Tuesday, 24 February 2015

Clarithromycin - a repurposed anticancer drug?

An antibiotic may join the ranks of drugs suitable for repurposing as anti-cancer treatments, according to new research from the Repurposing Drugs in Oncology (ReDO) project published in ecancermedicalscience.

Clarithromycin is a very common and effective antibiotic. It is traditionally used for many types of bacterial infections, treatment of Lyme disease and eradication of gastric infection with Helicobacter pylori. It is noted in the World Health Organisation’s list of essential medicines, ensuring it will remain available worldwide at low cost. Dr. Vikas P. Sukhatme of the ReDO project and GlobalCures says "The multiple mechanisms of action of this drug make it particularly attractive for repurposing."

“Clarithromycin is a canonical example of a drug that may have limited antitumor activity on its own, but is extremely valuable against cancer in combination with other drugs,“ says An Van Nuffel, PhD, lead author of the paper and member of the ReDo project and the Anticancer Fund.

An international collaboration between anticancer researchers from across the world, the ReDO project is dedicated to promoting the cause of common medicines which may represent an untapped source of novel therapies for cancer.

In partnership with ecancer, the ReDO project is publishing a series of papers on drugs with enough evidence to be taken to clinical trials. Future papers will address the potential anti-cancer uses of nitroglycerin, itraconazole and diclofenac.

Dr Gauthier Bouche of the ReDO project and the Anticancer Fund describes a serendipitous use of clarithromycin for the treatment of chronic myeloid leukaemia (CML).

In 2012, Italian doctors led by Dr Carella prescribed clarithromycin for an infection in a patient with CML. The patient had developed resistance to his treatment, which reversed after treatment with clarithromycin, reinstalled when the drug was discontinued and then reversed again after re-challenge.

Low- and middle-income countries (LMIC) may pave the way for drug repurposing. The latest randomised trial done with clarithromycin was done in Egypt, demonstrating that patients with a certain form of lymphoma lived longer when clarithromycin was added to chemotherapy.

The faster development of new - but expensive - drugs in High Income Countries may create a role for LMIC to further develop drug repurposing in oncology. Could LMIC with no access to the recent drugs perform trials with clarithromycin?

“If clarithromycin were a new drug with the anticancer potential that it has, we would see companies pushing hard for clinical trials and aiming to get to market quickly,” says Pan Pantziarka, PhD, member of the ReDO project and the Anticancer Fund. “Why isn't that happening now in multiple myeloma or resistant leukaemias?”

Thursday, 19 February 2015

Book Review - A Scientist in Wonderland

Keywords: Homeopathy, memoir, medicine
Title:A Scientist in Wonderland
Author: Edzard Ernst
Publisher: Imprint Academic
ISBN: 978-1845407773
Edzard Ernst initially came to prominence in the UK as Professor of Complementary Medicine, holding the first such chair anywhere in the world. That was in 1993, and Ernst, who already had a pedigree both as a clinician and a researcher, expected that his quest to rigorously apply the scientific method to the various fields of ‘complementary and alternative’ medicine would be welcomed by practitioners and adherents who would want to prove the efficacy of their different ‘modalities’. Now fast forward to 2015 and Ernst is in the public eye once more in the UK with the publication of ‘A Scientist in Wonderland’, his memoir that tells the story not just of his research findings, but also lays bare the meddling of Prince Charles, heir to the British throne and arch-proponent of homeopathy, detoxification theories and a raft of other ‘alternative therapies’.

The book describes Ernst’s circuitous route to that Professorship – from his unconventional upbringing in post-War Germany, his love of jazz and his hesitant move into medicine. This is an environment in which homeopathy and naturopathy are accepted to a greater extent than in the UK. Indeed his first posting is in Germany’s only homeopathic hospital, where patients seemed to respond well to the endlessly diluted concoctions which are homeopathic medicines. As he points out in graphic detail, there can be not a single molecule of active ingredient left in these medicines, but yet patients recovered. Evidence of effect? Or evidence of the natural evolution of many illnesses and the positive power of the placebo effect?

