By Matti Narkia, Helsinki, Finland
Introduction
Fever therapy, which has helped to stop or slow down the advancement of my disease is an American invention, which in the latter part of this century has mainly been practised in Europe. Because of recent inquiries, and to pay tribute to the great American doctor who invented this therapy, I did some homework and collected information about fever therapy from the books of three American authors into a concise summary. The information includes data up to 1991, I have no knowledge of what, if anything, has happened in this area since then.
I have included contact information of some clinics which include fever therapy in their cancer program. Some of this data may have changed. I obtained this information from the books mentioned, I have no knowledge of the quality of the medical services offered and therefore cannot endorse any of them. If you have any further information - positive or (especially) negative - of the quality of the services, success rate etc.., of these clinics, I would greatly appreciate it if you mailed me a comment.
Coley's Toxins a.k.a. Mixed Bacterial Vaccine (MBV)
History
In 1888, Dr. William B. Coley (1862-1936), Harvard Medical School graduate, and eminent New York City surgeon and Sloan-Kettering researcher, stumbled across one of the most intriguing findings ever made in cancer research. In fact, his invention was a starting point for all modern immunotherapy. His discovery was first tolerated, then ridiculed, and finally suppressed, although in recent years some new interest in his discovery has emerged among researchers.
Frustrated after losing his first patient at Memorial Hospital, a 19 year old female bone cancer patient, despite an early detection followed by prompt amputation of her arm and a good prognosis, Coley began methodically searching the patient records at New York Hospital . He went back 15 years and examined records of all bone cancer patients. Most cases ended in failure and death. To his amazament, however, Coley discovered one patient who had been given up for lost by his doctors and yet had walked out of the hospital in apparently perfect health [1]. On his deathbed, this patient had suffered two attacks of erysipelas, a severe skin infection caused by bacteria Streptococcus pyogenes.
Coley's first attempts to produce reaction in cancer patients by injecting streptococcus cultures into them ended in failure. Luckily, he managed to get a particularly virulent culture from a famous German bacteriologist, Robert Koch, through a friend. The patient who received this culture developed a severe case of erysipelas with high fever. Within a few days the tumors on his tonsils and neck completely disappeared. In 1893 Coley published his first paper on the new method [2].
Because using live bacteria was dangerous and caused an ordeal for the patient, Coley later tried to and succeeded in improving his method. Instead of using bacteria, he mixed the toxins of the strep with those of another germ, Bacillus prodigiosus, which today is called Serratia marcesens. This seemed to work similarly to the live culture.
Best results were obtained when Dr. Coley or his colleague supervised the production of toxins. Parke-Davis, the pharmaceutical company, also produced the toxins commercially for many years, but they heated the formula, which reduced its effectiviness. Despite that, even this weakened form of toxins, Parke-Davis formula #IX, showed 37 percent cure rate for inoperable patients.
In 1943 NCI researcher M.J. Shears discovered that the biologically active substance in Coley's toxins is lipopolysaccharide (LPS), which occurs in the cell walls of gram-negative bacteria [4].
By 1953, however, all the production of the toxins in the United States stopped.
For over 30 years starting late 50s or early 60s, Dr. France Havas, professor emeritus of the Department of Microbiology and Immunology at Temple University School of Medicine, Philadelphia, studied the effects of Coley's toxins in mice and humans. The results of her studies were generally favorable, even in advanced patients [5,6,7,8].
In 1976 randomized trials of mixed bacterial vaccines (MBV) - as Coley's toxins are now called - begun at Memorial Sloan-Kettering.
In 1991 K.F.Kolmel and colleagues in Gottingen, Germany reported on favorable results obtained on treatment of advanced melanoma with Coley's toxins [9].
Recently Coley's toxins have been researched and used also in China. Zhao and others published 1991 preliminary results of these trials [10].
Proof
Coley's results have been tabulated by his daughter, Helen Coley Nauts, D.Sc., former executive director of the Cancer Research Institute, Inc., in New York City [11]. She and her medical colleagues have documented 894 cases treated with Coley's vaccine. Examples:
Tumor type # of operable Alive after # of inoper. Alive after
patients 5 years patients 5 years
Giant cell
bone tumor 38 33 (87%) 19 15 (79%)
Breast cancer 13 13 (100%) 20 13 (65%)
Other 5-year survival rates: 67% in Hodgkin's disease, 67% in inoperable ovarian cancer, 60% in inoperable malignant melanoma. Overall, patients with inoperable tumor of various kinds had 45% 5-year survival, while those with operable tumors had 50%.
In 1962, Dr. Barbara Johnston, M.D. published a double blind study on Coley's toxins. This study was conducted at New York University-Bellevue Hospital. The results were clear-cut. In the control group treated with fever inducing placebo, only one patient of 37 showed any signs of improvement. Of the 34 patients treated with Coley's toxins, 18 showed no improvement, 7 noted decreased pain while 9 showed such benefits as tumor necrosis, apparent inhibition of metastases, shrinkage of lymph nodes, and disappearance of tumors [12].
