NOTE: The information in this summary is no longer being updated and is provided for reference purposes only.
This cancer information summary provides an overview of the use of hydrazine sulfate as a treatment for people with cancer. The summary includes a brief history of hydrazine sulfate research, results of clinical trials, and possible side effects of hydrazine sulfate use.
This summary contains the following key information:
Many of the medical and scientific terms used in the summary are hypertext linked (at first use in each section) to the NCI Dictionary of Cancer Terms, which is oriented toward nonexperts. When a linked term is clicked, a definition will appear in a separate window.
Reference citations in some PDQ cancer information summaries may include links to external websites that are operated by individuals or organizations for the purpose of marketing or advocating the use of specific treatments or products. These reference citations are included for informational purposes only. Their inclusion should not be viewed as an endorsement of the content of the websites, or of any treatment or product, by the PDQ Integrative, Alternative, and Complementary Therapies Editorial Board or the National Cancer Institute.
Hydrazine sulfate has been investigated as an anticancer treatment for more than 30 years. It has been studied in combination with established treatments as a chemotherapy agent. It has also been studied as a treatment for cancer-related anorexia (loss of appetite) and cachexia (loss of muscle mass and body weight). Similar to other hydrazine compounds, it has a core chemical structure that consists of two nitrogen atoms and four hydrogen atoms.
Hydrazine sulfate is marketed in the United States as a dietary supplement /nutraceutical by some companies. In the United States, dietary supplements are regulated as foods, not drugs. Therefore, premarket evaluation and approval by the U.S. Food and Drug Administration (FDA) are not required unless specific disease prevention or treatment claims are made. The FDA can, however, remove from the market dietary supplements that it deems unsafe. The use of hydrazine sulfate as an anticancer treatment outside of clinical trials has not been approved by the FDA. The FDA has not approved the use of hydrazine sulfate for any medical condition.
To conduct clinical drug research in the United States, researchers must file an Investigational New Drug (IND) application with the FDA. The FDA has granted IND status to at least three groups of researchers to study hydrazine sulfate as a treatment for cancer.[
In animal studies, hydrazine sulfate has been added to the drinking water or the food supply, or it has been given by injection. In clinical trials involving cancer patients, hydrazine sulfate has been administered in pills or capsules.[
During the past 90 years, hydrazine compounds have been studied in animal cells grown in the laboratory, in live animals, and in humans.[
Although it was proposed in the early 1900s that hydrazine compounds are toxic to animals and to humans, they have been administered as antidepressant (e.g., iproniazid), chemotherapy (e.g., procarbazine), and antituberculosis (e.g., isoniazid) drugs. In addition to medicinal uses, hydrazine compounds have been used in industry and agriculture as components of rocket fuel, as herbicides, and as antioxidants in boiler and cooling-tower water.[
Two mechanisms of action have been proposed for hydrazine sulfate to explain its potential antitumor and anticachexia properties. Both mechanisms involve the utilization of glucose (sugar), which tumors require as a main source of energy for growth. In one proposed mechanism, hydrazine sulfate blocks gluconeogenesis through inhibition of the enzyme phosphoenolpyruvate carboxykinase.[
In the second proposed mechanism, hydrazine sulfate inhibits tumor necrosis factor (TNF)-alpha activity.[
Hydrazine compounds have been studied both as potential anticancer drugs and as cancer-causing agents. Early studies of hydrazines, including hydrazine sulfate, were conducted to determine whether these compounds could cause cancer in healthy laboratory animals.[
Animal studies of hydrazine sulfate as a treatment for cancer have investigated this compound as a single agent and in combination with established chemotherapy drugs.[
It is important to note that the best tumor responses to hydrazine sulfate as a single agent (i.e., tumor reductions of approximately 50% or more) were accompanied by substantial losses in animal body weight.[
In other experiments, hydrazine sulfate was combined with individual chemotherapy drugs (cyclophosphamide, mitomycin C, methotrexate, bleomycin, fluorouracil [5-FU], carmustine [BCNU], or neocarzinostatin) to treat Walker 256 carcinosarcoma tumors in rats and solid L-1210 leukemia tumors in mice.[
Addition of the drug clofibrate to the hydrazine sulfate plus chemotherapy drug combinations was reported to produce even greater antitumor effects.[
Hydrazine sulfate has also been tested in combination with drugs that affect the uptake of glucose by cells. The combination of hydrazine sulfate and phloretin, a drug that blocks glucose uptake, showed greater activity against FBCa bladder cancer tumors in rats than was found with hydrazine sulfate alone; however, this combination did not exhibit enhanced antitumor activity against 13762NF mammary adenocarcinomas in rats.[
In the 1980s, the National Cancer Institute (NCI) conducted preclinical studies of hydrazine sulfate as a single agent, using many of the animal tumor models described above. With the exception of borderline activity against Walker 256 carcinosarcomas in rats, no evidence of antitumor activity was found.[
Most of the information presented here is summarized in a table located at the end of this section.
