Hydrazine Sulfate (PDQ)
Complementary/Alternative Medicine

Table of Contents

Overview
General Information
History
Laboratory/Animal/Preclinical Studies
Human/Clinical Studies
Adverse Effects
Levels Of Evidence
Glossary Of Terms
References
For More Information

Overview

This complementary and alternative medicine (CAM) information summary provides an overview of the use of hydrazine sulfate as a treatment for cancer. The summary includes a brief history of hydrazine sulfate research, results of clinical trials, and possible side effects of hydrazine sulfate use. A glossary of scientific terms used in the summary appears just before the references. Terms defined in the glossary are marked in the text by hypertext links.

This summary contains the following key information:

• Hydrazine sulfate is a chemical that has been studied as an antitumor agent and as a treatment for the body wasting (i.e., cachexia) associated with advanced cancer.
• It has been claimed that hydrazine sulfate limits the ability of tumors to obtain glucose, which is a type of sugar used by cells to create energy.
• Hydrazine sulfate has been shown to increase the incidence of lung, liver, and breast tumors in laboratory animals, suggesting that it may cause cancer.
• There is only limited evidence from animal studies that hydrazine sulfate has anticancer activity.
• Hydrazine sulfate has shown no antitumor activity in randomized clinical trials, and data concerning its effectiveness in treating cancer-related cachexia are inconclusive.
• Hydrazine sulfate is marketed in the United States as a dietary supplement.

General Information

Hydrazine sulfate has been investigated as a treatment for cancer for more than 30 years. It has been studied, in combination with established treatments, as a first-line agent in cancer chemotherapy. It has also been investigated 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 consisting of two nitrogen atoms and four hydrogen atoms.

Several companies distribute hydrazine sulfate as a dietary supplement. In the United States, dietary supplements are regulated as foods not drugs. Therefore, premarket evaluation and approval by the Food and Drug Administration (FDA) are not required unless specific disease prevention or treatment claims are made. Because dietary supplements are not formally reviewed for manufacturing consistency, there may be considerable variation from lot to lot.

To conduct clinical drug research in the United States, researchers must file an Investigational New Drug (IND) application with the FDA. To date, the FDA has granted IND status to at least three groups of investigators to study hydrazine sulfate as a treatment for cancer.[1-3]

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 patients with cancer, hydrazine sulfate has been administered in pills or capsules.[reviewed in 4] In the clinical trials conducted thus far, the dose and the duration of hydrazine sulfate administration have varied.

History

During the past 90 years, hydrazine compounds have been studied in animal cells grown in the laboratory, in live animals, and in humans.[reviewed in 4] More than 400 hydrazine analogs (related compounds) have been screened for their ability to kill tumors. In 1996, a retrospective review of scientific studies in which the anticancer activity of hydrazine analogs was investigated found that 65 of 82 evaluated compounds showed some anticancer activity in xenograft models (tumor cells of one species transplanted to another species).[reviewed in 4] Seven of the 82 tested compounds showed activity against human tumor cells and were, therefore, selected for further testing in pilot studies and phase I clinical trials.[reviewed in 4] Among these seven compounds, only procarbazine (a methylhydrazine derivative; also called ibenzmethyzin or natulan) completed preliminary testing in humans. Procarbazine exhibited anticancer activity in patients with Hodgkin's disease, melanoma, and lung carcinoma, and it was ultimately used in several first-line treatment regimens in the 1960s.[5,6, reviewed in 4] In view of the initial success with procarbazine, hydrazine sulfate, which is similar in chemical composition, was investigated for anticancer activity beginning in the 1970s. During this period, investigation of hydrazine sulfate as a treatment for cancer-related cachexia was also initiated. Research on hydrazine sulfate both as a single agent and in combination with standard chemotherapy regimens continued through the mid-1990s.[1,7-11]

