Hyperthermia and immunotherapy in the treatment of cancer: the Gorter Model.
|Article Type:||Clinical report|
Immunotherapy (Patient outcomes)
Fever (Physiological aspects)
Fever (Patient outcomes)
Hyperthermia (Physiological aspects)
Hyperthermia (Patient outcomes)
Cancer (Care and treatment)
Cancer (Patient outcomes)
|Publication:||Name: Townsend Letter Publisher: The Townsend Letter Group Audience: General; Professional Format: Magazine/Journal Subject: Health Copyright: COPYRIGHT 2012 The Townsend Letter Group ISSN: 1940-5464|
|Issue:||Date: August-Sept, 2012 Source Issue: 349-350|
|Product:||Product Code: 8000432 Cancer Therapy NAICS Code: 621 Ambulatory Health Care Services|
|Geographic:||Geographic Scope: United States Geographic Code: 1USA United States|
I would cure all diseases if I only could produce fever.
Parmenides, Greek physician, 510 BC
Fever turns out to be one of the missing links in understanding cancer. A growing body of research suggests that most cancer patients have a lower core temperature and cannot mount a fever, and thus are unable to activate their immune system. In the clinical setting, these patients report having never experienced a fever. The research provides strong evidence for this correlation.
Cancer and Fever
An extensive body of research suggests that many cancer patients have a lower core body temperature, typically 0.8[degrees]F (0.5[degrees]C) lower than the average person. There may also be an inconsistent pattern in the rhythm of their temperature over a 24-hour period (as shown in Figure 1).
[FIGURE 1 OMITTED]
In our clinical experience, many of these patients report that they often feel chilly or cold, with cold hands and feet, and that this has been a typical pattern for the past several years. Documenting their actual temperature, we find that their natural circadian rhythm for temperature is absent or disrupted.
Cancer patients also report that they were seldom ill before they developed cancer. They may have experienced brief bouts of a sore throat, a cold, or a cough, but these illnesses were almost never accompanied by a fever. These cancer patients, like most people in industrial societies, habitually use aspirin, acetaminophen, or antibiotics at the first sign of a fever.
Fever as the source of immune activation. When body temperature reaches 101.3[degrees]F (38.5[degrees]C), typically the immune system shifts into a state of intensive activity. At this temperature, immune factors in the bloodstream increase two-fold or more, and in some cases as high as ten-fold, triggering an activation of immune defenses throughout the body. Numerous studies have reported higher levels of messenger chemicals, white blood cells, and immune scavengers in response to fever, reflecting a broad range of immune factors:
* heat shock proteins (2), (3)
* interleukins and other cytokines (4)
* human growth hormones (5)
* antigen-presenting dendritic cells (6)
* lymphocytes such as NK cells (7), (8) and T-cells (6), (9)
* phagocytes such as macrophages (10)
* antibodies (11)
In vitro research at the University of Vienna found a ten-fold increase in monocytes when blood was heated to 102.2[degrees]F (39[degrees]C). (12) The researchers confirmed that this increase was associated with higher levels of heat shock proteins in the bloodstream.
Fever: foe or friend? In our culture, there is a pervasive fear of fever, a tendency to see fever as the cause of illness rather than the body's natural mechanism for healing. While fever racks the patient, the mother, father, friend, or caretaker stands by feeling powerless. No wonder it is a temptation to quickly reach for medication such as aspirin or Tylenol[TM] at the first sign of a fever. The medicine represents hope and recovery. Giving medication implies a cure. (And so does the advertising. The message is: If you can just reduce the fever, the disease will go away.)
Ironically, the fear of fever is misplaced. Unless the fever is too high, above 104[degrees]F (40.0[degrees]C), or persists for weeks at a time, no harm occurs. In fact, fever is the natural response of all mammals to infection and illness. Research has made it clear that fever is not the enemy; it is the friend of healing. This scientific rationale, supported by thousands of research studies, provides the basis for hyperthermia treatment at the Medical Center Cologne and other medical centers in Europe and worldwide.
Conditioning the fever response. Surprisingly, the immune system can be trained to turn on or off in response to repeated cues--for example, in reaction to certain medications. This trained or "conditioned" response was demonstrated in the work of Dr. Robert Ader and colleagues, published over a period of more than 25 years. (13), (14), (15), (16) Researchers found that the immune system could actually be deactivated through "classical conditioning."
Applying this concept to the use of fever suppressing medications with children, the implication is that over time the fever response can be permanently inactivated by the frequent use of these medications. From that point on, whenever the child develops a fever, the fever process is aborted. With frequent use of fever suppressants in childhood, the immune system may never become fully activated and mature. The immune system is prevented opportunities for a "workout" and becomes less and less adept, leaving the body more vulnerable.
Without an all-out effort by the immune system to completely wipe out an infection, bacterial and viral infections can linger and become chronic. The association of chronic infection with cancer is well documented for conditions that include human papilloma virus and cervical cancer, hepatitis and liver cancer, and H. pylori bacteria and gastric cancer. These factors appear to set the stage for the development of cancer.
