claim, it is unlikely the claims of these clinics can be substantiated.
This is the sad reality of this situation. Those of us whom work in Health care know the unfortunate outcome of serious disease and its impact upon the families involved. The Neon Roberts case demonstrates the need for intervention from outside agencies, in this case the law, to advise on the best course of action. Despite the best intentions of some parents, they are too close to the situation to be able to make a rationale judgment. In Neon’s case the Law helped make the decision for him. Sadly, many people lose their life savings and assets to cling to hope that their child/relative will find something in these alternative treatments. Until they can demonstrate their value in well-constructed clinical trials, which then get the appropriate approvals, people will need the help of the Law to guide them.
A discussion on ‘Stable disease or ‘disease free state’
Oncology nomenclature seeks to describe different disease states in and around one of the most sensitive and difficult areas of medicine. It is difficult because, despite some staggering progress in patient outcomes in recent years, oncology remains one of the hardest areas to show real progress. The reason for the difficulty in using recognisable terms is because cancer is not one disease but a multitude of disease factors all wrapped up in the term ‘cancer’. The widest dictionary definition of the word cancer is, growth. It is estimated that the physiological processes that combine to create the conditions for tissue to ‘grow’ in an unchecked manner, may number over 200.
When this is placed into context, one can see why cancer is such a difficult physical anomaly to treat. It is amazingly complex and we are still scratching the surface in terms of our understanding of what cancer actually is and how we can treat it.
The unpalatable (for some) truth is that we do not yet know how to cure cancer. The notion of a cure invokes such emotional responses from interested parties, which include patients, friends, and patient groups to name a few. However, the scientific community remains steadfast in its desire to create treatment options that will make a significant difference to patient’ outcomes.
Here is the truth on the global effort to treat cancers. The scientific community’s realistic goal is to, in the short to medium term, turn cancer from an acute disease to a chronic disease. What this means is, as there is no cure for most cancers, the best we can do is to use treatment methods which in combination, slow down the disease process to a pace that makes the condition a ‘long term treatable condition’. The aim is to be able to put ‘brakes’ on the disease to turn into something that can be managed, rather like rheumatoid arthritis. Its not pleasant when somebody suffers but by careful management patients can achieve a quality of life which is something they find an acceptable ‘trade off’ between taking medication and the resulting outcome, whatever the outcomes are.
This has to be seen in context. The most difficult cancers to treat are tricky because they find collateral pathways to continue their ‘growth plans’ (the cancer cell) whatever treatment modality is used, the cancer can eventually find a way to achieve it aim of further replication. This is why survival (termed overall survival in cancer terms) is the Holy Grail of treatment. After all survival is the ultimate measure of treatment success and the ultimate need for patients facing life threatening health issues. Overall survival is an obvious measure of treatment success but as already stated, cancer is a complex disease to manage and sadly, overall survival is infrequently achieved. This means there has to be other measures of clinical outcomes outside of survival because cancer is incurable and we are seeking to ‘manage’ it as best we can. The main treatment milestones in most oncology studies are Survival (OS) Progression free survival (PFS) Stable disease (SD) and Progression (P) An explanation is offered below.
Overall Survival is the time that a cancer patient remains alive as a result of treatment for their disease. (Example shown later) This can vary from a matter of months to years depending upon which cancer is involved.
Progression Free Survival (PFS)
Progression Free Survival is different to Overall Survival. This term refers to the period within a disease journey, where a patient enters a period where they have not achieved ‘cure’ as they still have their disease but as a result of treatment or sometimes naturally, the natural progression of their disease has halted for a period of time where the disease doesn’t get any worse, hence the term Progression Free Survival.
Progression Free Survival is usually a finite period of time within the treatment/disease journey and in most cases, usually ends with signs that the symptoms of the disease return signaling the end of this period (PFS)
Stable Disease is a term, which indicates the state in which a cancer has been treated and clinical signs of disease do not appear to ↑ or ↓ in extent or severity. Stable disease can vary from study to study and ranges from weeks or months to years (infrequently) This term is quite often confusing to lay people but it is a very valuable state to be in if you are a patient undergoing treatment. Patients can gain an acceptable quality of life in Stable Disease during their cancer journey.