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.[reviewed in 12-14] Many scientists consider hydrazine sulfate and other hydrazine analogs to be cancer-causing agents, and they have expressed concern about the safety of these compounds.[4,12,14-23] In the Ninth Report on Carcinogens 2000, hydrazine and hydrazine sulfate are listed by the U.S. Department of Health and Human Services' National Toxicology Program as "reasonably anticipated to be human carcinogens."[24] When the antituberculosis drug isoniazid and hydrazine antidepressants are combined with purified DNA in the laboratory, they produce hydrogen peroxide and free radicals that can damage the DNA.[19, reviewed in 16] Hydrazine compounds have been reported to cause mutations and chromosome damage in bacteria and in plant and animal cells.[reviewed in 12]

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.[25, reviewed in 26-30] Gluconeogenesis is a process by which extra glucose (in addition to that obtained from the diet) can be formed in the liver and the kidneys from the breakdown products of sugars, lipids (fats), and proteins. It has been suggested that cachexia occurs because the body must use increasing amounts of energy and other resources, including its own protein, to meet the demand for glucose by tumors.[25, reviewed in 26-31] Blocking gluconeogenesis, and interfering with the supply of nutrients to tumors, has been proposed as one way to inhibit tumor growth and to prevent cachexia.[25, reviewed in 26-31]

In the second proposed mechanism, hydrazine sulfate inhibits tumor necrosis factor-alfa (TNF-alfa) activity.[32-35] TNF-alfa, which is also known as cachectin, is one of a number of substances normally produced by white blood cells of the body in response to infection by microorganisms and in response to other stimuli, such as tissue damage.[reviewed in 32,33,35-37] Higher than normal TNF-alfa production has been observed in white blood cells obtained from cancer patients.[reviewed in 36-38] It has been suggested that higher than normal levels of TNF-alfa can cause the anorexia, the increased energy expenditure, and the increased muscle protein breakdown seen in cancer patients.[reviewed in 32,36-38] Some of the muscle protein breakdown products would become available for gluconeogenesis. Inhibition of TNF-alfa activity might, therefore, inhibit tumor growth and prevent cachexia.

Laboratory/Animal/Preclinical Studies

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.[20-23,39-43, reviewed in 15] Substantial increases in tumor incidence were observed in most studies that used rats, mice, or hamsters.[20-23,39,41-43] Hydrazine administration was associated with increases in lung, liver, and breast tumors in rats,[21,39] increases in lung and liver tumors in mice,[20-23,42] and increases in liver tumors in hamsters.[41,43] In one study, hydrazine sulfate increased the incidence of lung tumors in both males and females of the mouse strain C3H, but reduced the incidence of breast adenocarcinomas in C3H females.[22]

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.[26,27,44-48] In studies conducted in one laboratory, hydrazine sulfate alone was found to cause dose-dependent inhibition of tumor growth in rats bearing Walker 256 carcinosarcoma or Murphy-Sturm lymphosarcoma tumors and in mice bearing B-16 melanoma tumors.[26,27,44] Hydrazine sulfate alone had no effect on solid tumors formed from L-1210 leukemia cells in mice.[27] In work performed in another laboratory, hydrazine sulfate alone inhibited the growth of FBCa bladder cancer tumors in one of two experiments in rats, but it had no effect on the growth of 13762NF mammary adenocarcinomas in rats.[47] Findings from a third laboratory demonstrated that hydrazine sulfate alone had no effect on the growth of Dunning prostate cancer tumors in rats.[48] 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.[26,27,44] This finding appears to be inconsistent with the proposed use of hydrazine sulfate as an anticachexia agent.

In other experiments, hydrazine sulfate was combined with individual chemotherapy drugs (cyclophosphamide, mitomycin C, methotrexate, bleomycin, 5-fluorouracil, carmustine (BCNU), or neocarcinostatin) to treat Walker 256 carcinosarcoma tumors in rats and solid L-1210 leukemia tumors in mice.[27,44,45] For both tumor types, enhanced anticancer effects were observed. In the experiments with L-1210 tumors, cyclophosphamide and mitomycin C were more effective when combined with hydrazine sulfate than they were when used alone.[27] As indicated previously, hydrazine sulfate alone had no effect against solid L-1210 tumors.[27]