Fever as the missing link in cancer. One of the most insightful looks at the role of fever in healing comes from work published by the National Institutes of Health. Researchers performed an in-depth review of the medical literature on cancer risk. They reported that risk appears to be increased in individuals who have a history of fewer infections, noting "an inverse correlation between the incidence of infectious diseases and cancer risk." (17) In sum, people who have not experienced common childhood illness and fever apparently have a greater risk of cancer.
Averting fever with the frequent use of aspirin, acetaminophen, or antibiotics may actually impair immune function. The research team concluded that "the occurrence of fever in childhood or adulthood may protect against the later onset of malignant disease." (18), (19) Researchers also pointed out that "spontaneous remissions are often preceded by feverish infections." (18), (19) Their final report on the correlation between fever suppression and cancer includes more than 750 references from the medical and research literature. (20)
A century of research on cancer and fever. A number of researchers have tracked this issue in large clinical trials over the past 100 years, starting with published reports in 1854 that many cancer patients exhibited a "remarkable disease-free history." (21) Several later studies confirmed this, reporting that people who developed cancer were rarely ill before their disease.
Studies on the importance of fever as an immune defense against cancer were published in the medical literature in 1854, 1910, 1934, and 1936, each study involving hundreds of patients. Researchers consistently found increased cancer risk for patients who had no history of infectious illness or fever. (20) The majority of more recent studies have corroborated these findings.
* German research published in 1983 found that cancer risk more than doubled in patients who had not experienced major infectious diseases (2.6 times greater risk). Cancer risk was almost 6-fold higher in patients who had never experienced the common cold (5.7 odds ratio), and there was a 15-fold increase for those who had never experienced fever (15.1 odds ratio). (22)
* A study of skin cancer patients, published in Melanoma Research in 1992, reviewed the medical histories of 500 comparable patients, with and without cancer. Researchers found that the patients who had experienced infections accompanied by fever had a much lower incidence of malignant melanoma. (23)
* Research published in the journal Cancer in 1992 evaluated the medical histories of more than 200 patients with brain tumors, who were compared with more than 400 similar noncancerous patients. Those who had experienced infections and colds had a 70% lower risk of cancer. (24)
* In a randomized control trial of 572 critically ill patients, published in 2005 in Surgical Infections, 82 patients with high fever were evaluated in further study. Half of these patients received aggressive fever suppression, and the other half were advised to assume watchful waiting. There were seven deaths in the aggressive group, and only one death in the watchful waiting group. (25)
* In a recent study of 400 hospitalized pneumonia patients, the British Medical Journal reported that the more feverish the patient on admission, the better their chance of 30-day survival. Of patients admitted with a low core temperature, <96.8[degrees]F (36[degrees]C), the data show that 34% died; among those with higher than normal core temperature, above 100.4[degrees]F (38[degrees]C), only 17% died within 30 days of admission. (26)
These studies and hundreds of others demonstrate that fever suppression tends to inhibit the immune response and healing. The research also suggests that when fever is tolerated by the patient through careful watchful monitoring, frequently that improves outcome.
Heat Therapy and Hyperthermia
Fever and heat therapy have been recognized for their beneficial effects on health since antiquity. Ancient Greek medicine, Roman sulfur hot baths, Finnish saunas, European and American spa treatment, Japanese hot tubs, Native American sweat lodges, and therapeutic hot springs worldwide are examples of simple forms of heat therapy as a means of cleansing and healing.
Limitations of traditional heat therapies. We know from systematic studies in the literature that traditional methods such as saunas, mineral baths, and hot tubs do not significantly increase core temperature, nor do they achieve temperatures that correspond to internally induced fever. Consequently, a more innovative approach is necessary to raise the body to a therapeutic fever range. This article will discuss contemporary innovations in hyperthermia, as applied in the treatment of cancer.
A study at the Medical University of Hannover, Germany, found that when body temperature was raised via warm baths, gradually heated to 107[degrees]F (42[degrees]C), core temperature actually increased less than 1[degrees]F (0.4[degrees]C) above normal. (32) Elevated body temperature alone does not automatically induce the immune response, demonstrated in a study in Hamburg, Germany. The temperature of cancer patients was increased with hyperthermia and compared with that of healthy volunteers who took part in strenuous physical exercise to raise their temperature. Although participants in both groups experienced elevated temperature, immune function increased in the cancer patients, but not in the healthy volunteers. Elevated immune factors in cancer patients included human growth hormone and the induction of natural killer cells and T-cells. (30)
Medical hyperthermia. Induced fever or hyperthermia has been studied in hundreds of cancer clinical trials and discussed in thousands of peer-reviewed articles. Research on hyperthermia, also referred to as "fever-range total-body hyperthermia" or "moderate whole-body hyperthermia," has been performed in medical schools and research centers since the 1980s. These studies have been conducted primarily in the U.S., in Germany, across Europe, and in Japan. American research has been conducted in FDA-approved studies at the Mayo Clinic, University of Pennsylvania, University of Texas, and Duke. The medical literature reflects a global dialogue between researchers that has systematically defined effective hyperthermia.
