The role of your cancer health professional is to create an environment of openness and trust, and to help in making informed decisions about alternative/ complementary therapies. Collaboration will improve the safe integration of all therapies during your experience with cancer. The "Summary" and "Professional Evaluation/ Critique" sections of this Unconventional Therapies manual are cited directly from the medical literature, and are intended to help in the objective evaluation of alternative/complementary therapies.
Summary
"A review of all the literature, including Gold's on the subject of the efficacy of hydrazine sulphate (HS) shows: (1) HS has never been shown to act as an anticancer agent; (2) patients do not experience remissions or regressions of their cancer due to HS treatment; (3) patients treated with HS do not live longer than non-treated patients. Although HS may correct abnormal carbohydrate metabolism in some cancer patients, the rationale that it acts as an anticancer agent because it deprives cancers of their energy by inhibiting formation of glucose from lactic acid (gluconeogenesis) is erroneous. HS has not been shown to be an effective anticancer agent." (Green)
"In 1994 three methodically sound studies involving a combined total of 636 cancer patients were published. Each of the three found no positive effect for hydrazine sulfate. As of this writing, hydrazine sulfate is considered a disproved and ineffective treatment for cancer." (Cassileth)
"While hydrazine (hydrazine sulfate) has received much attention, unfortunately it has been shown to be ineffective in improving the symptoms of the patient with cancer cachexia." (Gagnon)
Description/ Source/ Components
Hydrazine sulfate is also known as hydrazinium sulfate and as hydra-zonium sulfate, (H6N204S). (Merck)
"Hydrazine sulfate is usually administered orally, with food or immediately before eating. It may also be given by injection. The usual cycle of treatment is 60 mg [milligrams] 3 times daily for 30-45 days followed by a rest period of 2-6 weeks. The cycle can be repeated as many times as desired. Each 60 mg dose is available in capsule form or in 15-ml vials for injection." (Kaegi)
"The product is available legally in Canada, and physicians can obtain information about its availability by contacting the Health Protection Branch of Health Canada." (Kaegi)
History
"The principal proponent and developer of hydrazine sulfate is Dr. Joseph Gold, an American research oncologist now at the Syracuse Cancer Research Institute, a private, non-profit institute that performs cancer research, including studies of hydrazine sulfate alone or in combination with other chemotherapeutic agents." (Kaegi)
"Gold was influenced by the research of Dr. Otto Warburg, a 1931 Nobel prize winner who had proposed that an important distinguishing feature of cancer cells is their propensity to obtain energy through the anaerobic, rather than the aerobic, metabolism of glucose." (Kaegi)
"In the past, Gold has advised the use of hydrazine sulfate in patients with breast cancer, sarcomas, Hodgkin's disease and other lymphomas, and neuroblastomas. He now recommends its use for all forms of cancer." (Ontario) (Kaegi)
Hydrazine sulfate is used in gravimetric estimation of nickel, cobalt and cadmium; in the refining of rare metals; as an antioxidant in soldering flux for light metals; as a reducing agent in the analysis of minerals and slags; in separating polonium from tellurium; in tests for blood; for destroying fungi and moulds; and in the preparation of hydrazine hydrate. (Merck)
Hydrazine sulfate was also used in rocket fuel in World War II. (CA)
Proponent/ Advocate Claims
"Through a series of studies, Gold developed the idea that hydrazine sulfate could slow the weight loss and wasting away of the body, known as cachexia, that often accompanies advanced stages of cancer. He also believed that hydrazine sulfate could enhance the effectiveness of other drugs." (Cassileth)
"Hydrazine sulfate, a gluconeogenic blocking agent which interrupts the cycle of tumor energy gain-host energy loss at the enzymic level of phosphoenolpyruvate carboxykinase, has been indicated as a specific chemotherapeutic agent for cancer cachexia (weak, emaciated condition)" (Gold 1981)
"Gold postulated that a metabolic circuit existed in cancer patients that allows energy needed for tumor growth to be drawn from normal metabolic pathways. According to Gold, lactic acid from tumor glycolysis, amino acids from protein breakdown, and glycerol from fat mobilization drive gluconeogenic activity, which drains away the energy which normal anabolic processes need to produce and maintain tissue integrity. This alleged 'energy short circuit' causes cachexia in cancer. If the circuit could be broken, cachexia would be overcome and the cancer would be deprived of the energy needed to grow." (Green)
"Some studies have found that hydrazine sulfate improved appetite and increased serum albumin (a blood protein that reflects nutritional parameters) and caloric intake in lung cancer patients." (Gorter) (Smigel)
Gold reports that patients receiving hydrazine sulfate had subjective improvement and tumor regression. (Gold 1971,1973,1974)
"Gold recommends that hydrazine sulfate be used in conjunction with conventional therapeutic agents. He believes that combining these agents may result in an enhanced effect, a position for which there is some support." (Kaegi)
Gold and other supporters of hydrazine sulfate were unconvinced of the findings that suggest that the use of HS had no benefit to patients with advanced lung and colorectal cancer. "They argued that the treatment protocol used in these studies did not comply fully with the recommendation that patients receiving hydrazine sulfate strictly avoid the use of agents such as barbiturates, alcohol and benzodiazepines. (Gold believes that these substances interfere with hydrazine sulfate's effectiveness.)" (Kaegi)
