Surviving "Terminal" Cancer - Clinical trials, drug cocktails & other treatments your oncologist won't tell you about. Ben Williams, Ph.D. Fairview Press, Minneapolis, USA. August 2002. ISBN 1-57749-116-5. $21.95 (US). Can be ordered on-line from www.fairviewpress.org at an introductory discount of 20% until 31 December 2002.

Ben Williams is a man engaged in a quest, a quest to find the best available treatments for the glioblastoma multiforme tumour which invaded his brain in 1995. He is one of the very few long-term survivors of this highly malignant type of brain tumour whose victims typically have a prognosis of 10-17 months.

The title of his 275 page book is provocative and while it might attract the attention of patients and carers, it will probably earn him no marks among the oncologists, neurologists and neurosurgeons, who treat patients with brain tumours. This would be a great pity because Ben Williams has marshalled his formidable intellectual ability and research skills to provide valuable insights about the world of cancer treatment from the viewpoint of a patient.

The author is a man possessed - possessed with a persistence and a determination very often lacking in academic researchers. He has an obsession, albeit a 'gentle obsession', to identify the most promising treatments for brain tumour and cancer patients, not just in the USA, but anywhere in the world, in the UK, Japan or India, in any location where the latest trials are occurring. He has contacted researchers direct and spoken their own language, to prise the details from the fine print of their published clinical trials.

There is always a temptation, when you are driven by what others might regard as an obsession, to cut corners and to lose your research balance. Ben Williams has avoided these traps, his research is exhaustive and he is a man with a mission but his language is not polemic. There are 190 end-notes in the book, either giving full citations for his reference materials, or expanding on a point made in the text. He is critical of the US Federal Drug Authority (FDA) and its role in clinical trials for new cancer treatments but he has avoided promoting any conspiracy theories, which is often the pitfall of the amateur researcher. Who could blame him for having a mission? His very life and continuing existence has been challenged by this unwelcome visitor.

Professional psychologist

The author of this book is an amateur researcher in the world of oncology and clinical trials but has been a professional researcher in his chosen field of psychology and was Professor of Psychology at the University of California - San Diego when he was diagnosed in 1995 with a brain tumour the size of an orange and given eighteen months to live. Compared to most of us - patients, parents, spouses and carers - he had several advantages: a professional understanding of scientific methodology, access to research resources, and friends in the medical profession who were prepared to help him. As Ben explains, there were other circumstances: both he and his wife Diane were Professors, they had no children, and were financially secure.

Even before his book appeared Ben was well known in brain tumour circles. He was a participant on the US-based BRAINTMR e-mail discussion list, which brings together over 700 patients and carers, and several medicos, to discuss brain tumours. He is also the author of the resource available at Al Musella's Virtualtrials website "Treatment Options for Glioblastomas and Other Gliomas". As a long-term survivor he has received hundreds of inquiries from fellow patients, anxious to know what options he has tried.

I must say that I have spent several hours, since receiving my copy of Ben Williams' book, asking myself what I should do with it - should I publicise it and make it widely available to Australian patients and carers, or should I just let people find out about it through their own endeavours as many have done with an earlier book by another long-term brain tumour survivor "That's Unacceptable" (1997) by Rebecca L Libutti? Will it upset people in the throes of treatment or even those whose loved one experienced a brain tumour and subsequently died?

Questions

They may sound like pedantic questions from an over-scrupulous mind but to me they are real.

Soon after my late wife Marg was diagnosed with a glioblastoma multiforme brain tumour in 2000 I searched for information and one of the first resources I came across was the on-line book "Beyond the Road's End", written by Mary Catherine Fish about the very short five-month brain tumour journey of her husband Tom. Initially I thought I might read it aloud to my wife but as the chapters progressed the story became just too harrowing to even read silently to myself. I had to put it aside and come back to it, several times, and I am glad I did because it prepared me for what might come.