Safety and effectiveness. Hyperthermia has been studied for the treatment of chronic pain, recurrent respiratory infections, asthma, urinary tract infections, and immune deficiency. Induced hyperthermia was first evaluated in animal models 25 years ago, and then in human subjects over the past 20 years, both in cancer patients and in healthy volunteers. (27), (28), (29) Initial studies explored the most effective ways to administer the therapy, defining the length of treatment, (30) heat sources, (31) optimal temperatures, (32) and effects produced. Treatment has been applied as a freestanding therapy; in combination with immune therapies such as dendritic cell injections; (6) and in tandem with conventional therapies such as radiation, (33) chemotherapy, (34) or hormone therapy. (7) Two decades of research have shown that hyperthermia is a safe procedure for the greater majority of patients and for many types of cancer. (27), (28)
Treatment without side effects. Researchers at the Roswell Park Cancer Institute in Buffalo, New York, report that total-body hyperthermia treatments are "well tolerated, with no significant adverse events related to cardiac, hepatic, renal, or pulmonary systems." (29) A German study of hyperthermia for pain in fibromyalgia patients tracked safety and effectiveness. "Side effects were observed in 14 of 69 participants (20%), but all disappeared in less than 30 minutes." (35) The study found that hyperthermia combined with standard multimodal rehabilitation was significantly more effective than standard therapy alone in terms of reducing pain intensity, while improving quality of life.
Hyperthermia and conventional treatment. Both whole-body hyperthermia and regional hyperthermia increase the success rate of radiation (33), (36) and chemotherapy. (34) This combination therapy often results in fewer side effects than chemotherapy or radiation alone. A study conducted at a medical center in the Netherlands tracked the progress of 378 cancer patients receiving hyperthermia in combination with radiation treatments. Over an eight-year time period, a positive response was achieved in 77% of patients. At five years, the disease-specific survival rate was 47%, which is exceptional in cancer treatment. Toxicity was an issue for 12% of patients. Researchers concluded that in addition to diagnosis, "the number of hyperthermia treatments emerged as a predictor of positive outcome." (35)
Development of the Gorter Model
Hyperthermia is one of the primary approaches to treatment provided at the Medical Center Cologne. The Center was founded by Robert Gorter, MD, PhD, and has been under his direction for the past 12 years. Immune supportive therapies are provided in a treatment model developed by Dr. Gorter. These protocols have evolved from his understanding of immune function, garnered in his work as UCSF program director of AIDS research and his background as a clinical oncologist, as well as from his personal experiences as a cancer survivor himself.
Dr. Gorter earned his medical degree at the University of Amsterdam Medical School in the Netherlands. He subsequently opened a private practice and health center in the heart of Amsterdam, but a few weeks later he was diagnosed with far-advanced stage IV testicular cancer--at that time described as "teratocarcinoma," a type of cancer currently defined as "germ cell carcinoma." He was able to recover successfully through nontoxic treatment, without the use of chemotherapy or radiation. His treatment consisted solely of hyperthermia and injections of a known oncologic botanical, European mistletoe. This experience has motivated him to explore new, nontoxic approaches to cancer therapy and has inspired his lifelong work as a researcher and clinician in the area of integrative cancer oncology.
His exploration of immunotherapy deepened with his appointment as physician and researcher on AIDS at San Francisco General Hospital in the world-renowned Ward 86 in the 1980s. When Ward 86 became part of the UCSF AIDS program, Dr. Gorter was appointed medical director of the Department of AIDS Epidemiology and Biostatistics at UCSF, and led that department for four years. Much of what we know today about the progression of HIV infection into AIDS comes from the seminal research on this initial cohort of patients whose progress was tracked in long-term follow-up studies at UCSF. Dr. Gorter was intrigued by the fact that a few of the patients with HIV infection never progressed to AIDS or AIDS-Related Complex (ARC), patients described as "long-term non-progressors."
This work, conducted at the beginning of the AIDS epidemic in the U.S. and E.U., provided Dr. Gorter the opportunity to be involved in the research and clinical care that first defined the complex elements of the human immune system. These studies from UCSF Medical Center have resulted in the most extensive knowledge base on immunity in HIV infection in our time. Dr. Gorier noticed that most of the illnesses leading to the death of HIV-infected patients were malignancies. The resulting deterioration of the immune system and of T-cell activity appeared to correlate with an increase in various forms of cancer.
A decade later, when Dr. Goiter shifted the focus of his work to cancer treatment, he began developing treatment protocols based on the principles of intensive and targeted immune restoration learned in the "war on AIDS." Dr. Gorter has spent more than two decades establishing and refining effective methodology for immune therapy. He has pioneered the integrated use of hyperthermia to reactivate the immune system, in combination with dendritic cell vaccination, which restores and activates T-cells. These therapies are augmented with treatment using mistletoe botanicals, IV antioxidants, and other immune restorative agents. Mistletoe, for example, is known to balance biological rhythms in the body and helps to reestablish the fever response. Components of these approaches to treatment have also been independently studied in hundreds of clinical trials conducted at research centers worldwide.