In 1982 at the conference held in Cologne, Germany, Mrs. Nauts reported the first results of randomized trials of MBV (Coley's toxins) begun in 1976 at Memorial Sloan-Kettering: Advanced non-Hodgkin's lymphoma patients receiving MBV had a 93 percent remission rate as opposed to 29 percent for controls who received chemotherapy alone [13].
References
[1] Cancer Research Institute. Review of Progress and Hope. New York 1976.
[2] Coley, William B. "A Preliminary Note on the Treatment of Inoperable Sarcoma by the Toxic Product of Erysipelas." Post-graduate 8:278-86, 1893.
[3] Coley, William B. "The Cancer Symposium at Lake Mohonk." American Journal of Surgery (New Series) 1:222-25, October 1926.
[4] Ward, Patricia Spain. Memo to John Gibbons. December 2 1988.
[5] Havas H, et al. Mixed bacterial toxins in the treatment of tumors. I. Methods of preparation and effects on normal or Sarcoma 37-bearing mice. Cancer Res. 1958;18:141-148.
[6] Havas H, et al. Mixed bacterial toxins in the treatment of tumors. III. Effect of tumor removal on the toxicity and mortality rates in mice. Cancer Res. 1960;20:393-396
[7] Havas H, and Donnelly A. Mixed bacterial toxins in the treatment of tumors. IV. Response of methylcholanthrene-induced, spontaneous, and transplanted tumors in mice. Cancer Res. 1961;21:17-25.
[8] Havas H, et al. The effect of bacterial vaccine on tumors and immune response of ICR/Ha mice. J Biol Res Mod. 1990;9;:194-204.
[9] Kolmel K, et al. Treatment of advanced malignant melanoma by a pyrogenic bacterial lysate. A pilot study. Onkologie. 1991;14:411-417.
[10] Zhao YT, et al. Preliminary reult of mixed bacterial vaccine as adjuvant treatment of hepatocellular carcinoma. Med Oncol & Tumor Pharmacother. 1991;8:23-28.
[11] Nauts, Helen Coley. Immunotherapy of Cancer by Bacterial Vaccines. Paper read at International Symposium on Detection and Prevention of Cancer. New York, April 25 - May 1, 1976.
[12] Johnston, Barbara, "Clinical Effects of Coley's Toxin. 1. Controlled Study. 2. A Seven-Year Study." Cancer Chemotherapy Reports 21:19-68, August 1962.
[13] Nauts, Helen Coley, Bacterial Products in the Treatment of Cancer: Past, Present and Future. Paper read at the International Colloqium on Bacteriology and Cancer, Clogne, Federal Republic of Germany, March 16-18, 1982.
[14] Nauts, Helen Coley, Bacterial vaccine therapy of cancer. Dev Biol Stand. 1977;38487-94.
[15] Nauts, Helen Coley, Bacterial pyrogens: bemeficial effect on cancer patients. Prog Clin Biol Res. 1982;107:687-96.
[16] Nauts, Helen Cole, Bacteraia and cancer - antagonisms and benefits, Cancer Surv. 1989;8:713-23.
[17] Keen AR and Frelick RW, Response of tumors to thermodynamic stimulation of the immune system. Del Med J. 1990;62:1115-6.
[18] Cunningham RS and Pearson FC. ImuVert activation of natural killer cytotoxicity and interferon gamma production via CD16 triggering. Int J Immunopharmacol. 1990;12:589-98.
[19] Jimenez JJ et al. Treatment with ImuVert aborts development of chloroleukemia in newborn rats. J Biol Response Mod. 1990;9:300-4.
[20] Cress NB, et al. ImuVert therapy in the treatment of recurrent malignant astrocytomas: nursing implications. J Neorosci. Nurs. 1991;23:29-33.
[21] Jaeckle KA, et al. Phase II trial of Serratia marcesenses extract in recurrent malignant astrocytoma. J Clin Oncol. 1990;8:1408-18.
[22] Abe H. [antitumor effect of LPS immobilized beads]. Nippon Geka Gakkai Zasshi. 1991;92:627-35.
Resources
In USA:
For treatment contact Waisbren Clinic:
Burton A. Waisbren Sr., MD, FACP
2315 North Lake Drive
Room 815, Seton Tower
Milwaukee, Wisconsin 53211
Phone: 414-272-1929
For information contact:
Cancer Research Institute
681 Fifth Avenue
New York, NY 10022
Phone: 800-223-7874, in New York 800-522-5022
In Germany:
Klaus F. Kolmel, Priv. Doz. Med.
Universitats-Haup Klinik
von Sieboldstrasse 3
3400 Gottingen, Germany
Phone: +49-551-396-081. Fax: +49-551-396-092
In China:
Coley Hospital
Phone: +86-1-868-401. Dr. Guo Zheren, MD.
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