Hydrazine Sulfate: Is It an Anticancer
Saul Green, Ph.D.
Cachexia is the result of a complex array of metabolic abnormalities which results in loss of
appetite, tissue wasting, muscle and visceral organ atrophy, weakness, and loss of fat stores. It may be accompanied by energy,
anemia, lowered serum albumin, lowered immune function, lactic acidosis, hyperlipidemia, glucose intolerance and increased
gluconeogenesis. These abnormalities alert clinicians to the possibility of an underlying disease.
The relationship between cachexia and cancer has been known for some time.  Although cachexia
is not a universal feature in cancer, it occurs frequently in lung, pancreatic, and gastric cancer. As a consequence it has
been suggested that cachexia may contribute to death. [2,3]
The awareness among oncologists of demonstrable differences between cachexia and starvation
prompted many researchers to investigate the mechanisms underlying cachexia in the hope of reversing it. Cachexia is the result
of a complex interaction between the growing tumor and the host; when the entire tumor is removed, normal metabolism and weight
Gluconeogenesis is the production of glucose from molecules which may not be sugars. This synthesis
of new glucose takes place in tissues like liver and kidney when a high-energy compound named phosphoenolpyruvate (PEP) is
synthesized by the enzyme PEPCK present in mitochondria.
Enter Hydrazine Sulfate
Hydrazine sulfate (HS) is an inexpensive common chemical which is commercially available for
about 11 cents per gram. HS is used in the refining of rare metals, in analytical blood tests, and as an antioxidant in soldering
flux. HS is carcinogenic. It induces a range of in vitro genotoxic effects including DNA and gene damage in mammalian cells
and bacteria, and chromosomal aberrations in mammalian cells.  In 1968, HS was shown to induce lung adenomas, adenocarcinomas
and liver cell carcinomas in male rats.  HS is either genotoxic or a nongenotoxic carcinogen, i.e., it acts as a tumor
promoter for preexisting initiated cells. 
HS produces hypoglycemia in dogs and rabbits.  In 1966, Brown et al reported that HS caused
genetic mutations in normal cells and cautioned that if it was used in animals over the long term, HS should he considered
potentially carcinogenic. 
Joseph Gold, MD, is a general practitioner and the director of the Syracuse Cancer Research
Institute. 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 he deprived of the energy needed to grow. 
In 1966 P. D. Ray first published the results of his studies on the effect of L-tryptophane
and HS on the formation of phosphoenolpyruvate in the gluconeogenesis in rat liver.  Later he reported effects of various
hypoglycemia-inducing agents on carbohydrate metabolism in rats.  While HS did not react directly with PEP, it did inhibit
the conversion of oxaloacetate to PEP, the high-energy compound considered essential for the synthesis of glucose by gluconeogenesis
in liver and kidney tissue. He found that the enzyme phosphoenolpyruvate carboxykinase (PEPCK) which controlled new glucose
formation in liver and kidney tissues was inhibited by HS.
When Gold learned of these results, he concluded HS was the means to reverse cachexia. He suggested
that by feeding HS to cancer patients one could block gluconeogenesis without blocking normal energy metabolism, thus overcoming
cachexia and reversing cachexia-dependent tumor progression.
In 1971 Gold reported that HS inhibited the growth of an experimental W-256 tumor in rats. 
In 1973 he reported HS inhibited PEPCK and growth of the tumors Walker 256, B-16 Melanoma, M-S Lymphosarcoma, and L1210 Leukemia
in rats.  In 1974 he studied the relationship between PEPCK inhibition and the ability of several known gluconeogenesis
inhibitors to affect the growth of tumor cells in tissue culture. He reported that HS was not toxic for these cells. 
In 1975 Gold reported that HS potentiated standard chemotherapeutic agents like cytoxan, mitomycin, methotrexate, and bleomycin,
in rats and mice.  In 1975 he published results of an IND clinical trial in which he treated 84 terminal cancer patients
with HS. The trial lasted one year and was not randomized, double blinded, or placebo controlled. The results were: subjective
improvement, with three-quarters of subjects saying that they had better appetite, weight gain, and a general feeling of "well
being." These effects varied widely in terms of their duration, lasting from a few days to several months. The cancer in 14/84
of the patients "stabilized." (There was no mention of the growth of tumors in the rest of the patient group.) There were
no significant toxic effects due to HS. No attempt was made to monitor the ability of the HS to influence glucose metabolism
of the patients. There were no long-term follow up studies. 