Hydrazine sulfate has been studied extensively in patients with advanced cancer. These studies have evaluated the following: a) tumor response and/or survival among patients with various types of cancer,[
The first clinical tests of hydrazine sulfate as a treatment for cancer were conducted in the mid-1970s by a pharmaceutical company.[
In 1976, Russian investigators reported findings from 95 patients with advanced cancer who had been treated with hydrazine sulfate after all previous therapy (surgery, chemotherapy, and/or radiation therapy) had failed.[
In 1981, the same investigators published findings from 225 patients with advanced disease who had been treated with hydrazine sulfate after all previous therapy had failed.[
In 1995, the same Russian investigators published findings from 740 patients with advanced cancer.[
In 1994, the same investigators reported findings from a clinical series involving 46 patients with malignant brain tumors (38 with glioblastomas, four with astrocytomas, and four with meningiomas) and six patients with benign brain tumors.[
Evaluation of the findings from these Russian clinical series [
Findings from four placebo-controlled, randomized clinical trials, however, also fail to support the effectiveness of hydrazine sulfate as a cancer treatment in humans.[
One of the trials involved 65 patients with advanced non-small cell lung cancer and examined the effects of hydrazine sulfate on survival and nutritional status.[
A CALGB-sponsored trial also evaluated the use of hydrazine sulfate as a treatment for patients with advanced non-small cell lung cancer.[
The use of hydrazine sulfate as a treatment for patients with non-small cell lung cancer was also evaluated in an NCCTG-sponsored trial.[
Another NCCTG-sponsored trial tested hydrazine sulfate alone versus placebo in the treatment of 127 patients with metastatic colorectal cancer.[
Four other clinical trials did find some objective evidence of benefit with hydrazine sulfate therapy.[
A search of the PDQ clinical trials database indicates that no clinical trials of hydrazine sulfate as a therapy for cancer are being conducted at this time.