Whole-Body Hyperthermia: Gorter Model
To date, the majority of the research on hyperthermia has been performed in Germany. At the Medical Center Cologne, located in a large teaching hospital in Cologne, Germany, hyperthermia protocol development has been ongoing under the direction of Dr. Gorter. Over the past 25 years, he has carefully calibrated every aspect of these procedures for maximum safety and benefit. This model is described in detail in the book Fighting Cancer: A Nontoxic Approach to Treatment. (1)
To reactivate immune function in cancer patients, the Gorter Model uses a controlled fever process in which the entire body is gradually heated with infrared light to a moderate fever temperature of 101[degrees]F to 103[degrees]F (38.5[degrees]C to 39.5[degrees]C) under carefully monitored conditions. These treatments engage the patient's immune system, replicating the natural process of fever, comparable to immune activation in response to an acute infection.
Safety. This therapy is accomplished with almost no disruption or side effects--patients typically experience less than one day of mild flulike symptoms. Once patients complete hyperthermia treatment, they feel cleansed and energized. In many cases, this treatment is provided as the first stage of the protocol to engage the immune system. The Gorter approach to whole-body hyperthermia is distinguished by a number of features:
* moderate temperatures
* state-of-the-science equipment
* heart rate monitoring at all times
* an electrolyte IV solution throughout the procedure to maintain hydration
* Safe, optimal infrared electro-hyperthermia technology developed by the German company Celsius 42
* dendritic cell injections at timed intervals, usually directly after hyperthermia
* integrative therapies in an individualized program
Protocol. The patient lies within a tentlike hyperthermia chamber with his or her head outside the chamber. The body is heated by specially designed infrared lamps. (Infrared consists of invisible light waves close to those of visible light on the spectrum and is the primary form of energy received from the sun.) During hyperthermia, the infrared rays warm blood vessels close to the surface of the skin. As the temperature in the skin rises, the temperature of blood in surface capillaries is elevated, circulation increases, and the warmth spreads throughout the body.
With the increase in core temperature, the patient begins to perspire. However, in the closed hyperthermia chamber, evaporation is reduced (as shown in Figures 2 and 3). Transpiration and perspiration lead to cooling only when water can be evaporated. Without the process of evaporative cooling, body temperature continues to increase, raising core temperature and inducing a feverlike state. Once the temperature of 103[degrees]F (39.5[degrees]C) is achieved and maintained for one to two hours, the fever is gradually reduced over the course of another hour or two.
[FIGURE 2, 3 OMITTED]
Controlling temperature. This induced fever is maintained at a moderate temperature to safeguard the well-being of the patient. Maximum temperatures range from 101[degrees]F to 103[degrees]F (38.5[degrees]C to 39.5[degrees]C). In contrast to the Gorter Model, many of the research studies have used maximum temperatures of approximately 107.5[degrees]F (41.8[degrees] to 42[degrees]C). In some studies, patients were anesthetized so they could tolerate the high temperatures. Unnecessary anesthesia is always to be avoided, since it can induce senility in older patients, a phenomenon known as Sundowner Syndrome. General anesthesia is also frequently immune suppressive, and therefore should be minimized or avoided with cancer patients.
Contraindications. At the Medical Center Cologne, total-body hyperthermia is provided to approximately 70% of all patients. Those with a history of heart disease or brain tumors must be carefully screened. Because total-body hyperthermia can cause a certain amount of stress to the system, it is usually not provided to patients with documented cardiac decompensation or those with brain cancer because the therapy can potentially evoke cardiac difficulties or an epileptic seizure. For almost all other patients, total-body hyperthermia has no known negative side effects.
Dendritic cell immunotherapy. Hyperthermia (like fever) activates Natural Killer cells (NK cells), which play an important role in destroying malignant cells. (37) To further engage the immune system, dendritic cell therapy is provided to also activate T-cells. (6)
Dendritic cells are cultured in a medical laboratory from the patient's own white blood cells during the days preceding hyperthermia and are given by injection (as shown in Figure 4, p. 88) directly following the treatment. These dendritic cells have an antigen-presenting function--they hold in "memory" the identity (antigen profile) of the malignant cells. A small injection conveys millions of vital, activated dendritic cells, which then educate the patient's own T-cells to search for and destroy abnormal malignant cells. Acting in concert, the increased number of dendritic cells, activated T-cells, and NK cells have inhibitory effects on tumor growth. (38)
[FIGURE 4 OMITTED]
After the injection, patients typically experience mild flulike symptoms for 6 to 12 hours. These symptoms indicate the activation of the body's healing response. Once the symptoms subside, almost all patients report less pain than before the treatment, and a sense of well-being. It has been observed that patients who react with flulike symptoms after the vaccination with dendritic cells clearly do better and show more benefit from the therapy than those patients who do not experience this response. All patients who achieved complete remission have experienced flulike symptoms.