By the time of the neurosurgeon's post-operative visit to discuss the results of the pathology and confirmation of a glioblastoma, both Marg and I had learnt sufficient from that book and other on-line research to understand what he meant when he started talking about "an aggressive tumour", "dying from within", "necrosis" and so on. To some extent Marg was prepared when he explained that her prognosis was "months rather than years". (Transcript is available here.)

Since that time I have come across several brain tumour patients and their carers and I have been amazed to learn for myself something which is probably well known to doctors and nurses who deal regularly with cancer patients or those with a life-threatening disease - that not everyone is interested in learning about their condition.

Occasionally people will phone me and say they know of a friend whose wife or husband has been diagnosed with a brain tumour and is it okay to give them my phone number as someone who would be prepared to speak with them, if they wished.

I now tell people making these preliminary enquiries that I am quite willing, indeed, very willing, to speak with their friend but I warn them that more often than not no one will phone me.

The reason is twofold - for some, the only way they can deal with the diagnosis is to adopt an attitude of "denial"; for others, they retreat into the family, close ranks, and deal with it as a small, tightly knit group.

On the other hand, there is a steady stream of people who contact me and say that they obtained great comfort and knowledge from reading the web-diary of my wife's twelve-month journey with her glioblastoma and are grateful for the dozens of links I have provided to other on-line resources about brain tumours. They say that it was reassuring to know that others had been faced with the some issues that had upturned their life. Ben Williams believes that observing the journeys of fellow sufferers provides solace and insight.

Regret?

The other cause for hesitancy about publicising Ben Williams' book was that its reading may engender a feeling of regret and misgiving on the part of some whose loved one has already passed on. "Should I have done more?" "Should I have quizzed my oncologist about those experimental trials which are now generating good clinical trial results?"

It is all a question of balance, if a surviving spouse is going to have regrets then they can take many forms: "Did I make the best of the time that was left to us?" "Did I say everything I intended to say?" Even if knowledge about Ben Williams' quest engenders regret in some people, it could also encourage others to adopt a more pro-active involvement.

There has been another cause of hesitancy - will Ben Williams' unusual, maverick, and unilateral actions encourage others to follow suit, even though their capacity to do so in Australia might be more constrained?

Ben Williams' book is divided into three sections - his experiences as a patient (90 pages), observations of how the (US) medical system operates (44 pages), and information from outside mainstream medical practice (90 pages).

Ben was diagnosed after exhibiting mildly erratic behaviour - unsteady driving and parking at an angle, uncontrollable running, backaches, tiredness, and neglect of items in the left visual field.

A preliminary examination of his tumour sample taken during surgery indicated an anaplastic astrocytoma grade III and he therefore assumed his life expectancy might be 3 to 4 years but this was dashed a week later when the classification was changed to a glioblastoma multiforme grade IV and his neuro-oncologist spoke of eighteen months "because I appeared to be functioning at a high level".

BNCT

The first treatment protocol he considered was boron neutron captive therapy (BNCT) but he declined participation in a clinical trial when he discovered it would involve further surgery to obtain a tumour sample. He then considered a trial involving monoclonal antibodies but first commenced radiation therapy.

He spent each day during radiation therapy researching either PubMed or articles in the university medical library. He once returned to his office and wept harder than ever before in his life. Virtually every research paper had told him "how truly awful my prognosis was".

Following a bad reaction to the anti-convulsant medication Dilantin he was transferred to Tegretol but later unilaterally discontinued it.

At one of his early medical appointments he quizzed his doctor about research he had read about - Dr Burzynski's work with antineoplastons (see critical comments later in this review), Poly-ICLC, and tamoxifen.

His neuro-oncologist rejected Ben's suggestion of combining radiation therapy with tamoxifen but later agreed to its introduction after radiation had been completed.

He next considered brachytherapy but in the meantime, following extensive research, decided to supplement his prescribed dose of tamoxifen by purchasing additional supplies in Tijuana, Mexico.

