Fever-range, total-body hyperthermia

Fever-range, total-body hyperthermia has the role to restart the immune system. Practically all cancer patient have a lower than average core temperature and are unable to develop a fever—thus they are unable to activate their immune system. To reactivate immune function, a controlled fever is induced to artificially heat the body—this process is known as therapeutic fever.
Fever-range, total-body hyperthermia is non-toxic treatment that is often linked to improved temperature regulation in the body.
The treatment is well-tolerated by practically all patients, and can be provided in combination with a range of other therapies. In the past 25 years, more than 1,000 clinical trials and thousands of scientific articles have been published on induced total-body hyperthermia and localized hyperthermia in the peer-reviewed medical literature. Hyperthermia has also been studied for chronic pain, asthma, and other chronic or recurrent respiratory infections, urinary tract infections, and immune deficiency.
More than 700 research studies have focused specifically on cancer treatment using total body hyperthermia. Research on fever therapy for cancer has been performed in medical schools and research centers since the 1980s. These studies have been conducted primarily in the U.S., Germany, and Japan, but also in Australia, China, Denmark, Italy, the Netherlands, New Zealand, Norway, South Korea, and other countries. American research has been conducted in FDA-approved studies at centers such as the Mayo Clinic, University of Pennsylvania, University of Texas, and Duke University. These studies reflect a global dialogue between researchers across the world that has systematically defined effective fever therapy.
At the Medical Center Cologne, total-body hyperthermia is given to approximately 70 % of all patients. Because fever is a stress to the system, it is usually not given to patients who have severe cardiac decompensation or patients with brain cancer because it potentially can evoke cardiac difficulties or an epileptic seizure. For almost all other patients, total-body hyperthermia has no negative side effects, or risks. Usually when patients complete the fever-range, total-body hyperthermia treatment, they feel cleansed and energized. In many cases, this hyperthermia treatment is provided first in the protocol to simulate the fever response of the body.
To personally understand and experience the nature of fever-range, total-body hyperthermia, Erik Peper , PhD, volunteered to experience a treatment.
When I arrived at the clinic for my hyperthermia treatment, the nurse checked me in and then helped me settle into the hyperthermia chamber, which is essentially a light box heated by infra-red lighting.
My head was outside the box, comfortably supported by a pillow, which avoids any sense of claustrophobia. The doctor then began an IV infusion of electrolyte minerals to assure that I would not get dehydrated. The infusion included antioxidants, particularly vitamin C and selenium. An electronic thermometer was provided rectally so that my core temperature could be monitored continuously. To monitor my heart rate during the treatment, the nurse also placed a few electrodes on my skin, attached with gel. (This is another step provided to assure the safety of all patients.)
The lights inside the light chamber gradually increased my temperature. However, because the container is relatively air-tight, perspiration did not cool my body, which was also covered with heavy towels to retain the heat. My temperature gradually increased. After about three hours, the lights were turned off, but my temperature continued to increase for a while because the blood just under the surface of my skin was still warmer than the rest of my body. Once my skin began to cool, the returning blood began to cool and my core temperature very slowly began dropping naturally. For me, the worst side effect of hyperthermia treatment was boredom and the inability to turn over while lying on my back for four and a half hours. My major concern occurred about 2 hours into the treatment, I had to urinate. This was solved by urinating into a special container. When the treatment session was finished, I took a shower, shampooed my hair, and felt
comfortably warm, very relaxed, and ready for a meal. I went downstairs to the hospital cafeteria and ate a large salad and a delicious dessert. This is a very different experience than I imagine I would have had with chemotherapy or radiation.

Erik Peper, PhD

Hyperthermia can be used as the primary form of treatment or safely applied in combination with conventional therapies such as chemotherapy or radiation. Controlled studies have documented that chemotherapy or radiation in combination with total body hyperthermia becomes more effective, often with fewer side effects than chemotherapy or radiation alone. In the European Union, this combination therapy is widely available at numerous major cancer treatment centers in cities such as Amsterdam, Hamburg, Munich, Rotterdam, Stuttgart, and Utrecht.