Professional Evaluation/ Critique
In a recent study investigating the effects of hydrazine sulfate on both in vitro [in an artificial environment] and in vivo [in a living body] models of prostate cancer, results showed no growth inhibition. "In vivo [in a living body], hydrazine sulfate did not suppress the growth of implanted Dunning rat prostate MAT-LyLu cells [the specific tumor line that was studied]. Hydrazine sulfate does not have activity in these models of prostate cancer and may not be an appropriate therapy for patients with prostate cancer." (Kamradt)
"The double blind study by Kosty and colleagues included 291 newly diagnosed, untreated patients with non-small cell cancer of the lung randomly selected after optimal treatment with cisplatinum and etoposide to receive hydrazine sulfate or placebo. There was no evidence of increased response rate or survival difference as a result of the hydrazine, but there was evidence of a poorer quality of life in the treated group. There was no difference in the two arms of this double-blind study with regard to anorexia, weight gain, or nutritional status." (Kosty) (Spencer)
In a 1993 analysis of 272 patients with advanced non-small cell lung cancer, "investigators found no significant benefit to this therapy." (Jenks)
"Dr. Gold's standards of criteria for reporting positive levels of activity in his experimental studies with solid animal tumors did not conform to those of other investigators who could not document or reproduce these results." (CA)
Studies to evaluate the therapeutic value of hydrazine sulfate in humans were undertaken at the Memorial Sloan Kettering Cancer Center:
significant subjective improvements or objective antitumor responses were not observed in any of 29 patients treated with hydrazine sulfate
4 patients had briefly improved appetites without weight gain
1 patient experienced a transitory decrease in bone pain without parallel improvement in the roentgenograms (photographs) of the bones but with continuing elevations of the serum acid phosphatase
the rate of accumulation of ascites (fluid) decreased in one patient but prior paracenteses (surgical puncture to remove fluid) had been performed. (Ochoa)
Filov and Burova report:
"Experiments in vivo (in the living body) were made to examine the action of hydrazine sulfate on the gluconeogenesis in the liver and kidneys of rats with Zajdela's hepatoma and mice with lymphoma NK/LY. The intensity of the gluconeogenesis in the liver decreased and in the kidneys increased. These alterations did not affect blood glucose content in the test animals. The data obtained do not support the hypothesis that the mechanism of hydrazine sulfate action by an abrupt depression of the gluconeogenesis during malignant growth is the sole mechanism." (Filov)
HS seemed to induce a state of euphoria in patients, which caused them to believe that they were being cured. (Green)
"Chlebowski and Grosvenor described the abnormal glucose tolerance and increased glucose production frequently seen in cancer patients and the improvement found with hydrazine sulfate in these measurable parameters thought to be a result of the inhibition of gluconeogenesis. However, in the first of the 'randomized' studies, the control group of 30 had an addition of 40 non-randomized treated patients, a serous flaw in the design of the study." (Chlebowski) (Spencer)
"The FDA has not approved it as a cancer treatment, based on the results of FDA-approved clinical trials." (Diamond)
Toxicity/ Risks
If inappropriately high doses of hydrazine sulphate are taken, mild numbness, nausea, vomiting, drowsiness and nerve inflammation may occur. (Ontario)
Side effects may include "nausea, some pruritis, dizziness due to low blood sugar, or peripheral neuritis." (Sutherland)
The following toxic symptoms have been reported: nausea, vomiting, anorexia, abnormal sensations affecting both upper and lower extremities, impaired fine motor functions (writing), confusion, minor decrease in fasting blood sugar, elevation in the serum activity of alkaline phosphatase, elevation in the serum concentration of bilirubin, abnormal electromyograms. (Ochoa)
"Since all patients had disseminated cancer, the abnormal liver function tests cannot be definitely attributed to an effect of hydrazine sulfate." (Ochoa)
Hydrazine sulfate is known to produce excitement, lethargy, convulsions, hypotension, arrhythmias, fatty changes in the liver, hypoglycemia, weight loss and terminal changes in SGOT (serum glutamin oxaloacetic transaminase) activity. (Krop)
Hydrazine sulfate has previously shown to result in a dose-dependent induction of liver tumors in rodents. (Zheng)
"Hydrazine sulfate tested in mice showed a weak but definite activity as a lung carcinogen (cancer-causing) despite the low dose used." (Mirvish)
"Hydrazine and methylhydrazine sulfate significantly increased the incidence of lung tumors in Swiss mice." (Toth)
"He [Gold] also cautions that because hydrazine and hydrazine sulfate are monoamine oxidase inhibitors, people using hydrazine sulfate should avoid foods that are rich in tyramine (e.g., certain cheeses)." (Kaegi)
Costs
It costs approximately $30 to $40 U.S. for a one-month supply. (Ontario, 1994)
"Although the product is not expensive, its costs are not covered by public or private health insurance plans." (Kaegi)
References
CA (Anonymous). Unproven methods of cancer management: hydrazine sulfate. CA: a Cancer Journal for Clinicians 1976;26:108-110.