Addition of the drug clofibrate to the hydrazine sulfate plus chemotherapy drug combinations was reported to produce even greater antitumor effects.[45] Clofibrate lowers blood lipid levels and has the potential to inhibit gluconeogenesis by limiting the availability of lipid breakdown products for the synthesis of glucose.[reviewed in 45] This three-drug treatment regimen, however, was tested against only one type of tumor (Walker 256 carcinosarcomas in rats).[45]

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.[47] When hydrazine sulfate was combined with the drug phlorizden, which is similar to phloretin, using the same two tumor models, no increase in anticancer activity was observed.[47] When hydrazine sulfate was combined with the drug phenformin, which increases glucose uptake by cells (and lowers blood glucose levels), enhanced antitumor activity against Walker 256 carcinosarcomas in rats was observed.[46]

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.[reviewed in 49] In view of these results, NCI recommended against further evaluation of hydrazine sulfate as an anticancer agent.[reviewed in 49] However, clinical investigation of this compound continued, largely because of its potential as a treatment for cancer-related anorexia and cachexia.

Human/Clinical Studies

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,[1-3,7-10,50-55] b) changes in body weight,[1-3,7-9,28,50,52-54] c) carefully measured quality of life,[7-9,56] and d) changes in nutritional or metabolic status.[1,7,11,54,55,57] Clinical studies of hydrazine sulfate have been funded by a pharmaceutical company,[3] the Russian government,[10,51,52,58] and grants from the NCI.[1,2,7-9,11,50,53,54,56] They have also been sponsored by the North Central Cancer Treatment Group (NCCTG) [8,9] and the Cancer and Leukemia Group B (CALGB).[7,56]

The first clinical tests of hydrazine sulfate as a treatment for cancer were conducted in the mid-1970s by a pharmaceutical company.[3] In an uncontrolled study of 158 patients with advanced disease, it was found that 45 of 84 evaluable patients had subjective improvements (i.e., the patients reported an increase in appetite, a decrease in weight loss, an increase in strength, or a decrease in pain) and that 14 had objective improvements (i.e., there was measurable tumor regression, stable disease, or improvement in a cancer- related disorder) in response to treatment with hydrazine sulfate. Among the patients with objective responses, two had long-term (17 and 18 months) stabilization of their disease and seven had measurable tumor regression, although the extent and duration of these regressions were not specified. Major weaknesses of this study included the absence of a control (i.e., comparison) group and the fact that 74 of the 158 initially recruited patients could not be evaluated because of poor prognosis, missing documentation, insufficient duration of treatment, and/or concurrent therapy (i.e., therapy given at the same time) with other anticancer drugs.[3]

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.[51] Three partial responses (i.e., reductions in tumor size of greater than 50% observed for a period of 4 weeks or more) and no complete responses were noted after 1 to 5 months of treatment. Tumor regressions of 50% or less and stable disease (i.e., cessation of tumor growth for a period of 1.5 to 2.0 months or more) were reported for 16 and 20 patients, respectively.

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.[52] It appears that the 225 patients described in this second report [52] included the 95 patients described in the first report.[51] Partial responses and stable disease were reported for four and 95 patients, respectively, after 1 to 6 months of treatment. No patient experienced a complete response. Subjective improvements in appetite, weight stabilization or gain, pain, fever, breathing, and/or mental outlook were reported by 147 patients.

In 1995, the same Russian investigators published findings from 740 patients with advanced cancer.[10] Once again, it appears that 225 of these 740 patients were described in the earlier reports.[51,52] Partial responses and stable disease were reported for 25 and 263 patients, respectively. Complete responses were noted for six patients. Subjective improvements in cancer-related symptoms were reported by 344 patients.