In time Ernst moves to more conventional medical institutions. In addition to growing clinical experience he also begins a research career, finding the role of scientist enormously rewarding and intellectually satisfying. His observes, wryly that:

An uncritical scientist is a contradiction in terms: if you meet one, chances are that you have encountered a charlatan. By contrast, a critical clinician is a true rarity, in my experience. If you meet one, chances are that you have found a good and responsible doctor. 

There are certainly plenty of patients who will echo that, and indeed it is a complaint that many cancer patients will recognise. Indeed, many of us hope that the Medical Innovation Bill (aka the Saatchi Bill, which Ernst does not support), will encourage more of this critical and scientific thinking in our doctors.

Wednesday, 4 February 2015

GcMAF Factory Raided

News from the UK's medical regulator, the MHRA, following a raid on the Cambridgeshire lab which was manufacturing GcMAF. This is a blood product that is sold over the internet as a cure for cancer, autism and a host of other conditions. While there is one bona fide early trial on GcMAF on-going in Israel, the product is being sold from a variety of websites as an actual cure. There is no evidence that it is a cure - and the Anticancer Fund of Belgium has been working hard examining the evidence that exists. To date a number of the papers that the people selling GcMAF have been using as 'evidence' have been retracted (withdrawn from the journals in which they were published). There is a good summary of the evidence at the Anticancer Fund website.

In this latest news from the MHRA, concern was raised about the safety of the product:

The blood plasma starting material being used to make this drug stated “Not to be administered to humans or used in any drug products”. It was concluded that the production site does not meet Good Manufacturing Practice (GMP) standards and there are concerns over the sterility of the medicine being produced and the equipment being used. There are concerns that the product may be contaminated.

The conclusion from the MHRA is stark:

These products may pose a significant risk to people’s health. Not only were the manufacturing conditions unacceptable but the originating material was not suitable for human use. GcMAF products labelled as ‘First Immune’ are not licensed medicines and have not been tested for quality, safety or effectiveness. People should not start treatment with these specific products. It is important that patients currently taking these products seek their doctor’s advice as soon as possible. People should continue taking prescribed medicines and follow the advice of their doctor.

Update: The BBC have reported that the government of Guernsey, where many of the companies selling GcMAF are based, has banned the importation of GcMAF. 

Monday, 2 February 2015

Open Letter - Medical Innovation Bill

Today's Daily Telegraph includes an open letter in support of the Medical Innovation Bill (aka the Saatchi Bill). The letter was conceived and organised independently of the official Saatchi campaign. The letter, which carried 52 signatures, was edited for publication. The full text is reproduced below:

------------------------------------------------------------
The Letters Editor
Daily Telegraph
London
29/01/15

Dear Editor,

We note with considerable interest the successful third reading of the proposed Medical Innovation Bill, aka the Saatchi Bill. While there have been significant advances in cancer treatments in recent decades there remain areas where there has been no meaningful advance. Diseases such as glioblastoma, sarcoma, pancreatic cancer and others have seen no clinically relevant improvements over those same decades. Refractory metastatic solid tumours remain a challenge and a significant cause of morbidity and mortality. Furthermore, for many less common diseases the landscape of clinical trials is barren.

While it is true that clinicians have lee-way to prescribe drugs ‘off-label’, we know from our direct experience with patients that viable clinical options are not being accessed in the vast majority of ‘terminal’ cases. When all standard therapies have failed, and there are no clinical trials available for the patient, the response is almost uniformly to move that patient into palliative care. Too often it appears that clinicians are reluctant to try treatment alternatives – be they metronomic chemotherapies, repurposed non-cancer drugs with evidence of efficacy or compassionate use/medical needs programs. Note that these are all options with often considerable levels of clinical and pre-clinical evidence; this is not junk science or quackery.