Progression is the term used when clinical indicators suggest the tumor is once again active. This means the treatment has either stopped working, or it is still working but the cancer has found an additional pathway to start growing again. This usually means adding further treatment lines or an adjustment to dose. Frequently, progression means that treatment has achieved as much as it can and will probably mean that active treatment is of limited value at this stage.
Objective response rates
This term refers to the % of patients who actually demonstrate a response to any therapy they have been subjected to. Any patient who has demonstrated any type of tumor response has received an Objective Tumor Response. Clearly the higher the percentage figures the more patients will be likely to get a response from the treatment.
Palliation or palliative care
This term refers to the stage where all active treatments have been explored and for whatever reason, have ceased to bring any meaningful value to the patient. Palliation is the managing of patient’s pain and psychological states when active treatment is no longer appropriate.
A properly constructed clinical study in oncology will normally feature these terms as they are the standard terms used to study and determine if a treatment has value. New treatment needs to meet the standards set out in the Study Protocol, which will usually be comparing one drug (an older or contemporary with a new or proposed drug)
If new treatments have not been through this rigorous process they have not shown that any treatment observations were as a result of using the drug as opposed to chance or previous treatments.
Study from ASCO 2012 - Combining chemotherapy and radiation.
One of the pieces of clinical work presented at ASCO 2012 in Chicago last week was this study of patients with Anaplastic Oligodendroglial Tumours. The well respected EORTC demonstrated that chemotherapy after radiation therapy in a specific mutated gene material (1p/19q) located on chromosomes 1 & 19. The study demonstrated that the disease process can be significantly slowed down by the use of this regime and is a further demonstration of the value of ‘gene targeted therapy’. For the patients in the chemo and radiation arm, a progression free survival (pfs) of 2 years was achieved compared with 1 year in the patients receiving radiation alone.
1) Combining chemotherapy and radiation can make a substantial difference to patient outcomes with Anaplastic Oligodendroglial Tumours with a specific gene mutation.
2) 1p/19q is a biomarker which can identify a subset of patients whom can achieve a substantial Progression Free Survival over those patients whom received radiation alone
3) The panel commenting on this study at the ASCO conference commented on this study being ‘practice changing’
The graphic is difficult to read http://www.nejm.org/doi/full/10.1056/NEJMra1204479?query=featured_home&
The chart shows the major oncological milestones between 1984 to date. The pivotal steps in cancer care are highlighted. Of note, there are no references to Antineoplastons as a major breakthrough in metastatic disease. In fact, there is no mention of them per se.
Source NEJ of Medicine
This study found in the Cochrane library http://onlinelibrary.wiley.com/o/cochrane/clcentral/articles/542/CN-00126542/frame.html highlights a Phase I study submitted to the The Kurume medical
journal, a Japanese publication with low international impact. The study was submitted in 1995. Key observations from the abstract are interesting in that it highlights, 'Antineoplaston A-10 and
AS2-1 are less toxic than conventional chemotherapeutics and they were useful in maintenance therapy for cancer patients'. The abstract goes on to highlight,
'The evaluation of the usefulness of the Antineoplastons in combination therapy based on the imaging findings during the course of treatment revealed disappearance or measurable shrinkage of the tumor lasting more than one months as visualized by magnetic resonance imaging or computed tomography was seen in 15 tumors (32.6%). No increase in size of tumor for more than 3 months was observed in 8 (17.4%). The mean survival time of these patients was significantly longer than that in patients with tumors showing progressive increasing (17.52 + 3.31 months vs 4.80 + 0.65 months, p < 0.005). Antineoplaston A-10 and AS2-1 are less toxic than conventional chemotherapeutics and they were useful in maintenance therapy for cancer patients'.
What does the paper really say?
The authors conclude that the side effects were manageable and did not require treatment cessation.
Coverage of the Burzynski Clinic in Houston continues unabated with the debate raging over if, as some Burzynski supporters believe, there is health value to be gained from attending his clinic and following his treatment regimes. In the social media there are many comments expressed regarding the Burzynski movie which seems to have created headlines amongst the non-scientific population
whom desire only to see/hear headlines before making their minds up regarding the validity of the this subject matter at hand (does Burzynski have a cancer cure and has he been the subject of Government orchestrated underhand dealings) The snapshot trailer of the movie above has an advertisement feel to it and the headlines would not be out of place if Grisham had launched a press review of his latest piece of fiction. The sponsors are two media organisations who, some would say, have a vested interest in hyping up the movie for ratings.
