Purpose of This PDQ Summary
Overview
General Information
History
Laboratory/Animal/Preclinical Studies
Human/Clinical Studies
Adverse Effects
Overall Level of Evidence for Hydrazine Sulfate
Changes to This Summary (05/20/2008)
More Information

Purpose of This PDQ Summary

This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the use of hydrazine sulfate as a treatment for cancer. The summary is reviewed regularly and updated as necessary by the PDQ Cancer Complementary and Alternative Medicine Editorial Board ¹.

Information about the following is included in this summary:

• A brief history of hydrazine sulfate research.
• The results of clinical studies of hydrazine sulfate.
• Possible side effects of hydrazine sulfate use.

This summary is intended as a resource to inform and assist clinicians and other health professionals who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.

Some of the reference citations in the summary are accompanied by a level of evidence designation. These designations are intended to help the readers assess the strength of the evidence supporting the use of specific interventions or treatment strategies. The PDQ Cancer Complementary and Alternative Medicine Editorial Board uses a formal evidence ranking system ² in developing its level of evidence designations. These designations should not be used as a basis for reimbursement determinations.

This summary is also available in a patient version ³, which is written in less technical language.

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.

This summary contains the following key information:

• Hydrazine sulfate is a chemical that has been studied as a treatment for cancer and as a treatment for the body wasting (i.e., cachexia) associated with this disease.
• 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 it causes cancer.
• There is only limited evidence from animal studies that hydrazine sulfate has anticancer activity.
• Hydrazine sulfate has shown no anticancer activity in randomized clinical trials, and data concerning its effectiveness in treating cancer-related cachexia are inconclusive.
• Hydrazine sulfate has been marketed in the United States as a dietary supplement or a nutraceutical by some companies; however, its use as an anticancer drug outside of clinical trials has not been approved by the U.S. Food and Drug Administration.

Many of the medical and scientific terms used in the summary are hypertext linked (at first use in each section) to the NCI Web site Dictionary ⁴, which is oriented toward nonexperts. When a linked term is clicked, a definition will appear in a separate window. All linked terms and their corresponding definitions will appear in a glossary in the printable version of the summary.

Reference citations in some PDQ CAM information summaries may include links to external Web sites 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 Web sites, or of any treatment or product, by the PDQ Cancer CAM Editorial Board or the National Cancer Institute.

General Information

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. To date, the FDA has granted IND status to at least three groups of researchers 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 cancer patients, hydrazine sulfate has been administered in pills or capsules. Reviewed in [4] In the clinical studies conducted thus far, the dose and the duration of hydrazine sulfate administration have varied.

References

1. Chlebowski RT, Bulcavage L, Grosvenor M, et al.: Hydrazine sulfate influence on nutritional status and survival in non-small-cell lung cancer. J Clin Oncol 8 (1): 9-15, 1990.  [PUBMED Abstract]
   
   
2. Spremulli E, Wampler GL, Regelson W: Clinical study of hydrazine sulfate in advanced cancer patients. Cancer Chemother Pharmacol 3 (2): 121-4, 1979.  [PUBMED Abstract]
   
   
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.  [PUBMED Abstract]
   
   
4. Toth B: A review of the antineoplastic action of certain hydrazines and hydrazine-containing natural products. In Vivo 10 (1): 65-96, 1996 Jan-Feb.  [PUBMED Abstract]
   
   

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 [1] 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 [1] Of the 82 tested compounds, seven showed activity against human tumor cells and were, therefore, selected for further testing in pilot studies and phase I clinical trials. Reviewed in [1] 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 disease, melanoma, and lung carcinoma, and it was ultimately used in several first-line treatment regimens in the 1960s.[2,3] Reviewed in [1] 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.[4-9]

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 [10-12] 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.[1,10,12-21] In the 10th Report on Carcinogens, 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.”[22] 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.[17,23] Reviewed in [14] Hydrazine compounds have been reported to cause mutations and chromosome damage in bacteria and in plant and animal cells. Reviewed in [10]