We do not dispute that the clinical trial is necessary in order to identify those advances that work and those that do not. However, the evidence base for medicine can come from many different sources. Data collection is a necessary corollary of increased off-label usage and the new registry included in the Bill will record information (including side-effects and outcome data), in every instance of an innovative treatment under the terms of the Bill. This ground-breaking registry will enable us to mine and analyse real world data so that we are not dealing with a set of anecdotes, but validated and clinically useful information and so providing greater patient protection than exists at present. Physicians treating patients with no other options would be empowered to evaluate off-label interventions with the highest evidence of efficacy.

The reluctance of physicians to explore alternative options may not be solely due to a fear of litigation, as Lord Saatchi contends. There are other social, cultural and institutional barriers at work – individual and institutional comfort zones – which often preclude off-label prescribing. However, if the passing of the Bill affects a change in thinking such that there is a greater willingness to explore potentially helpful treatments, then it will have provided benefit to patients. Passing the Bill sends a positive message that encourages responsible use of off-label options. Not passing the Bill sends a strong negative signal that off-label usage is neither encouraged nor supported.

Ultimately the question that must be addressed is: what can we responsibly offer to those patients for whom there are no suitable clinical trials?

Yours Sincerely,
  • Pan Pantziarka PhD, The George Pantziarka TP53 Trust, London (UK) & Anticancer Fund, Brussels (Belgium)
  • Dominic Hill - www.survivingterminalcancer.com Film maker & patient advocate (UK)
  • Professor Marc-Eric Halatsch, Oncological Neurosurgeon and Professor of Neurosurgery, University of Ulm (Germany)
  • Lydie Meheus PhD, Managing Director, Anticancer Fund, Brussels (Belgium)
  • Dr. Gauthier Bouche, Medical Director, Anticancer Fund, Brussels (Belgium)
  • Richard Gerber, PhD, long-term glioblastoma survivor and patient advocate (Italy)
  • Professor Angus Dalgleish, St George's Hospital, University of London (UK)
  • Professor Ahmed Ashour Ahmed, Professor of Gynaecological Oncology, University of Oxford, Consultant Gynaecological Oncology Surgeon (UK)
  • James Hargrave, Empower Access to Medicine (UK)
  • Dr John Symons, Director, Cancer of Unknown Primary Foundation (UK)
  • Fl√≥ra Raffai, Findacure (UK)
  • Professor Stephen Kennedy, Professor of Reproductive Medicine, University of Oxford (UK)
  • Dr Ian N Hampson, Reader in Viral Oncology, University of Manchester (UK)
  • Professor Andy Hall, Associate Dean of Translational Research, Newcastle University (UK)
  • Professor Emeritus Ben A. Williams, Psychology, long-term glioblastoma survivor, patient advocate, Moore’s Cancer Center, University of California, San Diego (USA)
  • Dr Al Musella, President, Musella Foundation, founder The Grey Ribbon crusade: umbrella organisation for over 100 brain cancer charities (USA)
  • Professor John Boockvar, Director, Brain Tumor Center Lenox Hill Hospital NYC, Professor of Neurosurgery (USA)
  • Professor Emil J Freireich, Ruth Harriet Ainsworth Chair, Developmental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas (USA)
  • Brett Shockley - patient advocate (USA)
  • Professor David Walker, Professor Pediatric Oncology, University of Nottingham (UK)
  • Laura Mancini, PhD, Clinical Scientist, National Hospital for Neurology and Neurosurgery, UCLH NHS Foundation Trust, London (UK)
  • John Morrissey, Adviser to the Childrens Cancer Research Fund (USA)
  • Stephen Western, patient advocate, Astrocytomaoptions.com (Canada)
  • Richard E. Kast, MD, IIAIGC Study Center (USA)
  • Charlie Chan DPhil FRCS, Consultant Breast Surgeon (UK)
  • Professor Chas Bountra, Professor of Translational Medicine, University of Oxford (UK)
  • Dr Henrietta Morton-King, North Cumbria University Hospitals Trust (UK)
  • Dr Andrew Brunskill, Clinical Assistant Professor of Epidemiology and Health Services, University of Washington Seattle (USA)
  • Vincent Galbiati, President & CEO of Tomorrow’s Cures Today, Washington DC (USA)
  • Neil Hutchison, Founder - Magic Water Pediatric Cancer Foundation - San Diego (USA)
  • Fiona Court, Consultant Oncoplastic Breast Surgeon, Cheltenham (UK)
  • Professor Alastair Buchan, Head of the Medical Science Division and the Dean of the Medical School at the University of Oxford (UK)
  • Dr. Georgios Evangelopoulos, patient advocate, lawyer & political scientist (Greece)
  • Professor John Yarnold, Professor of Clinical Oncology at The Royal Marsden and Institute of Cancer Research (UK)
  • Professor Jerome H Pereira, Consultant General & Oncoplastic Breast Surgeon, Norwich Medical School University of East Anglia (UK)
  • Dr Lynne Hampson, Non Clinical Lecturer in Oncology, Institute of Cancer Sciences, Manchester (UK)
  • Professor Robert Kirby, MD, FRCS, Consultant Surgeon and UHNM Hospital Dean (UK)
  • Professor Gareth Evans, Professor of Medical Genetics and Cancer Epidemiology, University of Manchester (UK)
  • Dr Rupert McShane, Coordinating Editor Cochrane Dementia and Cognitive Improvement Group, Oxford University (UK)
  • Michael Shackcloth, Consultant Thoracic Surgeon, Liverpool Heart and Chest Hospital (UK)
  • Professor Vikas P. Sukhatme, Professor of Medicine, Harvard Medical School, Co-founder Global Cures (USA)
  • Vidula Sukhatme, Co-founder Global Cures (USA)
  • Sarah Lindsell – CEO, The Brain Tumour Charity (UK)
  • Neil Dickson - Chairman, The Brain Tumour Charity (UK)
  • Alex Smith (Founder, Harrison’s Fund) (UK)
  • Giles Cunnick, Consultant General & Breast Surgeon, Bucks Healthcare NHS Trust, (UK)
  • Dr Piers Mahon, Biotech Consultant, (UK)
  • Paul Fitzpatrick, Chairman, Duchenne Now, (UK)
  • Dr David Faurrugia, Consultant Oncologist, Cheltenham General Hospital (UK)
  • Dr Chris Govender, Medical Officer in Addictions, (UK)
  • Sue Farrington Smith, Chief Executive, Brain Tumour Research, (UK)
  • Professor Steven Gill, Professor in Neurosurgery, University of Bristol (UK)