The Process of Fever Therapy

The goal of hyperthermia in oncology is to induce a fever state that will activate the immune system, and destroy the cancer cells. The patient lies within a hyperthermia chamber where their body is heated by a especially developed infrared lamps, the safest, most natural source of warmth currently available. Infrared waves are invisible light waves close to those of visible light on the spectrum.
In nature, the sun is the most effective source of infrared radiation, supporting all life processes on earth. In hyperthermia, short-wave infrared radiation penetrates the skin and warms blood vessels close to the surface of the skin. As the temperature rises in the skin and the blood flowing through the skin, the warmth spreads throughout the body, and core temperature begins to increase. Infrared light is one of the primary means used to heat the body in total-body hyperthermia.
As the heat is gradually increased, the patient begins to perspire but without airflow, evaporation cannot occur. Transpiration and perspiration only lead to cooling if the water can be evaporated. Perspiration is our primary means of maintaining stable body temperature. Without this process, body temperature continues to increase, raising core temperature, and inducing a fever-like state. Once the fever is reached and maintained for one to two hours, the heat is very gradually reduced over the course of another hour or two.
In the Gorter Model, directly after total-body hyperthermia treatment, patients receive an injection of dendritic cells cultured from their own blood. They usually experience mild flu-like symptoms for 6 to 12 hours right after the treatment. This is not the flu—it is the body’s response, which indicates that the immune system is being activated.
After these symptoms subside, almost all patients report less pain, and a sense of well-being. It has been observed that patients who react with flu-like symptoms after the vaccination with dendritic cells do clearly better and show more benefit from the therapy than those patients who cannot amount any flu-like symptoms at all. All patients who went in complete remission always experienced flu-like symptoms.

How Fever Activates the Immune System

The core body temperature of a human being is approximately 98.6° F (37° C) and varies during the day. In total body hyperthermia, the patient’s core body temperature is slowly increased to about 102.2° F (39° C) and sometimes even higher to 104° F (40.0° C) if it is medical appropriate.
The immune shift is triggered by an impulse from deep within the brain stem in the hypothalamus. This area of the brain contains the command center for our most basic functions, especially those our bodies carry on without our conscious awareness such as breathing, blood pressure, and core body temperature.
This command center guides the autonomic nervous system, which functions “automatically.” Fever is triggered from deep within the most ancient area of the brain, also present in all mammals, which demonstrates how fundamental fever is to our functioning.
Total-body hyperthermia treatment is used to re-launch and activate cells of the immune system. These defenses increase targeted efforts to destroy the cancer through cytotoxicity. This selective toxicity by immune cells targets malignant cells, resulting in tumor cell death (necrosis and apoptosis). Healing occurs as the cancer load is lowered through improved immune activity. In sum, the fever primes the immune system to destroy cancerous cells and triggers increased immune responses throughout the whole body.
I was diagnosed with colon cancer and that spread to my liver. Although I did well on the chemotherapy, the oncologist made it clear that treatment was palliative and not a cure. So we made an appointment for a consultation in Cologne. When we learned that Dr. Gorter’s treatment could be used together with chemotherapy, we decided to do that as well.
I began the total body hyperthermia and dendritic cell therapy in Cologne. Once you’ve received the treatment, you know what to expect. It’s not painful and I was hardly sick at all. I usually feel worse after the dendritic cell vaccination, but only for one day. Every nine weeks a scan is made and they show that there are no new tumors and the liver tumors are getting smaller. The fact that my cancer has stabilized is remarkable.

(Truus Kleij-Swan, more than five year long-term survivor of intestinal cancer, metastasized to the liver, lymph nodes and peritoneum.)

Safety and Effectiveness of Hyperthermia

The approach to fever-range whole-body hyperthermia in the Gorter Model is based on 25 years of clinical experience by Robert Gorter, MD, PhD. The model differs from other treatment protocol in several ways.
Comprehensive therapy—At the Medical Center Cologne, total-body hyperthermia is usually provided in combination with local hyperthermia, injections of dendritic cells, mistletoe injections, and IV nutrients for immune restoration. This therapy enables the immune system to better identify cancer cells and targets efforts to destroy them.
Low intensity—Controlled fever is maintained at a moderate temperature to safe-guard the well-being of the patient. Maximum temperatures range from 101.3 F (38.5 C) to 103 F (39.5 C).
Carefully-staged treatment—Temperature is gradually increased for three hours and then, after a plateau of about one hour, allowed to return to normal over the course of one to two hours. The average treatment lasts four to six hours in total.
Optimal timing—Hyperthermia in combination with dendritic cell vaccinations is provided six times monthly. A major difference with other hyperthermia protocols is the timing sequence. Namely the induced total-body hyperthermia mobilizes the immune system and then the immune system is augmented by the dendritic cell vaccinations. Thus, the body receives millions of its own activated dendritic cells, timed to work together with fever-induced immune system activation.
An absence of side effects—This process involves the body’s innate immune responses, Treatment is accomplished with almost no disruption or side effects—typically less than one day of mild flu-like symptoms at most.
Primary therapy—This timed approach is almost always effective in restarting and enhancing immune function and competence. This method harnesses the biological healing power of fever in the treatment of cancer patients. 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, improved health, and healing, even in many patients with Stage III and IV (end-stage) cancer.
Complementary to conventional treatment—Fever-range total-body hyperthermia can be applied as part of a comprehensive immune therapy program or in combination with conventional therapy such as chemotherapy or radiation. The majority of studies have focused on this combination treatment. Research has shown that hyperthermia increases the effectiveness of conventional therapy with fewer side effects than chemotherapy or radiation treatment alone. Also, conventional therapies sustain their efficacy when given in combination with hyperthermia. In the European Union, this type of combination therapy is widely applied in most major cancer treatment centers.