Once the immune system is engaged, the body begins destroying cancer cells from within. This reduces the need for medication and stabilizes the body against further deterioration. These gains provide the basis for a sense of well-being in the patient, and improve health and healing, even in many patients with stage III and IV cancers. In a broad review of the literature by the authors, the majority of studies reported a stabilizing therapeutic response in more than 50% of patients who received whole-body hyperthermia--typically 56% to 80% of those treated.
Gorter treatment outcomes for breast cancer. The following outcomes data summarizes follow-up for 292 Medical Center Cologne patients with stage III and IV advanced metastatic breast cancer (patients who had been advised that they had no further standard treatment options). Typical integrative treatment for breast cancer includes whole-body hyperthermia, dendritic cell therapy, mistletoe, and other types of immunotherapy, as well as improved diet and other lifestyle changes. All patients received at least three cycles of dendritic cell therapy.
Advanced stage III--IV metastatic breast cancer patients, five years after treatment, N=292
15% (N=45) 100% complete remission
53% (N=156) partial remission
17% (N=50) progression of cancer and death
14% (N=41) lost to follow-up
Case history: breast cancer. When I was diagnosed with malignancies for the fourth time, I decided to go to Germany for treatment at the Cologne Medical Center. I had been diagnosed with breast cancer in 1999, and one of my breasts was surgically removed at that time, but I declined radiation or chemotherapy. After careful thought, I decided to do a nontoxic follow-up treatment, but I also went back to the hospital for periodic check-ups. For the next six years, I was in remission. But at that point, I developed bone cancer. I beat it a second time, but the cancer came back again.
That is when I went to see Dr. Gorter. I improved very quickly with the treatment at Cologne--a combination of hyperthermia and dendritic cell therapy. The pain disappeared very quickly and I was soon pain-free. Walking had become difficult, because moving hurt so much. With this treatment, the pain remains gone and I can walk again. Not all the tumors are gone. Bu the pain is gone and I feel good about it. Iedje Abbenhuis, Belgium, five-year survivor of breast cancer with a previous history of recurring bone and liver metastasis
Localized Hyperthermia: Gorter Model
To localize treatment for areas of the body such as the breast or brain, "regional" hyperthermia is provided. This therapy can be used to selectively heat a specific area of the body, such as a tumor site. Surrounding healthy cells are unaffected. At the Medical Center Cologne, this approach is used with approximately 99% of patients.
Research. To date, there are more than 3000 articles in the medical literature listed under "regional hyperthermia." In conventional oncology, the majority of studies have evaluated local hyperthermia in combination with chemotherapy or radiation. Over 330 clinical trials have been conducted in countries worldwide, across Europe, and in Asia and Israel. Extensive research has been performed at the National Cancer Research Center in Heidelberg, Germany, for more than two decades, and at the National Cancer Institute in Rome. American studies include research at the Anderson Cancer Center in Houston, at Duke, and at Wake Forest.
In a review by the authors of 50 recent clinical trials, 60% of the studies involved the use of localized hyperthermia in combination with chemotherapy. The majority of the other studies evaluated targeted hyperthermia with surgery or radiation. Other major studies assessed hyperthermia and immunotherapy (primarily INF-[alpha]) provided in tandem. Combining any of these therapies with localized hyperthermia appears to increase effectiveness, with fewer side effects. However, only a handful of large clinical trials have focused on localized hyperthermia as a stand-alone treatment, perhaps due to the lack of economic incentives.
Mechanism. Tumor cells produce abnormal tumor-specific proteins, which are thousands of times larger than normal proteins. During hyperthermia, these tumor proteins absorb energy when exposed to an MRI-like electromagnetic field. This causes the malignant cells to heat up to an extremely high temperature, 107.6[degrees]F (42[degrees]C). As a result of elevated temperatures, cancer cells increase their metabolism and lactic acid production. As metabolism speeds up within tumor cells, they essentially self-destruct and drown in the lactic acid they produce, resulting in cell death (necrosis). Localized high temperature and the resulting death of cancerous cells simultaneously activate the immune system. Neighboring healthy cells are unaffected and remain at normal body temperature.
Safety protocol. Electro-hyperthermia equipment used for localized hyperthermia in the Gorter Model causes no risk of burns and can be focused exclusively on any area of the body. Tumor cells can be heated selectively, because they have a much higher electromagnetic resistance than normal cells. This makes possible interventions for areas of the body that would normally be difficult to treat, such as the head, lungs, and bone tissue (see Figure 5).
[FIGURE 5 OMITTED]
The fact that hyperthermia can be efficacious in treating brain tumors was borne out by a recent phase Ill study for patients with brain lesions, in which hyperthermia proved to support significantly better results in illness-free time and survival when compared with radiation and/or medication alone. Localized heat treatment is provided in the Gorter Model to all patients who have solid tumors.
Integrative treatment. Localized hyperthermia is a highly effective means of destroying cancer cells without causing toxicity, particularly when used in conjunction with other immune supportive therapies such as vitamin C infusions, thymus peptides, and mistletoe extract. Most patients receiving localized hyperthermia are provided with dendritic cell injections, since the heating process makes cancer cells more vulnerable to destruction by the immune system.