Cassileth BR. Alternative medicine handbook: a complete reference guide to alternative and complementary therapies. New York: W.W. Norton & Co., 1998:162-163.
Chlebowski RT, et al. The scope of nutrition intervention with cancer-related endpoints. Cancer 1994;74(suppl 91):273.
Diamond WJ, et al. An alternative medicine definitive guide to cancer. Tiburon: Future Medicine Publishing, Inc., 1997:387.
Filov VA, Burova TM. Gluconeogenesis during therapy of experimental tumors with hydrazine sulfate. Biull Eksp Biol Med 1984;97(1):73-74.
Gagnon B, Bruera E. A review of the drug treatment of cachexia associated with cancer. Drugs 1998;55:675-88.
Gold J. Inhibition of Walker 256 intramuscular carcinoma in rate by administration of hydrazine sulfate. Oncology 1971;25:66-71.
Gold J. Inhibition by hydrazine sulfate and various hydrazides, of in vivo growth of Walker 256 intramuscular carcinoma, B-16 melanoma, Murphy-Sturm lymphosarcoma and L-1210 solid leukemia. Oncology 1973;27:69-80.
Gold J. Use of hydrazine sulfate in advanced cancer patients: preliminary results. Proc Am Assoc Cancer Res and ASCO 1974;15:83.
Gold J. Anabolic profiles in late-stage cancer patients responsive to hydrazine sulfate. Nutr Cancer 1981;3:13
Gorter R. Management of anorexia-cachexia associated with cancer and HIV infection. Oncology 1991 Sept Suppl;5(9):13-17.
Green Saul. Hydrazine sulfate: is it an anticancer agent? Scientific review of alternative medicine 1997;1:19-21.
Jenks S. Hydrazine sulfate ad is "offensive." Journal of the National Cancer Institute 1993 Apr 7;85(7):528-529.
Kaegi E., on behalf of the Task Force on Alternative Therapies of the Canadian Breast Cancer Research Initiative. Unconventional therapies for cancer: 4. Hydrazine sulfate. Canadian Medical Association 1998;158:1327-1330.
Kamradt JM, Pienta KJ. The effect of hydrazine sulfate on prostate cancer growth. Oncology Reports 1998;5:919-21.
Kosty MP, et al. Cisplatin, vinblastine, and hydrazine sulfate in advanced non-small cell lung cancer: a randomized placebo-controlled, double-blind Phase III study of the cancer and leukemia group B. J Clin Oncol 1994;12:1113.
Krop S. Toxicology of hydrazine: a review. Arch Int Hyg 1954;9:199-204.
Merck Index: an encyclopedia of chemicals, drugs, and biologicals. 10th ed. Rathway, N.J. : Merck 1983;691.
Mirvish SS, Chen L, Haran-Ghera N, Berenblum I. Comparative study of lung carcinogenesis, promoting action in leukaemogenesis and initiating action in skin tumorigenesis by urethane, hydrazine and related compounds. Int J Cancer 1969;4:318-326.
Ochoa M, Witter RE, Krakoff IH. Trial of hydrazine sulfate (NSC-150014) in patients with cancer. Cancer Chem Rep 1975;59:1151-1154.
Ontario Breast Cancer Information Exchange Project. Guide to unconventional cancer therapies. 1st ed. Toronto: Ontario Breast Cancer Information Exchange Project, 1994:278-280.
Smigel K. Hydrazine sulfate used in cancer patients. Journal of the National Cancer Institute 1990 Feb 21;82(4):254.
Spencer JW, Jacobs JJ. Complementary/alternative medicine: an evidence based approach. Toronto: Mosby, 1999:151-52.
Sutherland R. Rocket fuel chemical reverses cachexia in CA patients. The Medical Post 1988 Apr 26:9.
Toth, B. Hydrazine, methylhydrazine and methylhydrazine sulfate carcinogenesis in Swiss mice. Failure of ammonium hydroxide to interfere in the development of tumors. Int J Cancer 1972;9:109-118.
Zheng H, Shank RC. Changes in methyl-sensitive restriction sites of liver DNA from hamsters chronically exposed to hydrazine sulfate. Carcinogenesis 1996;17:2711-7.
Revised February 2000