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Hyperthermia, Fever Therapy for Cancer – a viable alternative

16th April 2007 by Arrow Durfee Posted in Uncategorized

To read this article in full you will have to go to this site and register. It is free. pmj.bmj.com/cgi/content/full/79/938/672

Dr William Coley and tumour regression: a place in history or in the future

S A Hoption Cann1, J P van Netten2 and C van Netten1
1 Department of Health Care and Epidemiology, University of British Columbia, Vancouver, British Columbia, Canada
2 Special Development Laboratory, Royal Jubilee Hospital and Department of Biology, University of Victoria, Victoria, British Columbia, Canada

Correspondence to:
Dr S A Hoption Cann
Department of Health Care and Epidemiology, University of British Columbia, 5804 Fairview Avenue, Vancouver, BC, Canada V6T 1Z3; stephen.hoption.cann@ubc.ca

Submitted 15 July 2003
Accepted 20 August 2003

Spontaneous tumour regression has followed bacterial, fungal, viral, and protozoal infections. This phenomenon inspired the development of numerous rudimentary cancer immunotherapies, with a history spanning thousands of years. Coley took advantage of this natural phenomenon, developing a killed bacterial vaccine for cancer in the late 1800s. He observed that inducing a fever was crucial for tumour regression. Unfortunately, at the present time little credence is given to the febrile response in fighting infections—no less cancer.

Rapidly growing tumours contain large numbers of leucocytes. These cells play a part in both defence and repair; however, reparative functions can also support tumour growth. Intratumoural infections may reactivate defensive functions, causing tumour regression.

Can it be a coincidence that this method of immunotherapy has been “rediscovered” repeatedly throughout the centuries? Clearly, Coley’s approach to cancer treatment has a place in the past, present, and future. It offers a rare opportunity for the development of a broadly applicable, relatively inexpensive, yet effective treatment for cancer. Even in cases beyond the reach of conventional therapy, there is hope.

Keywords: Dr William Coley; tumour regression; fever; immunosuppression; immunotherapy; macrophages; neoplasms

Abbreviations: BCG, bacillus Calmette-Guerin; IL, interleukin; TNF, tumour necrosis factor

THE BONE SURGEON

“Drugs can only repress symptoms: they cannot eradicate disease. The true remedy for all diseases is Nature’s remedy …. There is at bottom only one genuinely scientific treatment for all diseases, and that is to stimulate the phagocytes. Stimulate the phagocytes. Drugs are a delusion”. So goes the counsel of physician Sir Bloomfield Bonington in George Bernard Shaw’s 1906 play The Doctor’s Dilemma.1 Prophetic words, indeed, that may be the basis for a new paradigm in cancer treatment as we enter the 21st century.

William Coley began his career as a young surgeon at New York Memorial Hospital. Similarly disillusioned with conventional medicine, he wondered whether nature indeed held a cure for cancer. Could he harness the power of the immune system to the benefit of his cancer patients? His search for a new approach began after the loss of his very first patient in 1891. A young woman of 17 had injured her right hand and presented with persistent inflammation and pain. He diagnosed her lesion as a sarcoma of the bone and opted for amputation of her right arm below the elbow. Yet, despite no clinically evident metastases, the patient succumbed to her disease two and a half months after surgery. Shaken by this failure, Coley searched the hospital records for previous cases to learn more about this uncommon disease.

Serendipitously, he discovered the record of an immigrant patient who presented with an egg-size sarcoma on his left cheek.2 The sarcoma was operated on twice and still recurred as a 4.5 inch grape-like cluster below his left ear. The extensive wound after surgery could not be closed and skin grafts were unsuccessful. Ironically, this failure to close the wound would play a key part in the patient’s eventual cure. The tumour progressed and a final operation only partially removed the tumour. The case was considered hopeless. After the last operation, the wound became severely infected with erysipelas (that is, Streptococcus pyogenes) and the patient developed a high fever. Little could be done to stop the infection, yet surprisingly, after each attack of fever the ulcer improved, the tumour shrank, and finally disappeared completely. The patient was discharged four and a half months later. Coley, eager to find this patient, spent weeks searching throughout New York’s lower east side. His efforts were not in vain. The patient, still bearing a large scar from his previous operations, had no trace of cancer and claimed excellent health since his discharge—seven years previously.