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.[58] These patients were not described in the other reports.[10,51,52] All patients in this series appear to have been treated with surgery in addition to hydrazine sulfate therapy, and at least some of the patients were also treated with radiation therapy. Complete or partial regression of neurologic symptoms (e.g., seizures, headaches, sensory and motor disorders, and hallucinations) was reported for 73% of the patients. In addition, longer than average survival was reported for most patients. Among the patients with glioblastomas, the increase in average survival time was from 6 months to more than 13 months.[58]

Evaluation of the findings from these Russian clinical series [10,51,52,58] is made difficult by the limited information provided about the patients and their treatment histories. In addition, insufficient information was given about study design and methodology. The absence of control groups; the receipt of prior or concurrent surgery, chemotherapy, and/or radiation therapy by all patients; and the reliance on subjective measures of quality of life are major study weaknesses. Therefore, it is difficult to ascribe any of the positive findings to treatment with hydrazine sulfate.

In contrast with the previously described clinical series, three NCI-funded clinical series found no complete responses or partial responses among a total of 79 patients treated with hydrazine sulfate.[2,50,53] In addition, only temporary, minor improvements in appetite, pain, and weight stabilization or gain were reported by the patients in these series. A weakness in these three clinical series was the absence of control groups.

Findings from four placebo-controlled, randomized clinical trials, however, also fail to support the effectiveness of hydrazine sulfate as a cancer treatment in humans.[1,7-9,56] In these trials, survival,[1,7-9,56] objective tumor response,[1,7,56] and carefully measured quality of life [7-9,56] were major endpoints.

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.[1] In this trial, patients received either hydrazine sulfate or placebo in addition to a multiple-drug chemotherapy regimen. When all patients were evaluated, no improvement in survival was found with hydrazine sulfate therapy. In addition, no differences were noted in objective tumor response between the hydrazine sulfate group and the placebo group. However, on the basis of caloric intake and the maintenance of serum albumin levels, the nutritional status of the patients in the hydrazine sulfate group was judged better than that of the patients in the placebo group. However, the moderate increases in body weight associated with hydrazine sulfate use did not achieve statistical significance.

A CALGB-sponsored trial also evaluated the use of hydrazine sulfate as a treatment for patients with advanced non-small cell lung cancer.[7,56] In this trial, 266 patients received either hydrazine sulfate or placebo in addition to a multiple-drug chemotherapy regimen. No differences in survival, objective tumor response, anorexia, weight gain or loss, or nutritional status were observed between the hydrazine sulfate group and the placebo group. However, the quality of life of the patients who received hydrazine sulfate was found to be statistically significantly worse than that of the patients who received placebo.

The use of hydrazine sulfate as a treatment for patients with non-small cell lung cancer was also evaluated in an NCCTG-sponsored trial.[9] In this trial, 243 patients were randomly assigned to receive either hydrazine sulfate or placebo in addition to a multiple-drug chemotherapy regimen. No statistically significant differences were found between the hydrazine sulfate group and the placebo group with respect to either survival or quality of life.

Another NCCTG-sponsored trial tested hydrazine sulfate alone versus placebo in the treatment of 127 patients with metastatic colorectal cancer.[8] In this trial, the patients who received hydrazine sulfate had, on average, shorter survival than the patients who received placebo, a finding that was statistically significant. There were no statistically significant differences between the hydrazine sulfate group and the placebo group with respect to weight gain or loss, anorexia, or quality of life.

Four other clinical trials did find some objective evidence of benefit with hydrazine sulfate therapy.[11,54,55,57] These trials had either nutritional status or metabolic status as the primary endpoint. In a placebo-controlled, randomized trial involving 38 patients with advanced disease, hydrazine sulfate was found to improve the abnormal glucose metabolism seen in cancer patients.[55] In another placebo-controlled, randomized trial that involved 101 patients with advanced cancer and weight loss, the use of hydrazine sulfate was associated with statistically significant improvements in appetite and either weight increase or weight maintenance.[54] However, the higher average caloric intake observed in this study for patients treated with hydrazine sulfate compared with patients treated with placebo was not statistically significant.[54] Two other clinical studies involving a total of 34 patients with either lung cancer or colon cancer found that hydrazine sulfate was able to reduce the body protein breakdown associated with cancer cachexia.[11,57] In view of the totality of evidence, the overall importance of the findings from these four clinical trials is not clear.

Finally, 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.