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.[24] Reviewed in [25-29] 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.[24] Reviewed in [25-30] 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.[24] Reviewed in [25-30]

In the second proposed mechanism, hydrazine sulfate inhibits tumor necrosis factor (TNF)-alpha activity.[31-34] TNF-alpha, which is also known as cachectin, is one of a number of substances normally produced by white blood cells in the body in response to infection by microorganisms and in response to other stimuli such as tissue damage. Reviewed in [31,32,34-36] Higher-than-normal TNF-alpha production has been observed in white blood cells obtained from cancer patients. Reviewed in [35-37] It has been suggested that higher-than-normal levels of TNF-alpha can cause the anorexia, increased energy expenditure, and increased muscle protein breakdown seen in cancer patients. Reviewed in [31,35-37] Some of the muscle protein breakdown products would become available for gluconeogenesis. Inhibition of TNF-alpha activity might, therefore, inhibit tumor growth and prevent cachexia.

References

1. Toth B: A review of the antineoplastic action of certain hydrazines and hydrazine-containing natural products. In Vivo 10 (1): 65-96, 1996 Jan-Feb.  [PUBMED Abstract]
   
   
2. DeVita VT, Serpick A, Carbone PP: Preliminary clinical studies with ibenzmethyzin. Clin Pharmacol Ther 7 (4): 542-6, 1966 Jul-Aug.  [PUBMED Abstract]
   
   
3. 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): 1187-94, 1967.  [PUBMED Abstract]
   
   
4. Chlebowski RT, Bulcavage L, Grosvenor M, et al.: Hydrazine sulfate influence on nutritional status and survival in non-small-cell lung cancer. J Clin Oncol 8 (1): 9-15, 1990.  [PUBMED Abstract]
   
   
5. Kosty MP, Fleishman SB, Herndon JE 2nd, 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 12 (6): 1113-20, 1994.  [PUBMED Abstract]
   
   
6. Loprinzi CL, Kuross SA, O'Fallon JR, et al.: Randomized placebo-controlled evaluation of hydrazine sulfate in patients with advanced colorectal cancer. J Clin Oncol 12 (6): 1121-5, 1994.  [PUBMED Abstract]
   
   
7. Loprinzi CL, Goldberg RM, Su JQ, et al.: Placebo-controlled trial of hydrazine sulfate in patients with newly diagnosed non-small-cell lung cancer. J Clin Oncol 12 (6): 1126-9, 1994.  [PUBMED Abstract]
   
   
8. Filov VA, Gershanovich ML, Danova LA, et al.: Experience of the treatment with Sehydrin (Hydrazine Sulfate, HS) in the advanced cancer patients. Invest New Drugs 13 (1): 89-97, 1995.  [PUBMED Abstract]
   
   
9. Tayek JA, Sutter L, Manglik S, et al.: Altered metabolism and mortality in patients with colon cancer receiving chemotherapy. Am J Med Sci 310 (2): 48-55, 1995.  [PUBMED Abstract]
   
   
10. Kimball RF: The mutagenicity of hydrazine and some of its derivatives. Mutat Res 39 (2): 111-26, 1977.  [PUBMED Abstract]
    
    
11. Nelson SD, Gordon WP: Metabolic activation of hydrazines. Adv Exp Med Biol 136 Pt B: 971-81, 1981.  [PUBMED Abstract]
    
    
12. Vasudeva M, Vashishat RK: Mutagenic and recombinogenic activity of hydrazine sulphate in Saccharomyces cerevisiae. Mutat Res 155 (3): 113-5, 1985.  [PUBMED Abstract]
    
    
13. Toth B: Synthetic and naturally occurring hydrazines as possible cancer causative agents. Cancer Res 35 (12): 3693-7, 1975.  [PUBMED Abstract]
    
    
14. Rosenkranz HS, Carr HS: Hydrazine antidepressants and isoniazid: potential carcinogens. Lancet 1 (7713): 1354-5, 1971.  [PUBMED Abstract]
    