Wednesday, 21 January 2015

Live Blood Analysis - A Scam

Dr Henry Mannings, who went through hell with the General Medical Council last year after facing groundless accusations from a vindictive consultant oncologist who objected to what the Star Throwers charity was telling his patients, recently sent me a price list from a well-known private clinic that specialises in treating cancer patients. What was shocking to us was not just the prices charged but that this clinic offered patients a service called 'live blood analysis'. Like Dr Mannings I am astounded that any reputable doctor would be offering this to patients, but it is offered and it's not cheap. So, for those who might be interested, just what is 'live blood analysis' (LBA) and is there any evidence that it is useful?

LBA, (which is sometimes called Hemaview, live cell analysis or nutritional blood analysis) is a procedure that involves taking a sample of blood, putting it on a slide and taking a look at it using a microscope. From this it is claimed that a skilled LBA practitioner can detect cancer, immune disorders, yeast and bacterial infections and a spread of other conditions. Patients will be told that the cells are not moving about in the correct way, or that they look abnormal or are showing signs of fermentation or infection and so on. Patients will be told that conventional blood tests cannot capture many of these issues because they do not look at live cells in motion. A lot of scientific sounding terminology will be used along the way, and of course the microscope is a scientific instrument so all of this must be based on fact, right? Wrong.

There is no scientific evidence for LBA. It is junk science - something dressed up to look like science but not based on any evidence or credible scientific theory.