Adverse Effects

The side effects associated with hydrazine sulfate use have been mainly neurologic and gastrointestinal.[2,3,7,9,10,50-56] Nausea and/or vomiting, dizziness, and sensory and motor neuropathies have been reported.[2,3,7,9,10,50-56] The sensory and motor neuropathies have included paresthesias (abnormal touch sensations, such as burning or prickling, in the absence of external stimuli) of the upper and lower extremities (i.e., the arms and the legs, including the hands and the feet), polyneuritis (simultaneous inflammation of several peripheral nerves), and impaired fine motor function (e.g., an impaired ability to write).[3,10,51-53] Other side effects have included dry skin and/or itching, insomnia, and hypoglycemia.[2,3,51,53] One case of fatal liver and kidney failure and one case of severe encephalopathy (an injury to the brain) have been associated with the use of hydrazine sulfate.[59,60] In general, the side effects of hydrazine sulfate treatment 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.

Hydrazine sulfate is said to be incompatible with certain types of tranquilizers, barbiturates, alcohol, and foods high in tyramine content (e.g., aged cheeses and fermented products).[reviewed in 7,61] Use of these products reportedly decreases the effectiveness of hydrazine sulfate treatment and increases its side effects.[reviewed in 7,52,61]

Levels of Evidence for Human Studies of Cancer Complementary and Alternative Medicine

To assist readers in evaluating the results of human studies of CAM treatments for cancer, the strength of the evidence (i.e., the "levels of evidence") associated with each type of treatment is provided whenever possible. To qualify for a levels of evidence analysis, a study must 1) be published in a peer-reviewed, scientific journal; 2) report on a therapeutic outcome(s), such as tumor response, improvement in survival, or measured improvement in quality of life; and 3) describe clinical findings in sufficient detail that a meaningful evaluation can be made. 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. A table showing the levels of evidence scores for qualifying human studies cited in this summary is presented below. For an explanation of the scores and additional information about levels of evidence analysis of CAM treatments for cancer, please click on the following link: Levels of Evidence Analysis for Human Studies of Cancer Complementary and Alternative Medicine.

Glossary of Terms

adenocarcinoma: Cancer that begins in cells that line certain internal organs and that have glandular (secretory) properties.

analog: In chemistry, a substance that is similar, but not identical, to another.

anorexia: An abnormal loss of the appetite for food. Anorexia can be caused by cancer, AIDS, a mental disorder (i.e., anorexia nervosa), or other diseases.

anticachexia: Refers to a drug used to treat cachexia.

antidepressant: A drug used to treat depression.

antioxidant: A substance that prevents damage caused by free radicals. Free radicals are highly reactive chemicals that often contain oxygen. They are produced when molecules are split to give products that have unpaired electrons. This process is called oxidation.

antituberculosis: Refers to a drug used to treat tuberculosis.

astrocytoma: A tumor that begins in the brain or spinal cord in small, star-shaped cells called astrocytes.

bacteria: A large group of single-cell microorganisms associated with infections and disease in animals and humans. The singular of bacteria is bacterium.

barbiturate: A drug with sedative and hypnotic effects. Barbiturates have been used as sedatives and anesthetics, and they have been used to treat the convulsions associated with epilepsy.

benign: Not cancerous; does not invade nearby tissue or spread to other parts of the body.

bleomycin: An anticancer drug that belongs to the family of drugs called antitumor antibiotics.

cachexia: The loss of body weight and muscle mass frequently seen in patients with cancer, AIDS, or other diseases.

caloric intake: Refers to the number of calories (energy content) consumed.

carcinoma: Cancer that begins in skin or in tissues that line or cover internal organs.

carcinosarcoma: A malignant tumor that is a mixture of carcinoma (cancer of epithelial tissue, which is skin and tissue that lines or covers the internal organs) and sarcoma (cancer of connective tissue, such as bone, cartilage, and fat).

carmustine: An anticancer drug that belongs to the family of drugs called alkylating agents.

chemotherapy: Treatment with anticancer drugs.

chromosome: Part of a cell that contains genetic information. Except for sperm and eggs, all human cells contain 46 chromosomes.