    
15. Douglas GR, Gingerich JD, Soper LM: Evidence for in vivo non-mutagenicity of the carcinogen hydrazine sulfate in target tissues of lacZ transgenic mice. Carcinogenesis 16 (4): 801-4, 1995.  [PUBMED Abstract]
    
    
16. Quintero-Ruiz A, Paz-Neri LL, Villa-Treviño S: Indirect alkylation of CBA mouse liver DNA and RNA by hydrazine in vivo. A possible mechanism of action as a carcinogen. J Natl Cancer Inst 67 (3): 613-8, 1981.  [PUBMED Abstract]
    
    
17. Freese E, Sklarow S, Freese EB: DNA damage caused by antidepressant hydrazines and related drugs. Mutat Res 5 (3): 343-8, 1968 May-Jun.  [PUBMED Abstract]
    
    
18. Bhide SV, D'Souza RA, Sawai MM, et al.: Lung tumour incidence in mice treated with hydrazine sulphate. Int J Cancer 18 (4): 530-5, 1976.  [PUBMED Abstract]
    
    
19. Severi L, Biancifiori C: Hepatic carcinogenesis in CBA-Cb-Se mice and Cb-Se rats by isonicotinic acid hydrazide and hydrazine sulfate. J Natl Cancer Inst 41 (2): 331-49, 1968.  [PUBMED Abstract]
    
    
20. Toth B: Lung tumor induction and inhibition of breast adenocarcinomas by hydrazine sulfate in mice. J Natl Cancer Inst 42 (3): 469-75, 1969.  [PUBMED Abstract]
    
    
21. Menon MM, Bhide SV: Perinatal carcinogenicity of isoniazid (INH) in Swiss mice. J Cancer Res Clin Oncol 105 (3): 258-61, 1983.  [PUBMED Abstract]
    
    
22. National Institute of Environmental Health Sciences.: 11th Report on Carcinogens. Research Triangle Park, NC: U.S. Department of Health and Human Services, Public Health Service, National Toxicology Program, 2005. Available online. ⁵ Last accessed May 19, 2008. 
    
    
23. National Toxicology Program.: Hydrazine and hydrazine sulfate. Rep Carcinog 10: 138-9, 2002.  [PUBMED Abstract]
    
    
24. Ray PD, Hanson RL, Lardy HA: Inhibition by hydrazine of gluconeogenesis in the rat. J Biol Chem 245 (4): 690-6, 1970.  [PUBMED Abstract]
    
    
25. Gold J: Inhibition of Walker 256 intramuscular carcinoma in rats by administration of hydrazine sulfate. Oncology 25 (1): 66-71, 1971.  [PUBMED Abstract]
    
    
26. 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 27 (1): 69-80, 1973.  [PUBMED Abstract]
    
    
27. Gold J: Anabolic profiles in late-stage cancer patients responsive to hydrazine sulfate. Nutr Cancer 3 (1): 13-9, 1981.  [PUBMED Abstract]
    
    
28. Gold J: Hydrazine sulfate: a current perspective. Nutr Cancer 9 (2-3): 59-66, 1987.  [PUBMED Abstract]
    
    
29. Dills WL Jr: Nutritional and physiological consequences of tumour glycolysis. Parasitology 107 (Suppl): S177-86, 1993.  [PUBMED Abstract]
    
    
30. Gold J: Proposed treatment of cancer by inhibition of gluconeogenesis. Oncology 22 (2): 185-207, 1968.  [PUBMED Abstract]
    
    
31. Hughes TK, Cadet P, Larned CS: Modulation of tumor necrosis factor activities by a potential anticachexia compound, hydrazine sulfate. Int J Immunopharmacol 11 (5): 501-7, 1989.  [PUBMED Abstract]
    
    
32. De SK, Silverstein R, Andrews GK: Hydrazine sulfate protection against endotoxin lethality: analysis of effects on expression of hepatic cytokine genes and an acute-phase gene. Microb Pathog 13 (1): 37-47, 1992.  [PUBMED Abstract]
    