The key to how valuable an analysis this movie is of treatment that the Burzynski clinic offers lies buried within the data.
Most lay people will not be a) interested and b) have the knowledge and understanding of medical data to be able to objectively appraise the information contained within the movie. After discussion of the data there is the issue of, as the movie and Burzynski supporters believe, there is a conspiracy to suppress the notion that this lone Doctor has uncovered a ‘cure’ for cancer.
To look at this fairly it requires a discussion about the two points raised (data and conspiracy theories) To summarise this does not do the subject due respect but, mindful of the non-scientific nature of some readers, a summary seeks to merely ‘touch’ upon the data and what it means.
In the developed world, all new medicines are required to undergo a rigorous process of validation to prove, as far as is possible, that the new medicine does in fact do what the developer says it will do and that it can do so effectively and safety. Finally it is the responsibility of the developer to contrast the new treatment with existing treatments which have already been through the evaluation processes as described above. This process usually has 4 stages but the first three are key (Phase I to 3) Essentially Phase 1 data is designed to evaluate;
Phase 1 is concerned mainly about finding a safe dose and an understanding of any side effects associated with the new drug. It is worth noting that 90% of new treatments do not progress to Phase 2 such is the difficulty in proving new compounds have any treatment value.
Phase 2 studies follow on from Ph1 if the analysis of the data encourages further work (i.e. a safe dose has been established with an acceptable safety profile) the purpose of Phase 2 studies is to develop the experimental treatment a little further by seeking to understand a little more about the drug.
Phase 2 studies;
Phase 3 studies
This is an important Phase (probably the most important) as this is where the early work in Phases 1&2 is really put to the test. This is where there are larger patient numbers and a comparator (a drug to compare against the new treatment) is evaluated. Drugs which get to this Phase can still fail. It is only when bigger patient populations are introduced that ‘key facts’ about the experimental drug becomes known. It is largely as a result of the Phase 3 studies that Health Care regulators around the world make their decisions about if an experimental treatment gets licenced for widespread use.
It is worth taking note at this point that most clinical developments (particularly new chemical entities) take about 8-10 years to get to marketing stage (where Doctors are allowed to use the treatment)
If you wish to read a broader description of the clinical trial process, this link takes you to a Cancer charity which explains Cancer to patients
Discussion on Burzynski data
Now that the clinical trial process has been described we are able to view where the Antineoplastons therapy that the Burzynski clinic features in the movie, is in its development and hopefully understand the arguments with a little more clarity.
The Burzynski clinic has completed Phase 1&2 of its clinical trial process. Let’s recap what this means. The new treatment that the Burzynski clinic has been working on has demonstrated to have found a treatment where a safe dose has been identified (Phase1 trial) it then entered Phase 2 trials where the study seeks to understand a little more about the treatment on a slightly larger patient group. The Burzynski clinic has completed the first 2 Phases and now is required to put the treatment to the biggest and most important test by going into Phase 3 studies (the stage where licences are determined) This is by no means approval or permission to be in general use. Remember also that drugs will also fail at Phase 3.
Critics of the Burzynski development of ANP’s point to the fact that after carrying out clinical trials for almost 30 years (this figure is disputed by Burzynski supporters but to be fair, let’s say its 25 years) that key data should now be available. Remember that its takes around 8-10 years to get NCE’s (new chemical entities) to the clinic (where Doctors can use on a general basis) so the question arises, what has been happening in the Burzynski clinic to take this long to prove his treatment works? Critics say that he has had 25 years and has still not proved his treatment works to a level where it can be licenced for widespread use.
Further concern arises from the fact that the Burzynski clinic charges such high fees for inclusion in their clinical trials. Estimates vary but figures of £200,000 ($313,000) seem to be consistent. This is highly unusual as clinical trials around the world do not charge for trials. If they do it is only small fees. We have to ask ourselves the question, why are patients charged such high fees when the treatment has not been proved to work? Remember drugs have to have completed Phase 3 studies to be able to receive a licence. The Burzynski clinic treatment has not completed any Phase 3 trials since it began its clinical trial programme. Burzynski clinic supporters say the fees reflect the fact that the ANP trial programme is self-funded so Dr Burzynski has to charge high fees. Patients have questioned these fees especially as Dr Burzynski is reported to live in a $6,000,000 mansion and makes political donations regularly. Patients also ask, if the fees are so high because of having to self-fund the trial programme, how much money has been paid by patients in the 25 years he has been doing his trials? And why are there no Phase 3 results yet?
