Background to the Treatment of Cancer with Promethazine (Phenergan)

Robert Jones MA PhD
The Promethazine or Phenergan® cancer treatment was developed by Robert Jones MA PhD as an effective and inexpensive means to kill cancer cells and increase survival rates.

This article is for interest only and should not form the basis of diagnosis or treatment of any medical condition or illness. If you are unwell or have a specific medical condition, please base your healthcare decisions on the advice of a medical doctor or other healthcare practitioner.


CANCER BEGAN to receive serious attention shortly after the war, when resources became available to study the problem. Despite the impressive acquisition of knowledge and major improvements in the treatment of several forms of the disease since then, the overall success rate remains dismally poor. The basic intention behind many of the putative solutions has been to impose a particular form of cell death upon the malignant cell, be it jamming of the blueprint for growth, inhibition of an enzyme essential to its metabolism, interference with a specific cellular function, or whatever. Remarkably, up to now nobody has even suggested that the consistent failure of these unquestionably clever schemes to produce an acceptable solution might perhaps indicate that the strategy is fundamentally flawed. Almost a century ago the German chemist Emil Fischer commented, 'If we wish to catch up with Nature, we shall need to use the same methods as she does.' It is the studied alignment with Fischer's guidance that sets the present approach apart and offers genuine hope for the future.

What follows is a brief account of the introduction of a cheap, safe, humane and largely successful means of treating malignant disease into the public domain and of some of the problems encountered on the way. As for myself, I graduated from Cambridge in 1954 after specialising in biochemistry, and entered cancer research five years later. Within a few weeks I had my first glimpse of the ravages the disease may cause. A rat had been fed with a liver carcinogen as part of a research program. The profusion of nodules of all sizes and colours in an organ usually accounting for 3% of the weight of the animal but which in this case was 25% was a sight never to be forgotten. Ten depressing and frustrating years were spent trying to get some kind of handle on the problem. Elsewhere I have written, "… for anyone presumptuous enough to attempt to solve it, the cancer problem has consistently presented a smooth and unassailable rock face." Although the accumulated experience was to come in useful later, no real progress was made. Accordingly I switched to working on toxicology, and then on heart transplants.

Five years later a huge stroke of luck brought me back to cancer again. A series of chance events led to the conclusions that (1) those agencies which injure cancers within the body of a host nearly all act indirectly, (2) all malignant cells possess a self-destructive mechanism which can be activated in a variety of ways, and (3) activation of the mechanism disrupts energy metabolism, leading to the death (necrosis) of the cancer cell. Oxygen and several enzymes participate in the functioning of the mechanism, which exploits a common metabolic weakness in the power houses (mitochondria) of malignant cells, distinguishing them from normal healthy cells. The absence or inhibition of any one of the necessary components enables the cell to evade death.

Late in 1975 I witnessed at first hand haemorrhagic necrosis inflicted by the bacterial derivative endotoxin on sarcomas grown beneath the skins of a group of mice. The venerable origins of the phenomenon lie in the distant past, when it was noticed that cancers occasionally regressed in response to host infections long before the role of bacteria in illness was discovered.


Deciduous tumours after endotoxin treatment of mouse hosts

In the animal experiments the tumours shrank, hardened, and fell off within a fortnight. The event was a watershed in the project. I happened then not to be aware of Fischer's insight, but instinctively I recognised that if the disruption of energy metabolism was an essential prelude to the development of necrosis, then this could be an important milestone in the battle against malignant disease.

At this point I had another stroke of luck. Within a few weeks I showed that the production of chemical energy within the tumour was totally disrupted within a few hours. My hunch had been right. The same changes did not occur in liver, even with several times the amount of endotoxin. Unfortunately the best endotoxin can do in man is to produce temporary regression, often with distressing and unacceptable side effects. The indirect nature of the action suggested that hormones acted as intermediary agents, from which the tentative conclusion that anti-cancer activity might be reproduced by pharmacological means was only a short step. The ultimate aim has been to obey Fischer's dictum to reproduce pharmacologically in man the same process by which endotoxin kills off animal tumours, albeit rather more slowly. There seemed to be a very good chance that selectivity of action would be preserved in therapies based on the same principle of cellular destruction. Because of the metabolic weakness of mitochondria, all forms of cancer are more vulnerable to attack than non-malignant tissues of the body, and are therefore expected to be sensitive.