    
33. Johnson DC, Freudenberg MA, Jia F, et al.: Contribution of tumor necrosis factor-alpha and glucocorticoid in hydrazine sulfate-mediated protection against endotoxin lethality. Circ Shock 43 (1): 1-8, 1994.  [PUBMED Abstract]
    
    
34. Jia F, Morrison DC, Silverstein R: Hydrazine sulfate selectively modulates the TNF response to endotoxin in mouse macrophages. Circ Shock 42 (2): 111-4, 1994.  [PUBMED Abstract]
    
    
35. Parnes HL, Aisner J: Protein calorie malnutrition and cancer therapy. Drug Saf 7 (6): 404-16, 1992 Nov-Dec.  [PUBMED Abstract]
    
    
36. Lowry SF, Moldawer LL: Tumor necrosis factor and other cytokines in the pathogenesis of cancer cachexia. Princ Pract Oncol Updates 4(8): 1-12, 1990. 
    
    
37. Bruera E: Current pharmacological management of anorexia in cancer patients. Oncology (Huntingt) 6 (1): 125-30; discussion 132, 137, 1992.  [PUBMED Abstract]
    
    

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.[1-9] Reviewed in [10,11] Substantial increases in tumor incidence were observed in most studies that used rats, mice, or hamsters.[1-5,7-9] Hydrazine administration was associated with increases in lung, liver, and breast tumors in rats,[2,5] increases in lung and liver tumors in mice,[1-4,8] and increases in liver tumors in hamsters.[7,9] 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.[3]

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.[12-18] 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.[12-14] Hydrazine sulfate alone had no effect on solid tumors formed from L-1210 leukemia cells in mice.[13] 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.[17] Findings from a third laboratory demonstrated that hydrazine sulfate alone had no effect on the growth of Dunning prostate cancer tumors in rats.[18]

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.[12-14] 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, fluorouracil [5-FU], carmustine [BCNU], or neocarcinostatin) to treat Walker 256 carcinosarcoma tumors in rats and solid L-1210 leukemia tumors in mice.[13-15] 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.[13] As indicated previously, hydrazine sulfate alone had no effect against solid L-1210 tumors.[13]

Addition of the drug clofibrate to the hydrazine sulfate plus chemotherapy drug combinations was reported to produce even greater antitumor effects.[15] 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 [15] This three drug treatment regimen, however, was tested against only one type of tumor (Walker 256 carcinosarcomas in rats).[15]

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.[17] When hydrazine sulfate was combined with the drug phloridzin, which is similar to phloretin, using the same two tumor models, no increase in anticancer activity was observed.[17] 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.[16]

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 [19] In view of these results, NCI recommended against further evaluation of hydrazine sulfate as an anticancer agent. Reviewed in [19] However, clinical investigation of this compound continued, largely because of its potential as a treatment for cancer-related anorexia and cachexia.

References

1. Bhide SV, D'Souza RA, Sawai MM, et al.: Lung tumour incidence in mice treated with hydrazine sulphate. Int J Cancer 18 (4): 530-5, 1976.  [PUBMED Abstract]
   
   
2. Severi L, Biancifiori C: Hepatic carcinogenesis in CBA-Cb-Se mice and Cb-Se rats by isonicotinic acid hydrazide and hydrazine sulfate. J Natl Cancer Inst 41 (2): 331-49, 1968.  [PUBMED Abstract]
   
   
3. Toth B: Lung tumor induction and inhibition of breast adenocarcinomas by hydrazine sulfate in mice. J Natl Cancer Inst 42 (3): 469-75, 1969.  [PUBMED Abstract]
   
   
4. Menon MM, Bhide SV: Perinatal carcinogenicity of isoniazid (INH) in Swiss mice. J Cancer Res Clin Oncol 105 (3): 258-61, 1983.  [PUBMED Abstract]
   