There followed several randomized, double blinded, placebo-controlled clinical trials: Ochoa
et al in 1975,  H. J. Lerner,  S. B. Strum et al.,  and E. Spremulli et al.  All found HS treatment to be
of no value in reducing tumor size or in increasing patient survival time. By 1980, Regelson had treated 66 advanced-stage
cancer patients and examined them for subjective and objective responses as Gold had done.  None of Regelson's patients
had objective tumor responses that could he attributed to the HS treatment. There were brief subjective responses but they
were no different from what could have been attributed to placebo effect. HS had no effect on survival. In 1982 Gold disputed
the conclusions of Regelson and Ochoa, saying their conclusions were based on "politics" and were the result of an Establishment
conspiracy to suppress a cheap and effective cure for cancer. 
A group in Russia reported results supporting Gold's thesis. [23-25] The effects were the same
subjective effects that Gold reported, i.e., a lessening of pain, fever, hemoptysis, and an increased appetite. Filov reported
that HS produced a marked psychotropic effect in patients which occurred 23 weeks after the start of the HS administration.
Filov described it as a marked "euphoria" and stated that cachectic terminal intestinal cancer patients were unable to recognize
the reality of their conditions.
In 1984 and 1987 R. T. Cheblowski [26,27] confirmed that both a decrease in glucose tolerance
and an increase in the rate of total glucose production were seen in patients with cachexia. HS treatment for one month resulted
in improvement in abnormal glucose metabolism, weight gain, and increased appetite in some patients.
In 1990 Cheblowski examined the influence of HS on the nutritional status and survival in 65
patients with non-small- cell lung cancer.  The trials were randomized, double blinded, and placebo controlled. There
was no significant difference between HS and placebo groups with respect to progress of the cancer or survival rate of the
patients. The HS treated group did show increased appetite and some weight gain. Again HS seemed to induce a state of euphoria
in patients which caused them to believe that they were being cured. Because of modest neurotoxicity of HS, Cheblowski felt
that it would not be a good candidate for use in long-term treatment until appropriate trials for safety were run. Cheblowski
concluded, "Considering all patients, survival was slightly greater for the HS treated group compared with the placebo group,
but the differences did not achieve statistical significance." More studies with better trial design need to be done.
In June 1994, three papers [29-31] described the effects of adding HS to the chemotherapeutic
regimens of patients with advanced non-small-cell lung cancer and leukemia, advanced colorectal cancer, and with newly diagnosed
non-small-cell lung cancer. All three placebo-controlled double-blinded clinical trials yielded results leading authors to
conclude: "This study demonstrates that there is no benefit from the addition of HS to an effective cytotoxic regimen."
A Media Assessment
In July 1994 Penthouse magazine carried a story by Jeff Kamen that proclaimed to its readership,
"The Russians are benefiting from Dr. Gold's cancer drug, a drug our own government seems determined to destroy." Kamen, a
freelance writer, not a medical research scientist, came to this conclusion after an all-expense paid visit to the N.N. Petrov
Research Institute of Oncology in St. Petersburg, Russia, where Gershanovich and Filov, two long-time proponents of HS use
in cancer, worked. The Russians told Kamen that they had treated 1000 cancer patients with HS and cured them. Since Kamen
believed them, he concluded that the truth about HS had been suppressed in the United States by the NCI and FDA.
In this same article, Kamen cited the testimonial of one Dr. Joanne Daniloff, Department of
Veterinary Medicine of the Louisiana State University in Baton Rouge, LA. She is quoted as saying that after the surgical
removal of most of her tumor (a glioblastoma multiforme Grade IV), her local physician told her that her cancer was incurable
She took HS, and the tumor has not returned. Dr. Daniloff is quoted as saying, "I have read studies that show clear evidence
of HS as a chemotherapeutic agent. HS alone has been shown to reduce the size of numerous tumors." Since Daniloff gave no
references for these statements, a Medline search was done for the period 1980-1990. No publications were found that offer
that evidence. A call was placed to the Department of Veterinary Medicine on January 2, 1997, to personally request those
references from Dr. Daniloff. The personnel department and the secretary of the Department of Veterinary Medicine both stated
they had no record of such a person on their staff.