|Reference Citation(s)||Type of Study||Type of Cancer||No. of Patients: Enrolled; Treated; Controlb||Strongest Benefit Reportedc||Concurrent Therapyd||Level of Evidence Scoree|
|No. = number.|
|a See text for more details.|
|b Number of patients treated plus number of control patients may not equal number of patients enrolled; number of patients enrolled = number of patients initially recruited/considered by the researchers who conducted a study; number of patients treated = number of enrolled patients who were given the treatment being studiedAND for whom results were reported; historical control subjects are not included in number of patients enrolled.|
|c The strongest evidence reported that the treatment under study has anticancer activity or otherwise improves the well-being of cancer patients. See text and glossary for definition of terms.|
|d Surgery, chemotherapy, or radiation therapy given/allowed at the same time as hydrazine sulfate treatment.|
|e For information about levels of evidence analysis and an explanation of the level of evidence scores, see Levels of Evidence for Human Studies of Integrative, Alternative, and Complementary Therapies.|
|f This study included six additional patients with benign brain tumors.|
|g Insufficient information given to permit a level of evidence analysis.|
||Randomized clinical trial||Advanced non-small cell lung||65; 32; 33, placebo||None||Yes||1iA|
||Randomized clinical trial||Advanced non-small cell lung||291; 135; 131, placebo||None||Yes||1iA|
||Randomized clinical trial||Advanced colorectal||128; 63; 64, placebo||None||No||1iA|
||Randomized clinical trial||Advanced non-small cell lung||243; 119; 118, placebo||None||Yes||1iA|
||Nonconsecutive case series||Various advanced||25; 25; None||Slight regression of some metastatic lesions, 1 patient with melanoma||No||3iiiDiii|
||Nonconsecutive case series||Various advanced||158; 84; None||Measurable tumor regression, 7 patients||Yes||3iiiDiii|
||Nonconsecutive case series||Various advanced||763; 740; None||Complete tumor regression, 6 patients||No||3iiiDiii|
||Nonconsecutive case series||Various advanced||25; 25; None||None||No||3iiiDiii|
||Nonconsecutive case series||Various advanced||32; 29; None||None||Unknown||3iiiDiii|
||Nonconsecutive case series||Various advanced||101; 71; 30, placebo||Improved weight maintenance or gain, 41 hydrazine sulfate treated vs. 17 placebo-treated patients||Yes||3iiiDiii|
||Nonconsecutive case series||Glioblastoma, astrocytoma, or meningiomaf||465; 46; None||Improved survival, patients with glioblastoma||Yes||Noneg|
The side effects associated with hydrazine sulfate use have been mainly gastrointestinal and neurologic.[
The side effects of hydrazine sulfate have been described as mild to moderate in severity, and their incidence appears to have been low. Most side effects are reported to resolve when treatment is stopped. However, limited evidence from animal studies suggests that hydrazine sulfate is highly toxic when combined with either alcohol or barbiturates.[
Several clinical case series conducted by Russian investigators have indicated that hydrazine sulfate has marginal anticancer activity, but these results are considered inconclusive due to the lack of control groups and insufficient information provided about study methodology. Well-controlled clinical studies conducted in the United States have shown no evidence of anticancer activity. In addition, evidence concerning the effectiveness of hydrazine sulfate as a treatment for cancer-related cachexia and anorexia is inconclusive. Furthermore, hydrazine sulfate has been shown to increase the incidence of several types of tumors in animals, and it has been classified as a potential carcinogen by the National Toxicology Program of the U.S. Department of Health and Human Services. The use of hydrazine sulfate as an anticancer drug outside the context of clinical trials has not been approved by the U.S. Food and Drug Administration and, thus, cannot be recommended.
Separate levels of evidence scores are assigned to qualifying human studies on the basis of statistical strength of the study design and scientific strength of the treatment outcomes (i.e., endpoints) measured. The resulting two scores are then combined to produce an overall score. For additional information about levels of evidence analysis, refer to Levels of Evidence for Human Studies of Integrative, Alternative, and Complementary Therapies.
The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.
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Purpose of This Summary
This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the use of hydrazine sulfate in the treatment of people with cancer. It is intended as a resource to inform and assist clinicians in the care of their patients. It does not provide formal guidelines or recommendations for making health care decisions.
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Levels of Evidence
Some of the reference citations in this summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Integrative, Alternative, and Complementary Therapies Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations.
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PDQ® Integrative, Alternative, and Complementary Therapies Editorial Board. PDQ Hydrazine Sulfate. Bethesda, MD: National Cancer Institute. Updated <MM/DD/YYYY>. Available at: https://www.cancer.gov/about-cancer/treatment/cam/hp/hydrazine-sulfate-pdq. Accessed <MM/DD/YYYY>. [PMID: 26389456]
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Last Revised: 2018-08-23
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