   
5. Biancifiori C, Giornelli-Santilli FE, Milia U, et al.: Pulmonary tumours in rats induced by oral hydrazine sulphate. Nature 212 (60): 414-5, 1966.  [PUBMED Abstract]
   
   
6. Toth B: Tumorigenesis studies with 1,2-dimethylhydrazine dihydrochloride, hydrazine sulfate, and isonicotinic acid in golden hamsters. Cancer Res 32 (4): 804-7, 1972.  [PUBMED Abstract]
   
   
7. Shimizu H, Toth B: Effect of lifetime administration of 2-hydroxyethylhydrazine on tumorigenesis in hamsters and mice. J Natl Cancer Inst 52 (3): 903-6, 1974.  [PUBMED Abstract]
   
   
8. Maru GB, Bhide SV: Effect of antioxidants and antitoxicants of isoniazid on the formation of lung tumours in mice by isoniazid and hydrazine sulphate. Cancer Lett 17 (1): 75-80, 1982.  [PUBMED Abstract]
   
   
9. Bosan WS, Shank RC, MacEwen JD, et al.: Methylation of DNA guanine during the course of induction of liver cancer in hamsters by hydrazine or dimethylnitrosamine. Carcinogenesis 8 (3): 439-44, 1987.  [PUBMED Abstract]
   
   
10. Toth B: Synthetic and naturally occurring hydrazines as possible cancer causative agents. Cancer Res 35 (12): 3693-7, 1975.  [PUBMED Abstract]
    
    
11. National Toxicology Program.: Hydrazine and hydrazine sulfate. Rep Carcinog 10: 138-9, 2002.  [PUBMED Abstract]
    
    
12. Gold J: Inhibition of Walker 256 intramuscular carcinoma in rats by administration of hydrazine sulfate. Oncology 25 (1): 66-71, 1971.  [PUBMED Abstract]
    
    
13. 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 27 (1): 69-80, 1973.  [PUBMED Abstract]
    
    
14. Gold J: Enhancement by hydrazine sulfate of antitumor effectiveness of cytoxan, mitomycin C, methotrexate and bleomycin, in walker 256 carcinosarcoma in rats. Oncology 31 (1): 44-53, 1975.  [PUBMED Abstract]
    
    
15. Gold J: Potentiation by clofibrate of in-vivo tumor inhibition by hydrazine sulfate and cytotoxic agents, in Walker 256 carcinosarcoma. Cancer Biochem Biophys 3 (1): 41-5, 1978.  [PUBMED Abstract]
    
    
16. Dilman VM, Anisimov VN: Potentiation of antitumor effect of cyclophosphamide and hydrazine sulfate by treatment with the antidiabetic agent, 1-phenylethylbiguanide (phenformin). Cancer Lett 7 (6): 357-61, 1979.  [PUBMED Abstract]
    
    
17. Nelson JA, Falk RE: The efficacy of phloridzin and phloretin on tumor cell growth. Anticancer Res 13 (6A): 2287-92, 1993 Nov-Dec.  [PUBMED Abstract]
    
    
18. Kamradt JM, Pienta KJ: The effect of hydrazine sulfate on prostate cancer growth. Oncol Rep 5 (4): 919-21, 1998 Jul-Aug.  [PUBMED Abstract]
    
    
19. Henney JE: Unproven methods of cancer treatment. In: DeVita VT, Hellman S, Rosenberg SA, eds.: Cancer: Principles and Practice of Oncology. 2nd ed. Philadelphia, Pa: JB Lippincott Company, 1985, pp 2333-44. 
    