clinical series: A case series in which the patients receive treatment in a clinic or other medical facility.

clinical trial: A research study that evaluates the effectiveness of new interventions in people. Each study is designed to evaluate new methods of screening, prevention, diagnosis, or treatment of a disease.

colorectal: Having to do with the colon or the rectum.

complementary and alternative medicine: CAM. Forms of treatment in addition to (complementary) or instead of (alternative) standard treatments. These practices include dietary supplements, megadose vitamins, herbal preparations, special teas, massage therapy, magnet therapy, spiritual healing, and meditation.

complete response: The disappearance of all signs of cancer. Also called a complete remission.

concurrent therapy: A treatment that is given at the same time as another.

cyclophosphamide: An anticancer drug that belongs to the family of drugs called alkylating agents.

derivative: In chemistry, a compound produced from or related to another.

dose-dependent: Refers to the effects of treatment with a drug. If the effects change when the dose of the drug is changed, the effects are said to be dose dependent.

encephalopathy: A disorder of the brain that can be caused by disease, injury, drugs, or chemicals.

enzyme: A protein that speeds up the rate at which chemical reactions take place in the body.

evaluable patients: Patients whose response to a treatment can be measured because enough information has been collected.

fluorouracil: An anticancer drug that belongs to the family of drugs called antimetabolites.

free radicals: Highly reactive chemicals that often contain oxygen and are produced when molecules are split to give products that have unpaired electrons. This process is called oxidation. Free radicals can damage important cellular molecules such as DNA or lipids or other parts of the cell.

gastrointestinal: Refers to the stomach and intestines.

glioblastoma: A general term that refers to malignant astrocytoma, a type of brain tumor.

gluconeogenesis: The process of making glucose (sugar) from its own breakdown products or from the breakdown products of lipids (fats) or proteins. Gluconeogenesis occurs mainly in cells of the liver or kidney.

herbicide: A chemical that kills plants.

Hodgkin's disease: A malignant disease of the lymphatic system that is characterized by painless enlargement of lymph nodes, the spleen, or other lymphatic tissue. It is sometimes accompanied by symptoms such as fever, weight loss, fatigue, and night sweats.

hydrogen peroxide: A chemical used in bleaches, dyes, cleansers, antiseptics, and disinfectants. In a concentrated form, it is toxic and irritating to tissues.

hypoglycemia: Abnormally low blood sugar.

inflammation: A response of redness, swelling, pain, and a feeling of heat in certain areas, which is meant to protect tissues affected by injury or disease.

insomnia: Inability to obtain adequate sleep.

leukemia: Cancer of blood-forming tissue.

lipid: Fat.

lymphosarcoma: An obsolete term for a malignant tumor of lymphatic tissue.

malignant: Cancerous; a growth with a tendency to invade and destroy nearby tissue and spread to other parts of the body.

melanoma: A form of skin cancer that arises in melanocytes, the cells that produce pigment. Melanoma usually begins in a mole.

meningioma: A type of tumor that occurs in the meninges, the membranes that cover and protect the brain and spinal cord. Meningiomas usually grow slowly.

metabolic: Having to do with metabolism.

metabolism: The total of all chemical changes that take place in a cell or an organism. These changes produce energy and basic materials that are needed for important life processes.

metastatic: Having to do with metastasis, which is the spread of cancer from one part of the body to another.

methotrexate: An anticancer drug that belongs to the family of drugs called antimetabolites.

microorganism: An organism that can be seen only through a microscope. Microorganisms include bacteria, protozoa, algae, and fungi. Although viruses are not considered living organisms, they are sometimes classified as microorganisms.

mitomycin: An anticancer drug that belongs to the family of drugs called antitumor antibiotics.

motor: In medicine, having to do with the movement of body parts.

mutation: Any change in the DNA of a cell. Mutations may be caused by mistakes during cell division, or they may be caused by exposure to DNA-damaging agents in the environment. Mutations can be harmful, beneficial, or have no effect. If they occur in cells that make eggs or sperm, they can be inherited; if they occur in other types of cells, they are not inherited. Certain mutations may lead to cancer or other diseases.