Gorter treatment outcomes: brain cancer. At the Medical Center Cologne, even patients with primary or secondary brain tumors or metastases of the breast or lung are successfully treated without any side effects using this approach. The research shows that 44% of all patients with stage IV glioblastoma multiforme go into complete, long-term remission, following a protocol of at least three dendritic cell vaccinations and 24 sessions of local hyperthermia. This is a highly promising outcome, since with conventional treatment approximately 72% of patients with brain tumors (glioblastoma multiforme stage IV) die within the first year after diagnosis, and only 1% survive for three years.
Case history: brain cancer (recurrent glioblastoma multiforme stage IV). Twenty years ago, Teun van Vliet was twice an indoor world champion cyclist and in 1988 wore the yellow jersey in the Tour de France. In 2001 he was diagnosed with a brain tumor, and in 2006 an inoperable recurrence of the tumor was detected. Teun had another round of brain surgery ("debulking") and also received radiation treatment. This caused him to lose his power of speech, and to some degree he also lost memory and coordination. Within conventional oncology, nothing more could be done for him, and he was told that he had less than six months left to live. Teun and his partner decided to seek a second opinion, and they went to Cologne to consult with Dr. Gorter, who advised him to try localized hyperthermia in combination with immune therapy. Teun's partner soon reported beneficial changes in his health.
"The first thing we noticed about these treatments was that they really improved his speech. He is much more lively; more active. I have my old buddy back, really. When he comes home from Cologne, his speech has improved, his motor skills have improved, he feels more energetic. Nothing but improvements. The quality of his life is definitely better." Partner of Teun van Vliet, Tour de France champion cyclist, patient at the Medical Center Cologne, and survivor of stage IV brain cancer. In April 2012, a new MRI scan confirmed that there was still no recurrence of the cancer, and Teun has been clinically cancer-free for more than six years.
The Importance of an Integrative Approach
We believe that the noninvasive support provided by this protocol is an ideal adjunct to many treatment programs, because it does not increase the level of toxicity in the body or the immune burden, nor is it invasive. Hyperthermia can be provided in combination with a range of other therapies, both integrative and conventional.
What makes this approach unique is the calibrated timing of hyperthermia and the dendritic cell vaccinations, which are augmented with other elements of the program, such as IV antioxidants, subcutaneous mistletoe injections, diet, and other lifestyle changes. The favorable outcomes indicate that in this protocol, the sum of the whole is greater than the parts. This form of treatment does not promise cure, but it does offer the possibility of improvement. The majority of stage IV patients experience significantly longer survival with greater quality of life.
Several other elements contribute to the success of this therapy. The program tends to attract patients who are proactive: they chose to seek help, and they have a will to live. In addition, Dr. Gorter serves as a positive role model, because he is a cancer survivor. This provides a legitimate nonverbal cue that hope is possible. Much of what he is suggesting to patients he has actually experienced and applied in his own healing.
We predict that the next phase of this integrative approach will focus on patients at a much earlier stage in disease progression. Given the low toxicity and the potential effectiveness of immunotherapy, this treatment would be highly appropriate for patients who are advised to observe watchful waiting.
Medical Center Cologne
50677 Cologne | Germany
Phone: +49 221 788030
Fax: +49 221 78803250
Business hours: Monday-Saturday, 8 am-6 pm Videos of patient interviews and additional information on the integrative therapies discussed in this article are available online.
Dendritic Cell Therapy
In the US, a form of dendritic cell therapy has been granted FDA approval for the treatment of prostate cancer, marketed under the name Provenge. The manufacturer, Dendreon, has also begun clinical trials for dendritic cell therapy in the treatment of bladder cancer. Note that this therapy may differ significantly from that described in this article.
See: www.Provenge.com and select "Find a Provenge[TM] provider."
Localized (Regional) Hyperthermia
Localized hyperthermia and Provenge[TM] dendritic cell therapy are offered as separate protocols through Cancer Treatment Centers of America. Note that this therapy may differ significantly from that described in this article.
(1.) Adapted text from Fighting Cancer: A Nontoxic Approach to Treatment by Robert Gorter and Erik Peper, copyright [c] 2011 by Robert Goiter and Erik Peper, is reprinted by permission of North Atlantic Books. [ISBN 978-1-58394248-2]
(2.) Oehler R, Pusch E, Zellner M, et al. Cell type-specific variations in the induction of hsp70 in human leukocytes by feverlike whole body hyperthermia. Cell Stress Chaperones. 2001;6(4):306-315.
(3.) Dressel R, Heine L, Elsner L, et al. Induction of heat shock protein 70 genes in human lymphocytes during fever therapy. Ear J Clin Invest. 1996;26(6):499--505.
(4.) Robins HI, Kutz M, Wiedemann GJ, et al. Cytokine induction by 41.8 [degrees]C whole body hyperthermia. Cancer Letters. 1995;97(1 2):195-201.