    

Human/Clinical Studies

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,[1-13] b) changes in body weight,[1-6,8,10-12,14] c) carefully measured quality of life,[4-6,15] and d) changes in nutritional or metabolic status.[1,4,12,13,16,17] Clinical studies of hydrazine sulfate have been funded by a pharmaceutical company,[3] the Russian government,[7,9,10,18] and by grants from the National Cancer Institute (NCI).[1,2,4-6,8,11,12,15,16] They have also been sponsored by the North Central Cancer Treatment Group (NCCTG) [5,6] and the Cancer and Leukemia Group B (CALGB).[4,15]

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.[9] 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.[10] It appears that the 225 patients described in this second report [10] included the 95 patients described in the first report.[9] Partial responses and stable disease were reported for 4 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.[7] Once again, it appears that 225 of these 740 patients were described in the earlier reports.[9,10] 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.[18] These patients were not described in the other reports.[7,9,10] 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.[18]

Evaluation of the findings from these Russian clinical series [7,9,10,18] 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.[2,8,11] 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.[1,4-6,15] In these trials, survival,[1,4-6,15] objective tumor response,[1,4,15] and carefully measured quality of life [4-6,15] were major endpoints.

One of the trials involved 65 patients with advanced nonsmall 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 nonsmall cell lung cancer.[4,15] 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 nonsmall cell lung cancer was also evaluated in an NCCTG-sponsored trial.[6] 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.[5] 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.[12,13,16,17] 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.[13] 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.[12] 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.[12] 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.[16,17] In view of the totality of evidence, the overall importance of the findings from these four clinical trials is not clear.

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.

References

1. Chlebowski RT, Bulcavage L, Grosvenor M, et al.: Hydrazine sulfate influence on nutritional status and survival in non-small-cell lung cancer. J Clin Oncol 8 (1): 9-15, 1990.  [PUBMED Abstract]
   
   
2. Spremulli E, Wampler GL, Regelson W: Clinical study of hydrazine sulfate in advanced cancer patients. Cancer Chemother Pharmacol 3 (2): 121-4, 1979.  [PUBMED Abstract]
   
   
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.  [PUBMED Abstract]
   
   
4. Kosty MP, Fleishman SB, Herndon JE 2nd, 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 12 (6): 1113-20, 1994.  [PUBMED Abstract]
   
   
5. Loprinzi CL, Kuross SA, O'Fallon JR, et al.: Randomized placebo-controlled evaluation of hydrazine sulfate in patients with advanced colorectal cancer. J Clin Oncol 12 (6): 1121-5, 1994.  [PUBMED Abstract]
   
   
6. Loprinzi CL, Goldberg RM, Su JQ, et al.: Placebo-controlled trial of hydrazine sulfate in patients with newly diagnosed non-small-cell lung cancer. J Clin Oncol 12 (6): 1126-9, 1994.  [PUBMED Abstract]
   
   
7. Filov VA, Gershanovich ML, Danova LA, et al.: Experience of the treatment with Sehydrin (Hydrazine Sulfate, HS) in the advanced cancer patients. Invest New Drugs 13 (1): 89-97, 1995.  [PUBMED Abstract]
   
   
8. Lerner HJ, Regelson W: Clinical trial of hydrazine sulfate in solid tumors. Cancer Treat Rep 60 (7): 959-60, 1976.  [PUBMED Abstract]
   
   
9. Gershanovich ML, Danova LA, Kondratyev VB, et al.: Clinical data on the antitumor activity of hydrazine sulfate. Cancer Treat Rep 60 (7): 933-5, 1976.  [PUBMED Abstract]
   
   
10. Gershanovich ML, Danova LA, Ivin BA, et al.: Results of clinical study antitumor action of hydrazine sulfate. Nutr Cancer 3 (1): 7-12, 1981.  [PUBMED Abstract]
    
    
11. Ochoa M Jr, Wittes RE, Krakoff IH: Trial of hydrazine sulfate (NSC-150014) in patients with cancer. Cancer Chemother Rep 59 (6): 1151-4, 1975 Nov-Dec.  [PUBMED Abstract]
    
    
12. Chlebowski RT, Bulcavage L, Grosvenor M, et al.: Hydrazine sulfate in cancer patients with weight loss. A placebo-controlled clinical experience. Cancer 59 (3): 406-10, 1987.  [PUBMED Abstract]
    