Kamen ended his article by announcing that as a result of pressure from Congress, the GAO agreed
to investigate the NCI's conduct regarding clinical trials cited above. In September 1995 the GAO concluded that the three
large randomized, placebo-controlled clinical trials that were sponsored by NCI were correctly done and that the conclusion
that HS was ineffective in extending survival in cancer patients were also valid.
In 1996 British medical scientists published two extensive reviews on the subject of cancer
In December 2000, the Annals of Internal Medicine published a case report of a 55-year-old
man with cancer of the sinus near his left cheekbone. Instead of undergoing recommended medical treatment, he obtained hydrazine
sulfate through a Web site and, for four months, followed the regimen published on the kathykeeton.com Web site. Two weeks
later, he was hospitalized with signs of kidney and liver failure. Despite intensive hospital care, he died within a week
Summary and Conclusions
My review of all the literature (including Gold's) on the subject of the efficacy of hydrazine
- HS has never been shown to act as an anticancer agent
- Patients do not experience remissions or regressions of their cancer
due to HS treatment
- Patients treated with HS do not live longer than nontreated 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.
- HS is not risk-free.
For Additional Information
- Rohdenherg GL. JAMA. 1919;72: 1528-1529.
- Warren S. Am J Med Sci. 1932; 185: 610-615.
- Fearon KCH. Ann Surg. 1988; 208: 1 -5.
- DeSerres F] et al. Evaluation of Short Tests for Carcinogenesis. Oxford,
UK Elsevier/North Holland; 1981: 77-85.
- Sever L. J Natl Cancer Inst. 1968; 41: 331-349.
- Douglas GR et al. Carcinogenesis. 1995; 16: 801-804.
- Underhill FP. J Biol Chem. 1911; 10: 159.
- Brown et al. Biochem Biophys Res Comm. 1966; 24: 967. 14. 15.
- Gold J. Oncology. 1968; 22: 185.
- Ray PD.J Biol Chem. 1966; 241: 3904-3908.
- Ray PD.J Biol Chem. 1970; 245: 690-696.
- Gold J. Oncology. 1971; 25: 66-71.
- Gold J. Oncology. 1973; 27: 69 8013.
- Gold J. Oncology . 1974; 29: 74-89.
- Gold J. Oncology. 1975; 31: 44.
- Gold J. Use of hydrazine sulfate in terminal and preterminal cancer patients: results of investigational
new drug (IND) study in 84 evaluable patients. Oncology 32 1-10, 1975.
- Ochoa et al. Cancer Chemotherapy Reports. 1975; 59:1151-1154.
- Lerner HJ. Cancer Treat Rep. 1976; 60:959.
- Strum SB et al. Proc Amer Assn Cancer Kes. 1975; 16: 243.
- Spremulli E. et al. Cancer Chemo Pharm. 1979; 3: 121.
- Regelson W. JAMA. 1980; 243 337.
- Gold J. Cancer Journal News. 1982; 16 (3/4).
- Gershanovich Ml et al. Cancer Treat Rep. 1976; 60: 933.
- Tret V et al. Probl Oncol. 1977; 23 94. 25.Filov VA et al. Vopr Onkol.
1990; 36 721. 26.Cheblowski RT. Cancer Research. 1984; 44: 857.
- Cheblowski RT. Cancer. 1987; 59: 406.
- Cheblowski RT. Hydrazine sulfate influence on nutritional status and survival in non-small-cell lung cancer. Journal of Clinical Oncology 8:9-15, 1990.
- 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. Journal of Clinical Oncol.ogy 12:1113-1120, 1994.
- Loprinzi CL. Randomized placebo-controlled evaluation of hydrazine
sulfate in patients with advanced colorectal cancer. J Clin Oncol. 1994; 12: 1121-1125.
- Loprinzi CL. Placebo- controlled trial of hydrazine sulfate in patients
with newly diagnosed non small-cell lung cancer. J Clin Oncol. 1994; 12: 1126-1129.
- Euro J Surg Oncol. 1996; 22: 192-196,286-297.
- Hainer MI and others. Fatal hepatorenal failure associated with hydrazine sulfate. Annals of Internal Medicine 133:877-880, 2000. [PDF].
- Black M, Hussain H. Hydrazine, cancer, the internet, isoniazid, and the liver. Annals of Internal Medicine133:911-913, 2000. [PDF]
About the Author
Dr. Green is a biochemist who did cancer research at Memorial Sloan-Kettering Cancer Center
for 23 years. He consults on scientific methodology and has a special interest in unproven methods. He can be reached at (212)