Ben commenced BCNU chemotherapy and, again unilaterally, incorporated verapamil and accutane and, later, melatonin and polysaccharide krestin. His Doctor had substituted PCV for the the BCNU but later this was reversed.

Ben had a succession of good MRI results, culminating in June 1996 with no sign of residual tumour. He was convinced that the "cocktail approach" was working.

Self-treatment

I know that the honest reporting of his self-treatment will mitigate against some Doctors recommending this book to their patients. His comments about the dangers of self-treatment are confined to the small print of end-note 6 of chapter 7, rather than appearing in the main text; nevertheless, it is on record. He writes:

"Self-prescription can be risky in terms of potential side effects and drug interactions. But because Accutane (one of the drugs he added himself) was already used for other purposes I found a great deal of information about its potential toxicities and contraindications in the Physicians Desk Reference (PDR), the well-known pharmaceutical reference used by physicians. I determined that the threat posed by my glioblastoma loomed larger than the risks from the drug itself.

"Cancer patients are well advised to tell their oncologists about all the medications they are using. Adverse drug interactions frequently occur with prescription drugs and various supplements. Moreover, drugs often have potential side effects that need monitoring. For example, Accutane does have occasional liver toxicity, so liver enzyme tests are needed to ensure that such toxicity is minimised. Unfortunately cancer patients are often afraid to provide complete information to their oncologists because of the opposition they frequently encounter."

There is an interesting comment about meeting his friends at the International Congress of Psychology:

"My friends did not know how to relate to me; I appeared healthy enough, but they had been told I would likely die in the near future. People in general are uncomfortable when talking with cancer patients, because there is such a thin line between support and pity. I found that the best way to put people at ease was to talk about the situation as dispassionately as possible. A little humour went a long way too."

The lead up to and wait after MRIs generated great anticipatory anxiety for him. He is not alone, on the BRAINTMR discussion list carers, mostly women, refer to the two forms of "PMS". Ben had now taken tamoxifen for two years and wondered if he should discontinue it but as a precaution decided to continue it for another twelve months. Meanwhile, his neuro-oncologist moved to another practice but Williams continued with his own research, reading the latest reports in the medical literature and speaking to the researchers.

Diagnosis

Williams makes an interesting observation about the delivery and effect of a patient's diagnosis:

"Patients are entitled to an honest appraisal of their situation, but a positive outlook, even if unrealistic, offers at least a period of time where the patient is not overwhelmed by the depressing reality of his or her disease. On the other hand, false hope will soon be dashed, perhaps resulting in even greater despair."

He comments: "Simply making an effort to cope with a situation, even if I was unsuccessful, was therapeutic."

As he graduated to a two-year survival mark he received many enquiries but only a few either acted on his advice to be more pro-active, or succeeded in persuading their doctors to adopt the "cocktail approach". 200 patients or carers from around the world communicated with him, including some from Australia because through the Internet we have all been brought closer, particularly those who are interested in what is a less common disease.

EBM

In the second section of his book Williams is highly critical of the current medical system and the way in which practitioners routinely oppose 'unproven treatments'. I believe this attitude of scepticism stems from an overpowering emphasis on Evidence Based Medicine (EBM) but Williams does not explore this avenue. What is EBM?

"Evidence based medicine is the conscientious, explicit, and judicious use of current best evidence in making decisions about the care of individual patients. The practice of evidence based medicine means integrating individual clinical expertise with the best available external clinical evidence from systematic research." (Sackett DL, Rosenberg WMC, Gray JAM, Haynes RB, Richardson WS. Evidence based medicine: what it is and what it isn't. BMJ 1996; 312: 71-2)

The EBM approach permeates today's medical training. In the "Ideal Oncology Curriculum for Medical Schools" (intended for Australian medical schools) the first point in Objective 3.3 concerning Information Management is: "Describe the importance of evidence based medical practice" and a suggested typical question for students is: "Clinical freedom is the last refuge of the scoundrel" – discuss.