    
13. Chlebowski RT, Heber D, Richardson B, et al.: Influence of hydrazine sulfate on abnormal carbohydrate metabolism in cancer patients with weight loss. Cancer Res 44 (2): 857-61, 1984.  [PUBMED Abstract]
    
    
14. Gold J: Anabolic profiles in late-stage cancer patients responsive to hydrazine sulfate. Nutr Cancer 3 (1): 13-9, 1981.  [PUBMED Abstract]
    
    
15. Herndon JE 2nd, Fleishman S, Kosty MP, et al.: A longitudinal study of quality of life in advanced non-small cell lung cancer: Cancer and Leukemia Group B (CALGB) 8931. Control Clin Trials 18 (4): 286-300, 1997.  [PUBMED Abstract]
    
    
16. Tayek JA, Sutter L, Manglik S, et al.: Altered metabolism and mortality in patients with colon cancer receiving chemotherapy. Am J Med Sci 310 (2): 48-55, 1995.  [PUBMED Abstract]
    
    
17. Tayek JA, Heber D, Chlebowski RT: Effect of hydrazine sulphate on whole-body protein breakdown measured by 14C-lysine metabolism in lung cancer patients. Lancet 2 (8553): 241-4, 1987.  [PUBMED Abstract]
    
    
18. Filov VA, Gershanovich ML, Ivin BA, et al.: [Therapy of primary brain tumors with segidrin] Vopr Onkol 40 (7-12): 332-6, 1994.  [PUBMED Abstract]
    
    

Adverse Effects

The side effects associated with hydrazine sulfate use have been mainly gastrointestinal and neurologic.[1-12] Nausea and/or vomiting, dizziness, and sensory and motor neuropathies have been reported.[1-12] 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).[2,5,7-9] Other side effects have included dry skin and/or itching, insomnia, and hypoglycemia.[1,2,7,9] 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.[13,14] The former case involved a man aged 55 years with squamous cell carcinoma of the maximillary sinus who purchased hydrazine sulfate from a source found on the Internet and proceeded to take it without medical advice or supervision. After 4 months he presented with evidence of renal and liver toxicity, which eventually resulted in death. This case highlights the danger of accessing materials and medical information on the Internet and proceeding with self- medication without seeking proper medical advice and supervision.[15]

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.[16-18] Reviewed in [19]

References

1. Spremulli E, Wampler GL, Regelson W: Clinical study of hydrazine sulfate in advanced cancer patients. Cancer Chemother Pharmacol 3 (2): 121-4, 1979.  [PUBMED Abstract]
   
   
2. 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.  [PUBMED Abstract]
   
   
3. Kosty MP, Fleishman SB, Herndon JE 2nd, 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 12 (6): 1113-20, 1994.  [PUBMED Abstract]
   
   
4. Loprinzi CL, Goldberg RM, Su JQ, et al.: Placebo-controlled trial of hydrazine sulfate in patients with newly diagnosed non-small-cell lung cancer. J Clin Oncol 12 (6): 1126-9, 1994.  [PUBMED Abstract]
   
   
5. Filov VA, Gershanovich ML, Danova LA, et al.: Experience of the treatment with Sehydrin (Hydrazine Sulfate, HS) in the advanced cancer patients. Invest New Drugs 13 (1): 89-97, 1995.  [PUBMED Abstract]
   
   
6. Lerner HJ, Regelson W: Clinical trial of hydrazine sulfate in solid tumors. Cancer Treat Rep 60 (7): 959-60, 1976.  [PUBMED Abstract]
   
   
7. Gershanovich ML, Danova LA, Kondratyev VB, et al.: Clinical data on the antitumor activity of hydrazine sulfate. Cancer Treat Rep 60 (7): 933-5, 1976.  [PUBMED Abstract]
   
   
8. Gershanovich ML, Danova LA, Ivin BA, et al.: Results of clinical study antitumor action of hydrazine sulfate. Nutr Cancer 3 (1): 7-12, 1981.  [PUBMED Abstract]
   