Coley suspected that somehow the infection was responsible for this miraculous cure. He resolved to put his theory to the test and infect his next suitable case with erysipelas. In fact, he infected his next 10 patients.2,3 Problems with this approach soon became apparent: sometimes it was difficult to induce an infection, other times there was strong reaction and the disease regressed, however, occasionally the infection was fatal. Due to its unpredictability, he elected to switch to a vaccine containing two killed bacteria:S pyogenes and Serratia marcescens. Experimental work at the time suggested that the latter bacteria increased the virulence of the former.4 In this way, he could simulate an infection (for example, inflammation, chills, fever) without worrying about the risks of an actual infection. This vaccine became known as “Coley’s toxins”. His first case was a success,4 a man bedridden with an inoperable sarcoma involving the abdominal wall, pelvis, and bladder. The disease regressed completely and the patient was followed up until his death from a heart attack 26 years later.5

Coley worked in the Bone Service at the hospital, later becoming its chief in 1915. Thus, the majority of malignancies he treated were sarcomas. Success with Coley’s vaccine, however, was by no means limited to this tumour type. Contrary to what has been suggested by others,6,7 Coley’s vaccine was widely and successfully used by other contemporaries for sarcomas as well as carcinomas, lymphomas, melanomas, and myelomas.5,8–11 A striking feature of his immunotherapy regimen was that even when applied to patients in their final stages of disease some remarkable recoveries were obtained, with patients often outliving their cancer (box 1).5,9–13 Coley himself went on to treat hundreds of patients, and over time, gained an appreciation of how this regimen could be most effectively administered. In fact, Coley was considered to have treated more sarcoma patients than any other physician up to that time.14 Coley considered several points crucial to a patient’s survival.15 First and foremost was to imitate a naturally occurring acute infection, and thus, inducing a fever was essential. Injections were optimally administered daily (or every other day) for the first month or two. To avoid immune tolerance to the vaccine, the dosage was gradually increased over time (depending on patient response). The vaccine was injected directly into the primary tumour and metastases, when accessible. Finally, a minimum six month course of weekly injections was followed to prevent disease recurrence.

Box 1: The country vet
The patient, a veterinary surgeon, was struck over the right superior maxilla by the horn of a bull in February 1901. Several weeks later, he experienced severe pain over the site of injury and to relieve the pain a tooth was pulled. The pain persisted, and in April, the patient was diagnosed as having a mixed cell sarcoma.

Excision of the upper jaw was performed in May. A large tumour was found occupying the maxillary antrum and almost the entire upper jaw. The growth was too extensive for complete removal. There was also an egg-size mass under the left ear. Several days after surgery, the sarcoma began to increase in size, invading the nose and extending along the palate into the pharynx and invading the parotid region.

At this time the patient had difficulty retaining food. His speech was difficult to understand. Although previously able to walk several miles, he now could barely walk from his bed to the door. Jaundice was pronounced; the liver was enlarged. Nausea and vomiting increased. His pulse was between 140–150 beats per minute and was weak and intermittent. Although sceptical, the patient’s physician, O K Winberg agreed to treat him with Coley’s vaccine. In August, starting at a low dose, he gave the patient daily injections while gradually increasing each subsequent dose. Initially, he injected into the upper and lower jaw and later into the abdominal wall. By this time, the patient’s disease progressed to the point where he could no longer take nourishment. He was 113 lbs. The patient had severe abdominal pain; his eyesight began to fail. His teeth became so tightly closed that it was impossible to cleanse his mouth and his speech was almost incomprehensible. He fell into a stupor, but during a brief period of consciousness, he implored to Winberg “either kill me or cure me”.13

Although gradual at first, improvement became increasingly marked after his first fever. Jaundice disappeared after three weeks. By September, he was attending to a large veterinary practice, which often called him away both night and day. By that time the patient weighed 143 lbs. No trace of tumour could be found in the neck, face, or jaw. Abdominal examinations showed nothing abnormal. He continued to receive injections through to January 1902.

The patient remained in good health and free from recurrence until 1907, six years after treatment, when he died of acute nephritis from alcoholic excess.