These heretical concepts made no impact on the cancer establishment. In 1982 it became clear that the psychotropic drug chlorpromazine (Largactil), widely introduced for the treatment of schizophrenia almost thirty years earlier, could be used for the treatment of cancer. Several physicians who reported various degrees of success in treating cancer with chlorpromazine had been consistently ignored. It was shown as long ago as 1959 that this particular drug shares with endotoxin the ability to disrupt energy production in a mouse tumour. Its action, though nowhere nearly as dramatic as that of endotoxin, is clinically valuable. A detailed analysis of the evidence supporting the reports of the doctors, including anecdotal case histories, epidemiology, animal experimentation and mechanism of action, was published at the end of 1985 in the Italian journal Tumori (vol. 71: pp.563-69).

Clinical trials were at the time mostly conducted by two major cancer charities, the Cancer Research Campaign and the Imperial Cancer Research Fund. The two organisations recently merged to form Cancer Research UK. The analysis presented a strong case for the immediate adoption of chlorpromazine in cancer therapy, but in the following year the conclusions were rubbished by the Cancer Research Campaign in a letter wilfully based on misrepresentations of the information presented. A similar approach made at the same time to the Imperial Cancer Research Fund also foundered. A request to the Medical Research Council in Edinburgh to consider putting chlorpromazine into a clinical cancer trial was also ignored. Chlorpromazine is available in England only on prescription, and attempts to interest doctors in offering the drug to hopeless cases were unsuccessful.

At the end of 1990 Dr Riad Mahmud, an Egyptian diabetologist working in London, told me in a chance conversation that he had successfully treated three cases of inoperable pancreatic carcinoma with promethazine (Phenergan), a drug similar in chemical structure to chlorpromazine. Pancreatic cancer is one of the more serious forms of malignant disease. The condition is painful, and morphine is contra-indicated as an analgesic. The five-year survival rate is only 2-4%. Tragically my colleague had kept quiet about his extremely important findings made in Kuwait almost twenty years before. I encouraged him to publish, but it did not prove possible to retrieve his clinical notes from the Kuwaiti hospital where he worked before he died suddenly and unexpectedly in 1993.

I was familiar with promethazine as an excellent paediatric sedative which our family obtained on prescription and used in the 1970s. What I did not find out until 1994 was that some years earlier the drug became freely available over the counter in England. Towards the end of 1995 I drew up a self-medication protocol for cancer patients with promethazine as the active principle and posted it on four Internet noticeboards at the end of March 1996. I made no secret of my activities. In May a retired pathologist expressed an interest in my plans. At his request I sent him a copy. Late in June I received a warning letter from the Medicines Control Agency in London advising me that publication constituted advertising, and was therefore in breach of both European Union and United Kingdom law. This act of deliberate suppression placed a sharp curb on my activities.

In the summer of 1996 I marshalled the evidence in favour of conducting a clinical trial with promethazine in the form of a memorandum (Notes on the Treatment of Cancer with Low-Dose Phenothiazines, with Special Reference to Promethazine). Revised versions have been subsequently published in book form (in: Non-Antibiotics: a New Class of Unrecognised Antimicrobics, eds. AN Chakrabarty, J Molnar, SG Dastidar, N Motohashi, pp. 79-93. National Institute of Scientific Communication, New Delhi, India: I998) and on the Internet (currently www.cancersupportwa.org.au/Spotlight/index.htm). A copy was submitted to the Imperial Cancer Research Fund in September. Three months later, and after 40,000 more deaths from cancer in the United Kingdom, I was informed that the memorandum had been seen by a senior clinical oncologist. I was also told that the Fund was not working on the topic of phenothiazines and cancer; neither were there plans to do so in the future.