neurologic: Having to do with nerves or the nervous system.

neuropathy: A problem in any part of the nervous system except the brain and spinal cord. Neuropathies can be caused by infection, toxic substances, or disease.

non-small cell lung cancer: A group of lung cancers that includes squamous cell carcinoma, adenocarcinoma, and large cell carcinoma.

objective response: A measurable response.

paresthesias: Abnormal touch sensations, such as burning or prickling, that occur without an outside stimulus.

partial response: The shrinking, but not complete disappearance, of a tumor in response to therapy. Also called partial remission.

phase I trial: Phase I trials are the first step in testing a new treatment in humans. These studies test the best way to give a new treatment (for example, by mouth, intravenous infusion, or injection), and the best dose. The drug is usually given in progressively higher doses to determine the highest dose that does not cause harmful side effects. Because little is known about the possible risks and benefits of treatments being tested, phase I trials usually include only a limited number of patients who have not been helped by other known treatments.

pilot study: The initial study examining a new method or treatment.

placebo: An inactive substance that looks the same as, and is administered in the same way as, a drug in a clinical trial.

polyneuritis: Inflammation of several peripheral nerves at the same time.

procarbazine: An anticancer drug that belongs to the family of drugs called alkylating agents.

prognosis: The likely outcome or course of a disease; the chance of recovery.

quality of life : The overall enjoyment of life. Many clinical trials measure aspects of a person's sense of well-being and ability to perform various tasks in order to assess the effects that cancer and its treatment have on the person.

radiation therapy: The use of high-energy radiation from x-rays, neutrons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy) or from materials (radioisotopes) that produce radiation that are placed in or near a tumor or in the area where cancer cells are found (internal radiation therapy, implant radiation, or brachytherapy). Systemic radiation therapy involves giving a radioactive substance, such as a radiolabeled monoclonal antibody, that circulates throughout the body. Also called radiotherapy.

randomized clinical trial: A study in which the participants are assigned by chance to separate groups that compare different treatments. Neither the researcher nor the participant can choose the group. Using chance to assign people means that the groups will be similar and that the treatments they receive can be compared objectively. At the time of the trial, it is not known which of the treatments is best. It is the patient's choice to be in a randomized trial or not.

regression: A decrease in the extent or size of cancer.

retrospective: Looking back at events that have already taken place.

sensory: Having to do with the senses.

serum albumin: The main protein in blood plasma. Low levels of serum albumin occur in people with malnutrition, inflammation, and serious liver and kidney disease.

stable disease: Cancer that is not decreasing or increasing in extent or severity.

symptom: A sign that a person has a condition or disease. Some examples of symptoms are headache, fever, fatigue, nausea, vomiting, and pain.

therapeutic: Used to treat disease and help healing take place.

tumor model: A type of animal model which can be used to study the development and progression of diseases and to test new treatments before they are given to humans. Animals with transplanted human cancers or other tissues are called xenograft models.

tumor necrosis factor: A type of biological response modifier (a substance that can improve the body's natural response to disease).

tyramine: A derivative of the amino acid tyrosine.

uncontrolled study: A laboratory or clinical study that lacks a control or comparison group.

xenograft: The cells of one species transplanted to another species.

References:

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2. Spremulli E, Wampler GL, Regelson W. Clinical study of hydrazine sulfate in advanced cancer patients. Cancer Chemotherapy and Pharmacology 3(2):121- 124, 1979.

3. 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):1-10, 1975.

4. Toth B. A review of the antineoplastic action of certain hydrazines and hydrazine-containing natural products. In Vivo 10(1):65-96, 1996.

5. DeVita VT, Serpick A, Carbone PP. Preliminary clinical studies with ibenzmethyzin. Clinical Pharmacology and Therapeutics 7(4):542-546, 1966.

6. Samuels ML, Leary WV, Alexanian R, et al. Clinical trials with n- isopropyl-alpha-(2- methylhydrazino)-p-toluamide hydrochloride in malignant lymphoma and other disseminated neoplasia. Cancer 20(8):1187-1194, 1967.

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