Shortly before Coley’s death in 1936, Coley’s vaccine received an endorsement in the New and Nonofficial Remedies of the American Medical Association, which stated “its use as a prophylactic in conjunction with conservative or radical surgery” and “inoperable cases may be quite justified”.9 In addition, some textbooks from that period advocated the use of Coley’s vaccine. For example, the 1931 edition of Modern Surgery advised, “after removing a sarcoma in any region, the patient should be given courses of injections of Coley’s fluid”.16 Similarly, in Modern Operative Surgery,17 it is stated for sarcomas that “after amputation, prophylactic injections of Coley’s fluid should be given in doses sufficient to cause a sharp febrile reaction”.

It is often believed that Coley’s vaccine was more effective against sarcomas than carcinomas.18,19 This is due to the fact that Coley primarily treated sarcomas (not surprising considering his specialty) and because Coley initially had less success in treating carcinomas in his early experiments with streptococcus cultures.10 Coley, however, later changed his views as his successes against carcinomas,20–22 and those reported to him by others,5,23 accumulated. In an analysis of 896 patients with microscopically proven malignancy treated with Coley’s vaccine,10 the five year survival for inoperable carcinomas (34%–73%) was similar to inoperable sarcomas (13%–79%), the range varying with tumour subtype.

In an effort to evaluate past successes using Coley’s regimen to that currently observed with modern conventional treatment, a retrospective study compared the 10 year survival rates of patients treated by either method using data from the Surveillance Epidemiology End Result cancer registry.24 Limitations of the study included sample sizes and staging of patients treated with Coley’s vaccine. Still, this study found that despite the billions of dollars spent to develop modern cancer treatments, patients receiving modern conventional therapies did not fare better than patients receiving the treatment initiated by Coley over 100 years ago. Where would cancer treatment be today if equivalent effort and funds had been used to develop a better understanding of the treatment pioneered by Coley? Some answers might be found by taking a closer look at the history of spontaneous regression.

SPONTANEOUS REGRESSION IN HISTORY

Peregrine Laziosi (1265–1345), having been afflicted with cancer himself, was several centuries later canonised and named the patron saint of cancer patients. In the course of his untiring work preaching, converting and reconciling sinners, he noticed a large growth emerging on his leg. The growth on his tibia was pronounced unanimously by the best physicians of his time to be malignant.25 His only option was to have his leg amputated. The lesion grew to the point where it broke through the skin and became severely infected. In fact, it was stated “such a horrible stench was given off that it could be endured by no one sitting by him”.26 Miraculously, by the time he was due to have his operation, his physician was astonished to observe that there were no signs of the tumour. Saint Peregrine’s cancer never returned. Was this spontaneous regression an isolated event or did the infection play a part?

Once Coley’s interest in tumour regression was kindled, he found that spontaneous regression in association with acute infections was often mentioned in the historical literature2 and he was to record many more cases himself.15 Moreover, he discovered that many past physicians had used these infections to the advantage of their patients. Such coincidental infections had in fact inspired a wide variety of rudimentary cancer immunotherapies. The earliest example of such cancer immunotherapy may be thousands of years old. In the writings of the Ebers Papyrus (c 1550 BC), attributed to the great Egyptian physician Imhotep (c 2600 BC), the recommended treatment for tumours (swellings) was a poultice followed by incision.27 Such a regimen would inevitably lead to an infection at the tumour site. By the 1700 and 1800s AD, crude forms of cancer immunotherapy became widely known and accepted.8 For example, Tanchou in his comprehensive treatise on cancer published in 1844, provides insight on how these immunotherapies came into being:”One knows that often the affected lymph nodes and primary growths disappear during the course of concurrent illness, never to return. It is according to that idea … that a large number of observers have advised establishing ‘issues’[suppurating sores] on diverse portions of the body and even in the wounds remaining after operation”.28 He goes on to cite many cases from other physicians where “issues” were successfully established. Other strategies from that era included applying septic dressings to ulcerated tumours,28,29 or deliberately introducing infections such as erysipelas,30,31 gangrene,28,32–34 or syphilis.35,36 Until Coley produced his killed vaccine, using live bacteria to initiate an infection was a precarious gamble between life and death.