The Cancer Research Campaign was also contacted in the same year. A senior Campaign spokesman explained that major improvements in cancer treatment were expected to come from discoveries and advances in molecular biology. The cancer research industry confidently anticipates the answer to lie in gene therapy. For that reason there was no point in taking steps in the directions I suggested. Meanwhile attempts to interest patient support organisations in the London area led nowhere. Those few anti-cancer drugs introduced in the past decade or so have failed to produce any major advance in the general treatment of the illness.

The biggest shock over the entire duration of the project was finding how few patients wanted to be rid of their disease. In sharp contrast with expectations, the attitudes of nearly all the small group of individual sufferers to whom free advice was offered were dismissive. One patient who did take note, a lady in her forties with metastasising breast cancer, stopped treatment through no fault of her own after five months, which was much too soon. Through an administrative error there had been a delay of nine months in attending a London teaching hospital. So bad was the pain she was suffering from peripheral neuritis caused by radiotherapy that she wanted to return to the hospital to have her arm amputated. At the time of commencing the therapy she was not expected to survive more than a few months. During the five months of therapy both her neuritis and two out of four secondary deposits in the bone disappeared, the former for good. Although she enjoyed over a year of high-quality survival, she died eighteen months later. Everything was doomed to fail.

Meanwhile Don Benjamin, the active leader of the Cancer Information Support Service (CISS) in Sydney, Australia, picked the original publication up from the Internet. He condensed the advice down to a single page and published it in the newsletter of the CISS. Two patients failed to benefit; they had been taking high-dose vitamin E, contra-indicated for this form of treatment. The Cancer Support Association of Western Australia (CSA) had an arrangement with CISS whereby articles appearing in Sydney were reprinted in its own newsletter. A year later a farmer's wife in Western Australia was diagnosed with non-Hodgkin lymphoma. Jill Royce was no stranger to cancer, having survived melanoma some years previously. She felt shattered by the news. Wondering what best to do, she went to a public library nearby and asked the librarian if there was anything available which might help her. She was handed a sheaf of back-numbers of CSA newsletters. Jill found the advice Don Benjamin had condensed, together with the final key words I used in March 1996; what do you have to lose? Nothing, she decided.

After eight months Jill's oncologist told her that her tumour had disappeared. With innate courtesy she wanted to discover the identity of the person to whom she owed her survival. In 1998 she wrote me a letter of thanks. Most unfortunately the recommendation to continue with the medication for at least six months after the apparent disappearance of malignant disease, which Don Benjamin had been careful to include, had been overlooked, but everything seemed to be going well. It is impossible to overstress the importance of this crucial piece of advice. The oncologist had not been correct; Jill was not entirely free of cancer. Her tumour returned in the spring of 1999. After that she had a very difficult time, but at one point it did seem she was out of danger once more. Ever the optimist, she wrote a book about her experiences and had it printed privately (How We Controlled Our Cancers: Wesprint Holdings, Western Australia, 2001). At the end of 2001 it seemed probable that a form of cancer wholly resistant to therapy had emerged as a result of inactivation of the cell-destructive mechanism, possibly as a result of her exposure to the mutagenic agent chlorambucil. Now the cards were well and truly stacked against her. Very sadly Jill died in June 2002.

Jill's tragic experience brought a major problem into sharper focus. Conventional treatments for cancer may resort to any one of a number of approaches which, it is hoped, will prove effective. Two techniques in common use involve exposure to cytotoxic agents or to radiotherapy or both, creating environments supposedly lethal to malignant cells. One difficulty is that instead of procuring death the outcome may be cellular mutation with survival, resulting in the loss of a cellular constituent. If the missing component happens to be an enzyme involved in the necrotising mechanism, the cell will be unable to undergo necrosis. A clone of cells resistant to many forms of treatment may arise in consequence. Cancer is greatly feared for a number of reasons, not the least of which is that certain forms are known to be untreatable, while the survival rate in others is often unimpressive. Failure will not be the fault of promethazine. To put the matter into blunt context, orthodox treatments for the disease may already have put the patient at additional risk. Whether or not any doctor would be prepared to get the message accordingly and take appropriate action is debatable.