The last question is often answered by Burzynski clinic supporters by citing the FDA Conspiracy against Dr Burzynski. They say he is unfairly dealt with and is being supressed in conjunction with what they call ‘Big Pharma’ (major Pharmaceutical companies) to make sure he doesn’t ever get a licence for his Antineoplaston treatments. There is no evidence that can be found to substantiate this claim. In fact, if the Burzynski treatment had shown, through the clinical trial process, that it had enough potential to be used world-wide, a major corporation would have stepped in to fund this by now. For all the negative press that ‘Big Pharma’ receives from the Burzynski clinic supporters, the major oncology companies have a long history of partnering with developers like Burzynski when they can be sure that the treatment has real potential. This appears to be the major problem for the Burzynski clinic. They have not, despite the hype surrounding the movie, been able to show the world via the appropriate clinical trials (haven’t got to Phase 3 in 25 years) that the treatment meets the accepted criteria required for the medical establishment, major corporations as investors, independent patient liaison groups and most importantly the patients themselves to be able to make this treatment available around the world.
Conspiracy theorists will argue that the Burzynski clinic is being supressed at the same time the relatives and patients, desperate for a last chance to beat nature at its own game and gain extra years in the face of a terminal illness, will grasp in their desperation at anything that might give them more time with their loved ones. They will do almost anything to achieve this goal which includes trying to pay fortunes for an experimental treatment that hasn’t, as yet, been able to satisfy the world of its value. It is easily understandable why patients would want and need to believe the contents of the Burzynski Movie. However, as is the case in life, the spirits of the desperate desperately and broken are susceptible to any suggestion they can cheat nature. The Movie doesn’t advance the academic case for the ANP treatment as much as patient’s, carers and the medical world want and need.
It’s been an interesting few days on Twitter observing the machinations of so called ‘supporters’ of the maverick US Cancer cure Physician, Stanislav Bursynski. You may recall that this is controversial Doctor who uses film crews and patient testimonials as major platforms in his promotion of his clinic and specifically his ‘wonder drugs’ in for form of ANP’s. Other Clinicians use the time honoured tradition of arranging comparative and reproducible experiments which, when conducted and monitored properly, allow close scrutiny and debate over any new or improvement of a treatment. There are plenty of pieces in ‘blogland’ on the suspicion with which his clinical development strategy is held but it is ‘supporters’ who seem to be the ones fronting the major defence of his efforts to ‘cure’ peoples cancer. A number of them probably think they serve the Bursynski Clinic well in its efforts to encourage more desperately sad and broken spirits to weigh over a lifetime’s savings fund to this clinic. With little evidence to show prospective ‘new’ patients other than carefully constructed websites and choreographed films, the clinic needs all the ‘foot soldiers’ it can get to advance the case for its existence. One might be excused for thinking these Bursynski advocates had some technical knowledge of the subject that they appear, on the surface, to know so much about and talk with such authority on. Here are a few examples of the science based medicine approaches they take to convince ‘new’ patients to consider this approach and how they engage with Health care Professionals who spend most of their working lives truly caring for cancer sufferers.
This is the level of science application behind the so called 'fans' of Bursynski. The concern is that if these people play even a fraction of a role in persuading patients to go to this clinic then it’s a scary thought. When pro Bursynski supporters get all out of shape in interactions with oncologists and other health care professionals, it is most likely because they cannot access the basic tenets being debated – we shouldn’t underestimate their lack of understanding because they are clearly influencing those with difficult and sensitive choices to make for themselves and their loved ones. This is one of Bursynski’s legacies in not publishing acceptable protocols and then carefully monitored and scrutinised trials. The confusion caused amongst well-meaning but misguided people leaves them in a vulnerable position.
This reports the aim of a group of Australian Scientists to remove formal
University classes containing Alternative Medicine from the curriculum. It cites
the UK as another country which has made a similar move. Friends of Science in
Medicine (FSM) already has 450 members. They include Ian Frazer, the inventor
of the cervical cancer vaccine, and Sir Gustav Nossal, a renowned immunologist.
Among their group, 50 are international and they too hope to snuff out what they
refer to as modern-day quackery.