Total Body Hyperthermia Research and Clinical Trials

Induced total-body hyperthermia was first studied in animal models 25 years ago, and then in humans over the past 20 years, both in cancer patients and in healthy volunteers. Initial studies explored the most effective ways to administer the therapy, defining the length of treatment, heat sources, optimal temperatures, and the effects produced.
Treatment has been applied as a free-standing therapy, in combination with immune therapies such as dendritic cell injections, and with conventional therapies such as radiation, chemotherapy, or hormones. Decades of research have shown that hyperthermia is a safe procedure for the greater majority of patients and many types of cancer.i ii
Effectiveness—Natural killer (NK) cells play an important in destroying the cancer cells. Hyperthermia is effective in recruiting natural killer cells into action. When dendritic cells are also provided through inoculation, they activate toxic (cytotoxic) T-cells, alerting them to the cancer tissue in the body. Working in combination, these immune cells have inhibiting effects on tumor growth.
Safety and duration—Studies conducted in the 1980s and 1990s established hyperthermia as a safe form of treatment.i ii Studies in Germany have also confirmed the safety of infrared radiation as an optimal heat source. This is the form of heat used at the Medical Center Cologne in total-body hyperthermia. In terms of the length of the therapy, early studies provided hyperthermia for a duration of 30 to 60 minutes, but most treatment provided today is typically two to four hours, depending on the patient’s response, plus a cooling down period of one to two hours.
The Cologne model utilizes a protocol of at least 3 to four hours in which the temperature is gradually increased over the course of 120 minutes or longer, followed by a 60-minute interval when the temperature is maintained at a steady level (plateau) before cooling to restore normal temperature.

Modulating core temperature—Research has confirmed that traditional forms of heat therapy such as mineral baths and Jacuzzis have very limited effect on core temperature. A study at the Medical University of Hannover, Germany showed that when body temperature was raised via warm baths which were gradually heated to 42 C (approx 107 F), core temperature actually increased less than one degree Fahrenheit (or 0.4 C) above normal.vi
Activating the immune system—It is well recognized that the immune system ramps up and doubles the level of immune activity in the blood at 101.3 F C (38.5). Therefore the maximum temperature used with patients at Cologne is 102.2 F (39 C). This moderate approach to hyperthermia increases the safety factor, while effectively promoting an immune response. Research from the University of Vienna has shown that in a test tube evaluation, when the blood was heated to 102.2 F (39 C), the level of protective monocytes multiplied by 10 times. These researchers also confirmed that one of the mechanisms that promote this increase is heat shock proteins, a factor in the blood that plays a role in calling up the immune response.
Tapping the body’s intelligence—A study in Hamburg, Germany found that an increase in body temperature alone does not automatically induce the immune response. In this research, 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 temperatures. Although participants in both groups experienced elevated temperatures, immune function increased in the cancer patients, but not in the healthy volunteers. Elevated immune factors in the cancer patients included human growth hormone, and the induction of natural killer cells, and T-cells.iv
Moderating temperature—In contrast to the Gorter Model, many of the research studies use temperatures in the range of 41.8 to 42 C (107.5 F) and in some of studies patients were anesthetized so they could tolerate these high temperatures. (Unnecessary anesthesia is always to be avoided, since it can induce senility in older patients, in a phenomenon known as Sundowner Syndrome and general anesthesia in general is often immune suppressing.)
Treatment without side effects—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.” The study showed 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.
Minimizing distress—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.”iii However, patients with a history of heart disease or brain tumors must be carefully screened. At Cologne only 70% of patients are considered eligible for hyperthermia. Additional safety measures used in Cologne include an electrolyte IV solution to avoid dehydration and monitoring of the heart rate at all times.
Therapeutic fever in combination with conventional therapies—Hyperthermia has also been found to increase the successful use of radiationviii and chemotherapyix and does not interfere with the activity of medication (17). A study conducted at a medical center in the Netherlands tracked the progress of 378 cancer patients receiving hyperthermia and also radiation treatments. Over an 8-year time period, a positive response was achieved in 77% of patients. At 5 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.”xvi
In the majority of studies, a stabilizing therapeutic response was experienced by more than 50% of patients—typically 56% to 80% of those treated. Hyperthermia is becoming accepted throughout Europe and has been researched in the U.S. at university medical centers such as the University of Pennsylvaniavii and the University of Texasix. We predict that the next phase of this research will focus on hyperthermia as a freestanding cancer therapy for patients with inoperable tumors and those who require or desire a protocol low in toxicity.

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