(5.) Rhind SG, Gannon GA, Shephard RJ, Buguet A, Shek PN, Radomski MW. Cytokine induction during exertional hyperthermia is abolished by core temperature clamping: neuroendocrine regulatory mechanisms. Int J Hyperthermia. 2004;20(5):503-16.
(6.) Bedrosian I, Mick R, Xu S, et al. Intranodal administration of peptide-pulsed mature dendritic cell vaccines results in superior CD8+ T-cell function in melanoma patients. J Clin Oncol. 2003 Oct 15;21(20):3826-3835.
(7.) Kappel M, Poulsen TD, Hansen MB, Galbo H, Pedersen BK. Somatostatin attenuates the hyperthermia-induced increase in neurtrophil concentration. Euro J Appl Physiol Occup Physiol. 1998; 77(1-2):149-56.
(8.) Evans SS, Chen Q, Fisher DT, et al. Fever-range thermal stress promotes lymphocyte trafficking across high endothelial venules via an interleukin 6 trans-signaling mechanism. Nat Immunol. 2006; 7(12):1299-308
(9.) Atanackovic D, Nierhaus A, Neumeier M, Hossfeld DK, Hegewisch-Becker S. 41.8[degrees]C whole-body hyperthermia as an adjunct to chemotherapy induces prolonged T-cell activation in patients with various malignant diseases. Cancer Immunol Immunother. 2002;51(11-12):603-613.
(10.) Alexander P. Evans R. Endotoxin and Double stranded RNA render macrophages cytotoxic. Nature New Biol. 1971;232:76-78
(11.) Roberts NJ Jr. Impact of temperature elevation on immunologic defenses. Rev Infect Dis. 1991;13(3):462-72.
(12.) Zellner M, et al. Human monocyte stimulation by experimental whole body hyperthermia [in German]. Wien Kiln Wochenschr. 2002 Feb 15;114(3):102-107.
(13.) Ader R, Cohen N. Behaviorally conditioned immunosuppression. Psychosom Med. 1975;37(4):333-340.
(14.) Ader R. Conditioned immunomodulation: research needs and directions. Brain Behav Immun. 2003;17, Suppl 1:S51-7.
(15.) Goebel MU, Trebst AE, Steiner J, et al. Behavioral conditioning of immunosuppression is possible in humans. The FASEB Journal. 2002;16:1869-1873.
(16.) Hiramoto R, Rogers C, Demissie S, et al. The use of conditioning to probe for CNS pathways that regulate fever and NK cell activity. Int J Neurosci. 1996;84(1-4):229-45.
(17.) Kleef R, Jonas WB, Knogler W, et al. Fever, cancer incidence and spontaneous remissions. Neuroimmunomodulation. 2001;9(2):55-64.
(18.) Kleef R, Jonas WB, Knogler W, Stenzinger W. Fever, cancer incidence, and spontaneous remissions. Neuroimmunomodulation. 2001;9(2):55-64.
(19.) Kleef R, Hager ED. Incidence of malignancies and missing history of fever. In: Hyperthermia in Cancer Treatment: A Primer, Baronzio GF, Hager ED, eds. New York: Springer US; 2006.
(20.) Kleef R, Hager ED. Fever, Pyrogens and Cancer. Austin, TX: Landes Bioscience; 2000. Epub: NCBI. Madame Curie Bioscience Database (internet); 2000. Available at http://www.ncbi.nlm.nih.gov/books/NBK6084/. Accessed 05-05-12.
(21.) Laurence JZ. The diagnosis of surgical cancer (Lister Prize, 1854). London: Churchill. 1854:56.
(22.) Remy W, Hammerschmidt K, Zanker KS, et al. Cancer patients rarely have a history of infection [in German]. Med Klinik. 1983;78:95-98.
(23.) Kolmel K, Gefeller O, Haverkamp B. Febrile infections and malignant melanoma: results of a case-control study. Melanoma Res. 1992;2:207-211.
(24.) Schlehofer B, Blettner M, Becker N, et al. Medical risk factors and development of brain tumors. Cancer. 1992;69:2541-2547.
(25.) Schulman Cl, Namias N, Doherty J, et al. The effect of antipyretic therapy upon outcomes in critically ill patients: a randomized, prospective study. Surg Infect. 2005;6(4):369-375.
(26.) Barlow G, Lillie P, Nathwani D, Davey P. Fever as nature's engine: some clinical data. BMJ. 2010 Feb 16;340:c905.
(27.) Dietzel F. Basic principles in hyperthermic tumor therapy. Recent Respite Cancer Res. 1983;86:177-190.
(28.) Kerner T, Deja M, Ahlers 0, et al. Whole-body hyperthermia: a secure procedure for patients with various malignancies? Intensive Care Med. 1999;25(9):959-965.
(29.) Kraybill WG, Olenki T, Evans SS, et al. A phase I study of fever-range whole body hyperthermia (FR-WBH) in patients with advanced solid tumours: correlation with mouse models. Int J Hyperthermia. 2002;18(3):253-266.