Have we embraced EBM so enthusiastically that it limits the opportunities available to cancer patients to be treated with and have access to promising but unproven treatments? It seems almost as if there is a necessary mantra that has to be recited before acceptance is granted and hence, one of Australia's major cancer organisations declares in an explanatory statement about its activities that it "... is committed to improving the prevention, detection and treatment of cancer by providing the best evidence-based information to cancer patients, doctors and health professionals and the general community."

Would any harm arise from including Ben Williams' book as required reading in an "ideal oncology curriculum"?

Williams is highly critical of the US Food and Drug Administration (FDA) and its reliance on the completion of successful Phase III trials before providing its official sanction.

The relevance of this to Australia is that the status of a new treatment under the FDA umbrella could conceivably influence what the Therapeutic Goods Administration (TGA) decides about that drug's use here.

Statistical significance

Using his academic and practical knowledge of scientific methodology he levels his sights against the FDA's adoption of .05 as an arbitrary level of "statistical significance". One chapter in this section of the book is entitled "Bastille Day for Cancer Patients" and it is a virtual call to action to revise the current method of approval of new treatments but no decapitations are proposed.

The third section of his book "What Your Oncologist Won't tell You" is the area likely to have an appeal to the wider audience of those grappling with a cancer, as opposed to a primary brain tumour. He does advise his readers to tell their doctor before using any new treatment.

I have a feeling that Williams' book will 'filter' gradually into the arena of popular cancer literature and that in years to come doctors are likely to be asked for their reaction to a whole raft of ideas which have their origin in his book.

Supplements

Here is a list of several of those topics and my rather shorthand description of Williams' comments about various supplements and complementary treatments: laetrile (no evidence of beneficial effect); hydrazine sulphate (no evidence); iscador (worth studying); ukrain (worth studying); melatonin (clear evidence of efficacy); PSK, lentinan and other polysaccharides (ambiguous); gamma-linolenic acid (GLA) (may have other beneficial properties); genistein (should be studied further); selenium (laboratory research has been promising); green tea (no apparent downside); limonene (early results promising); quercetin (perhaps); whey protein (promising); broccoli sprouts (laboratory research promising).

In his discussion of the role of supplements Williams has great admiration for the work of the Life Extension Foundation in Florida, just as I am aware that some Australian patients have made use of the advice of nutritionist Dr Jeanne Wallace in Utah.

Williams devotes several pages to a discussion of Dr Stanislaw Burzynski's antineoplaston treatment and his battle with US regulatory authorities. I wonder if he may have allowed his attitude towards the FDA to prompt a too open-minded evaluation, a bit like "the enemy of my enemy is my friend"? He says that "only time will tell whether the treatment will be effective". I have a more jaundiced view of the Burzynski approach, which is often publicised by unsuspecting journalists in the popular media, when a fund-raising appeal is launched to send someone for treatment in Texas. I have observed the stridency and argumentive vehemence of some of his Australian supporters and know of the expenditure of $50,000 on the treatment by one acquaintance without any apparent advantage.

The future

In the final chapters of his book Williams discusses research areas where success is likely to come - antiangiogenesis, inhibition of cell signalling channels, monclonal antibodies, gene therapy, and immunological treatments. He has a gifted capacity to translate difficult medical concepts into layperson's language. Here is his colourful analogy for the role of angiostatin and endostatin in preventing endothelial cells from replicating: "Like Napoleon's army in Russia, the ferocity of the cancer cell is irrelevant if there is no energy to sustain its advances".

I trust that this review has been sufficient to convey accurately what Ben Williams is about. For the time being, glioblastoma brain tumours remain fairly relentless but there are long-term survivors out there and this is the story of one survivor's journey. His story might contain the germ of an idea which will help others to join him.

Denis Strangman, Canberra, Australia

19 August 2002