Before her disease became terminal, Jill persuaded several cancer patients to take her advice. In November 2002 it was heartening for me to meet four survivors whom she encouraged to try therapy with promethazine. One had non-Hodgkin lymphoma. Another had breast cancer with metastases in both lung and liver. A third had grade III astrocytoma, while the fourth was suffering from leukaemia. None was benefiting from conventional treatment at the time promethazine was started. All began to improve and at the time of writing are doing well. In 1997 I was able to help a lady in the north of England with carcinoma of the pancreas. She overcame her illness, and as recently as September 2002 was reported in a newspaper article to be successful in a new and important career. To my disappointment she has chosen not to speak of her experience and to deny ever having taken promethazine.

Since 1994 it had been my hope that a sufficient number of cancer patients would go along with the free advice and, with luck, might spread the word and generate publicity. Patient pressure, I thought, might persuade cancer charities or even individual doctors to conduct trials, or to offer the advice to individual patients. Most regrettably this has still to happen. The majority of cancer sufferers to whom the therapy has been offered has refused to proceed; none of them has survived. Friends convinced of the potential value of following the recommendations have encountered a similar scepticism. There appears to be no common reason for this behaviour. Some cancer sufferers wait until a point of no return is reached, when rescue is no longer possible. It might be added that those patient who have the courage to realize that for them the writing could be on the wall and who take immediate action are the ones who derive maximum benefit.

Another factor may be described as the white coat syndrome. Society accepts doctors as omniscient, all-powerful beings. In the mind of the man in the street, the original thinking and experience of a PhD counts for nothing beside the authority of the medical doctor. Most patients are amazingly loyal to their doctors, even though the treatments they may already have endured are often closer to medieval tortures than to twenty-first century medicine. Up to now I have been careful not to contradict advice from the medical profession, but the realisation that exposing tumours to a mutagenic environment from radiotherapy and cytotoxic drugs itself carries risk has altered the situation. Patients should not be afraid of asking what the effects of orthodox treatment are in both the short and the long term, and especially what the chances are of improvement or cure. The unhappy truth needs to be faced that when cancer is spreading through the body, the disease is almost always beyond the reach of conventional medicine. In contrast the good news is that secondary deposits produced from a primary growth should retain the same sensitivity to promethazine as the cancer from which they are derived.

Over the years opposition, sometimes intense, occasionally angry, and even subversive, to this new form of treatment has been encountered from every quarter. Efforts to encourage the main cancer charity in the United Kingdom, Cancer Research UK, to set up a pilot cancer trial centred on promethazine as the active agent continue to be ignored while its appeals for money keep dropping through the letter box.

It may be added that the introduction of promethazine dates back to 1947, from which the safety of the agent is immediately apparent. It also means that patent cover has long since lapsed world-wide. As a result promethazine is not expensive, although in 2002 the price of a 25mg tablet was raised from 3c to 31c in the United States. One pharmaceutical manufacturer explained that a clinical trial along the required lines would cost between one and two million pounds. Were such a trial to be successful, a number of companies could be expected to manufacture the active principle, and that any potential profit would be swallowed up by undercutting and perhaps by litigation as well. From this it is clear that cancer therapy with promethazine is too cheap to offer any financial incentive to drug firms to invest in development. In the United States another drug company declined to sign a confidentiality agreement, an essential preliminary for serious negotiations, unless the intellectual property to be presented was not only disclosed in advance, but the identities of all previous parties privy to the property were also revealed, together with exact descriptions of the information provided.