(30.) Atanackovic D, Pollok K, Faltz C, et al. Patients with solid tumors treated with high-temperature whole-body hyperthermia show a redistribution of naive/memory T-cell subtypes. Am J Physiol Regul Integr Comp Physiol. 2006;290(3):R585-594. Epub 2005 Oct 27.
(31.) Wehner H, von Arden A, Kaltofen S. Whole-body hyperthermia with water-filtered infrared radiation: technical-physical aspects and clinical experiences. Int J Hyperthermia. 2001;17(1):19-30.
(32.) Doering TJ, Aaslid R, Steuernagel B, et al. Cerebral autoregulation during whole-body hyperthermia and hyperthermia stimulus. Am J Phys Med Rehabil. 1999;78(1):33-38.
(33.) Franckena M, Lutgens LC, Koper PC, et al. Radiotherapy and hyperthermia for treatment of primary locally advanced cervix cancer: results in 378 patients. Int J Radial Oncol Biol Phys. 2009;73(1):242-50. Epub 2008 Nov 5.
(34.) Bull JM, Scott GL, Strebel FR, et al. Fever-range whole-body thermal therapy combined with cisplatin, gemcitabine, and daily interferon-a: description of a phase I-II protocol. Int J Hyperthermia. 2008 Dec;24(8):649-662.
(35.) Brockow T, Wagner A, Franke A, Offenbacher M, Resch KL. A randomized controlled trial on the effectiveness of mild water-filtered near infrared whole-body hyperthermia as an adjunct to a standard multimodal rehabilitation in the treatment of fibromyalgia. Clin J Pain. 2007;23(1):67-75.
(36.) Westermann AM, Jones EL, Schem BC, et al. First results of triple-modality treatment combining radiotherapy, chemotherapy, and hyperthermia for the treatment of patients with Stage IIB, III, and IVA cervical carcinoma. Cancer. 2005;104(4):763-770.
(37.) Kappel M, Poulsen TD, Galbo H, Pedersen BK. Influence of minor increases in plasma catecholamines on natural killer cell activity. Horm Res. 1998:49(1):22-26.
(38.) Wust P, Riess H, Hildebrandt B, et al. Feasibility and analysis of thermal parameters for the whole-body-hyperthermia system IRATHERM-2000. Int J Hyperthermia. 2000;16(4):325-339.
by Robert Gorter, MD, PhD, and Erik Peper, PhD
About the Editor
We thank Nancy Faass for her superb work as editor and her thorough research of the literature. A writer and editor in San Francisco, she has worked on more than 40 books for publishers that include Elsevier, Harper, McGraw-Hill, Mosby, New Harbinger, New World Library, North Atlantic, and others. Director of The Writers' Group, her work includes articles, white papers, and writing for the Web. For more information, see www.HealthWritersGroup.com.
About Robert Gorter, MD, PhD
Dr. Gorter trained in Amsterdam and for ten years served as physician, researcher, and then medical director of the Department of AIDS Epidemiology and Biostatistics, University of California, San Francisco Medical School, a department that provided world leadership in defining and treating AIDS. He has spent the past 25 years applying lessons learned from the AIDS epidemic and the emerging field of immunotherapy in the treatment of cancer. Dr. Goiter served as a full UCSF faculty member from 1986 until 2008. He also holds a PhD from the University of Witten/Herdecke in Germany in 1993, where he continues to serve as full faculty member. He holds a medical degree in conventional Western medicine with postdoctoral work in the U.S. He has also completed specialty training in anthroposophical medicine in Switzerland with an emphasis on oncology. For additional biographical information on Dr. Gorter, see the section "Development of the Garter Model," earlier in this article. For more information on the Medical Center Cologne and for video interviews of patients in long-term remission, see www.medical-center-cologne.com.
About Erik Peper, PhD
Erik Peper is an internationally known expert on holistic health, stress management, and biofeedback. He received his BA from Harvard University in 1968 and his PhD in psychology from Union Graduate Institute in 1975. Since 1976 he has taught at San Francisco State University (SFSU), where he has been instrumental in establishing the Institute for Holistic Health Studies, the first program in holistic health at a public university in the U.S. Dr. Peper is president of the Biofeedback Foundation of Europe and former president of the Biofeedback Society of America (Association for Applied Psychophysiology and Biofeedback). He served as sports psychologist for the U.S. Olympic Gymnastics Team for four years, and his expertise includes peak performance and stress management. He is also a recognized expert on workplace health and computer-related injuries, and received a State of California Governor's Employee Safety Award in 2004 for his work in these areas.
Dr. Peper has written more than 100 articles and nine books, including Make Health Happen, Biofeedback Mastery: An Experiential Teaching and Self-Training Manual, and Fighting Cancer: A Nontoxic Approach, coauthored with Dr. Gorter. In addition to teaching, research, consulting, and travel, he maintains a biofeedback practice in Berkeley, California. For additional information, see www.biofeedbackhealth.org and his blog site, www.peperperspective.com.
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