The tide began to turn against “Nature’s remedy” for cancer during the 20th century. Firstly, cancer surgery, like any other operation, became a sterile procedure after acceptance of Lister’s aseptic techniques in the late 1800s.37 In fact, in a 1909 discussion paper on cancer treatment,38 one surgeon suggested that the postoperative infections that were common in the past improved survival and should be encouraged. Yet in this new era, his suggestion was harshly criticised as “a doctrine that would make surgery go backwards”. Secondly, by the time of Coley’s death in 1936, radiotherapy had become an established cancer treatment, and chemotherapy was rapidly gaining acceptance. These treatments could be more easily standardised than Coley’s approach and the hope that these therapies would eventually lead to a cure for cancer was high. Such therapies ran counter to immunotherapy, as they are highly immunosuppressive. Thirdly, following World War II, antibiotic use during and after surgery became commonplace. Thus, postsurgical infection rates were reduced even further, in addition to diminishing the severity and duration of those infections that did occur. Finally, once the immune system became “redundant” in fighting infections, antipyretics came into routine use to eliminate the discomforting symptoms of an immune response. Hence, reports of spontaneous regression have become less commonplace, although an association with acute infections is often noted when it occurs.39–50 In fact, a retrospective study by Ruckdeschel et al found that patients who developed empyema after lung cancer surgery had a significantly better five year survival (50%v 18%).51 Nature exists in a delicate balance, the immune system being no exception. Attempts to create an increasingly sterile environment may further reduce our innate cancer curing ability, until we may finally convince ourselves that it never existed at all.

IMMUNE SYSTEM AND DISEASE

Febrile immune response
As mentioned previously, Coley asserted that fever induction was a key aspect of his treatment. In fact, he observed that a strong febrile reaction was the symptom most associated with tumour regression. A retrospective study of patients with inoperable soft tissue sarcomas treated with Coley’s vaccine found a superior five year survival in patients whose fevers averaged 38–40°C, compared with those having little or no fever (

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2 Responses to “Hyperthermia, Fever Therapy for Cancer – a viable alternative”

  1. mitchell Says:

    MY NAME IS MITCHELL FROM MANHATTAN.AND I WAS DOWN WITH BREAST CANCER FOR ABOUT 9MONTHS AND IT REALLY AFFECTED MY LIFE.. I WAS ALREADY ON CHEMO AND I HAD ALREADY LOST HOPE LIKE MOST OF YOU NOW.IT WAS COSTING ME SO MUCH AND I BECAME SO BROKE AND COULDNT WORK.EVEN MY FAMILY GOT TIRED.AND I DIDNT KNOW WHAT ELSE TO TRY SO SOMEONE TOLD ME ABOUT TRYING ALTERNATIVE MEANS THROUGH WHICH SHE GOT CURED.. AND I WAS SKEPTIC ABOUT IT..BUT WHAT CHOICE DID I HAVE. I WAS ALREADY DYING.SO I STARTED USING THIS THERAPY THAT DIDNT COST ME MUCH.IT WAS SOME FORM OF HERBAL MIXTURE WHICH GOES WAY DEEP INTO THE SYSTEM.THE ROOTS AND LEAVES AND HERBS WERE GOTTEN FROM AFRICA . I KEPT USING IT AND WITHIN A FEW MONTHS, I STARTED NOTICING CHANGES, MY HAIR STARTED BECOMING NORMAL AND I COULD WALK AND EAT RIGHT.. I DIDNT NEED CHEMO ANYMORE.. NOW I AM TOTALLY AND COMPLETELY FREE. THE CELLS ARE FINALLY DEAD. ALTHOUGH I AM STILL USING THE THERAPY.THIS IS MY TESTIMONY AND I WANT TO BE OF HELP TO MY FELLOW PEOPLE OUT THERE. I CAN IMAGINE WHAT YOU ARE GOING THROUGH OR WHAT YOU HAVE GONE THROUGH. BUT YOU DONT HAVAE TO GIVE UP OR LOOSE HOPE.I AM A LIVING SURVIVOR. INCASE ANYONE WANTS TO TRY OUT THIS ALTERNATIVE THERAPHY, THE EMAIL ADDRESS OF THE MAN WHO CURED ME IS SPELLSFORBETTERLIFE AT YAHOO DOT COM AND MY OWN EMAIL IS MITCHELL_ANDERSON92 AT YAHOO DOT COM

  2. Graham Says:

    Re Mitchell above – AVOID!!! THIS IS SPAM!!! SEE HIS SIMILAR POST HERE FOR DIFFERENT ILLNESS…

    http://www.trying-to-conceive.com/fertility-clinic/egg-donation-program/

    Only spell coming to get you Mitchell is KARMA!!!!!