Tuesday, 13 January 2015

Book Review - 'Being Mortal' by Atul Gawande

Keywords: Cancer, aging, medicine
Title:Being Mortal: Illness, Medicine and What Matters in the End
Author: Atul Gawande
Publisher: Profile Books
ISBN: 978-1846685811

In 'Being Mortal' Atul Gawande asks a series of difficult, important but uncomfortable questions about the nature of medicine and mortality. These are tricky waters to navigate, but essential all the same as it gets to the heart of what it is we want medicine to do for us. But navigate them we must, both because we have an aging population that often faces impossible choices regarding social care and also in the context of increasing cancer incidence (one of the consequences of that aging).

The author, a practicing doctor, uses the experiences of family, friends and patients alike to illustrate the choices that face us both in aging and in cancer care. He skilfully weaves in these experiences and in doing so puts complex problems into real situations so that he explore the options available, the things we want and cannot have and also, just importantly, draws out the underlying questions. He explores the history and evolution of patient care, how changes in the pattern of work and family life have impacted our expectations of old age. The contrasts between what we want in terms of autonomy and quality of life on the one hand, and what our medical and social care systems provides on the other are brought sharply into life. For those of us who have had to navigate these problems for elderly relatives it is familiar territory outlined with a thought-provoking honesty.

In terms of cancer the problems are starker still. When treatments fail what do we want to do? We are up against the limits of what medicine can deliver. Up against what our medical systems can cope with. The dilemma here is to risk cripplingly expensive new treatments, often with horrendous side effects or to opt instead for palliative or hospice care. These are hard choices to make, assuming we are given the choices in the first place. Sometimes there are less toxic options to try, but many doctors seem to prefer to go for the toxic chemotherapy route rather than step back and look at what the patient wants.

If there’s a theme that jumps out from this book it is that we need to be moving to a different model of the patient-doctor relationship. Dr Gawande describes this admirably. There is the doctor as expert doling out wisdom from on high. There is the doctor as information source giving facts and figures impartially to patients ill-equipped to come to a decision. And then there is the hardest option of all, which is the doctor as partner to the patient. A doctor who engages with the patient to discover what it is that is most important to them and then to help the patient make the choices that deliver the best compromises that are possible. Unfortunately many doctors are simply not trained or don’t have the tools to take this role, which is hard on the patients but hard too for the doctors.

While this is a challenging book at times, it is never sentimental or emotive, it’s humane and concerned. Medical systems the world over are in flux, struggling to cope with the increases in demand that our successes in medicine have delivered. In many ways we should not lose sight of how much progress we have made. But neither should we be happy with the status quo that leaves so many patients poorly served. Something has to give. And perhaps part of what has to give is that old-fashioned view of the doctor as expert, with the patient as passive receiver of care with no say in their own treatment.

Monday, 22 December 2014

When less is more

The conventional approach to chemotherapy treatment for cancer is to give the patient a cocktail of different chemo drugs at the maximum tolerated dose (MTD). The idea of MTD treatment is to hit the cancer with the most toxic treatment the patient can stand in the hope that it causes the maximum damage to the disease. Normally a treatment consists of a number of cycles of chemo using a mix of drugs, with the idea that each drug will attack the tumour in a different way – reducing the chance of the tumour surviving the onslaught. And it’s an onslaught for the person receiving the treatment too – most chemotherapy drugs are toxic to a wide range of cells, not just cancer cells. Hence the hair loss, the nausea, the immune suppression, fatigue and the rest of the side effects that makes chemo so hard.

Of necessity a person needs recovery time after each cycle of chemotherapy. Blood counts need to recover, sickness needs to pass, people need to regain some strength. Unfortunately that’s recovery time that tumours can also use to recover. The highest rates of tumour kill tend to be at the least cycles, the later cycles tend to be less effective, particularly if resistance starts to kick in.

However, this isn't the only way of delivering treatment. An alternative approach to chemotherapy has been developing for some time. Low dose metronomic chemotherapy involves many of the same drugs as MTD chemo, but delivered at low doses, often in tablet form, but with no treatment breaks. The continuous dosing is possible because at these low doses the drugs work in very different ways to when they are delivered at MTD levels. The side effects are minimal as the drugs are no longer acting as potent toxins to massively kill cells.