Not much experience was needed before it became clear that attempts to change attitudes and practices within the medical profession were most unlikely to succeed. Almost all doctors whom I have sought to interest in this form of cancer treatment have given an impression of extreme cynicism. Their responses vary in details. Some feel that a drug as harmless as a paediatric sedative and an anti-histamine just could not possess the power to defeat so widespread and well-entrenched disease as cancer. The line has also been taken that the ability of promethazine to cause tumours to regress should have been discovered decades ago, but because it was not, it cannot be genuine.

Actually, the reasons why the effect has been missed could not be predicted. First, discontinuity of treatment renders the drug ineffective. Second, anti-tumour action is slow, and emerges only with patience. And third, nobody has been looking out for an effect against cancer. Doctors have not realised that precisely the same blinkered scepticism they themselves now display characterised the reception of the separate discoveries by several physicians of the anti-cancer action of chlorpromazine years ago. The absolutely essential feature of maintaining continuity of medication has not been recognised, which bodes ill for the future of patients perhaps also unaware of the importance of keeping the therapy going months after the disappearance of malignancy.

Other doctors seem to be petrified of stepping out of line. In theory there are orthodox treatments for all forms of cancer. Recommending an untried therapy that clearly lies outside current practices, even though the unspoken truth is that a majority of conventional therapies fail to work, could lay a medical practitioner open to litigation. Serious career damage might follow. Here blame can be laid at the door of today's burgeoning culture of greedy litigation.

The responses of the scientific establishment have not been helpful. Although the technology for studying tumour destruction in experimental animals by disrupting energy metabolism selectively in malignant cells is simple and can be cheap, emphasis within the great majority of cancer research institutes is on molecular biology. Most of this work represents the achievement of genius; the trouble is that little of it is of immediate relevance to the situation of the cancer patient. Not many cancer research institutes are adequately equipped to study energy metabolism in tumours. Worse, the science of intermediary metabolism which holds the key to unlocking the cancer problem has become obsolete, and in recent years has been increasingly sidelined and omitted from the syllabuses of medical schools and departments of biochemistry. This was already a problem for me while I was still active in research up to the end of 1983, when the facilities I was able occasionally to use were available on an ad hoc basis.<

Nonetheless, as the Notes on the Treatment of Cancer with Low-Dose Phenothiazines… clearly show, the advice on offer lies fully in the mainstream of scientific enquiry linked to medical practice. Its shortcomings include the lack of firm information on a number of questions and an emphasis on theory. This in turn reflects my professional fortunes, which became irretrievably damaged at the end of 1983. The fact that I did not abandon the project then and there bears witness to the personal faith which the principles underlying the project have inspired.

As indicated above, the hope entertained for the future that pressure created by patients on doctors, cancer charities and medical authorities might lead to offering cancer sufferers a cheap, safe and humane alternative to orthodox treatments has proved feeble. Meanwhile rates of cure by conventional means remain obstinately and scandalously low. While the importance of figures for the success rate with the suggested protocol cannot be overestimated, no precise information can be given because feedback from patients and their relatives is seldom provided. The grossly unsatisfactory nature of the present situation, militating as it does against advances in the treatment of the disease, is openly acknowledged.

It may be argued too that the therapy takes too long to accomplish its purpose. The point is readily accepted. Access to laboratory facilities over the past twenty years would have improved matters. An analogy may be drawn with the achievement of powered flight by the Wright brothers. Such was the rapidity with which the technology progressed that once the discovery registered in the minds of governments and the public, within less than fifteen years technical advances had led to the use of aeroplanes, most regrettably, in warfare. The Concorde of faultless cancer treatment may still be years away, but, to extend the metaphor, progress may be regarded as having already reached the era of the SopwithPup. No harm will be done if cancer patients regard themselves as pioneers. For those for whom the treatment works, pleas are made on behalf of cancer patients in the future. Please place me in a better position to assist others by providing me with information about your case; please spread the word; please try and interest journalists and the media in your case; please agitate to get the therapy backed by administrators and politicians; and please urge the medical profession to consider the therapy seriously.

I no longer have a great deal of time. I have been battling against this cruel and merciless disease on behalf of cancer patients and their families for almost half a century; now see if you can be successful.