   
9. Ochoa M Jr, Wittes RE, Krakoff IH: Trial of hydrazine sulfate (NSC-150014) in patients with cancer. Cancer Chemother Rep 59 (6): 1151-4, 1975 Nov-Dec.  [PUBMED Abstract]
   
   
10. Chlebowski RT, Bulcavage L, Grosvenor M, et al.: Hydrazine sulfate in cancer patients with weight loss. A placebo-controlled clinical experience. Cancer 59 (3): 406-10, 1987.  [PUBMED Abstract]
    
    
11. Chlebowski RT, Heber D, Richardson B, et al.: Influence of hydrazine sulfate on abnormal carbohydrate metabolism in cancer patients with weight loss. Cancer Res 44 (2): 857-61, 1984.  [PUBMED Abstract]
    
    
12. Herndon JE 2nd, Fleishman S, Kosty MP, et al.: A longitudinal study of quality of life in advanced non-small cell lung cancer: Cancer and Leukemia Group B (CALGB) 8931. Control Clin Trials 18 (4): 286-300, 1997.  [PUBMED Abstract]
    
    
13. Hainer MI, Tsai N, Komura ST, et al.: Fatal hepatorenal failure associated with hydrazine sulfate. Ann Intern Med 133 (11): 877-80, 2000.  [PUBMED Abstract]
    
    
14. Nagappan R, Riddell T: Pyridoxine therapy in a patient with severe hydrazine sulfate toxicity. Crit Care Med 28 (6): 2116-8, 2000.  [PUBMED Abstract]
    
    
15. Black M, Hussain H: Hydrazine, cancer, the Internet, isoniazid, and the liver. Ann Intern Med 133 (11): 911-3, 2000.  [PUBMED Abstract]
    
    
16. Masaki H, Arai H, Torii K: Newly developed animal model with alcoholic liver damage induced by an inhibitor for gluconeogenesis, hydrazine sulfate. Gastroenterol Jpn 24 (5): 584, 1989.  [PUBMED Abstract]
    
    
17. Suzuki H, Tominaga T, Mizuno H, et al.: Ethanol and hydrazine sulfate induced chronic hepatic injury in rats: the curative effect of administration of glucogenic amino acids. Alcohol Alcohol Suppl 1A: 111-7, 1993.  [PUBMED Abstract]
    
    
18. Gold J: Incompatibility of hydrazine sulfate and pentobarbital in the treatment of tumor bearing animals. [Abstract] Proc Am Assoc Cancer Res 18: A-999, 250, 1977. 
    
    
19. U.S. General Accounting Office.: Cancer Drug Research: Contrary to Allegation, NIH Hydrazine Sulfate Studies Were Not Flawed. Washington, DC: U.S. General Accounting Office, 1995, GAO-HEHS-95-141. Also available online. ⁷ Last accessed May 19, 2008. 
    
    

Overall Level of Evidence for Hydrazine Sulfate

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 Cancer Complementary and Alternative Medicine ².

Changes to This Summary (05/20/2008)

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.

Adverse Effects ⁸

Added text ⁹ about a man aged 55 years with squamous cell carcinoma of the maximillary sinus who purchased hydrazine sulfate from a source found on the Internet and proceeded to take it without medical advice or supervision (cited Black et al. as reference 15).

More Information

Additional Information about CAM Therapies

• The National Center for Complementary and Alternative Medicine ¹⁰ (NCCAM).
• The National Cancer Institute Office of Cancer Complementary and Alternative Medicine ¹¹ (OCCAM).
• CAM on PubMed ¹², a special subset of the PubMed scientific literature database created through a partnership between NCCAM and the National Library of Medicine.

About PDQ

• PDQ® - NCI's Comprehensive Cancer Database ¹³

  Full description of the NCI PDQ database.

Other PDQ Summaries

• PDQ® Cancer Information Summaries: Adult Treatment ¹⁴

  Treatment options for adult cancers.

• PDQ® Cancer Information Summaries: Pediatric Treatment ¹⁵

  Treatment options for childhood cancers.

• PDQ® Cancer Information Summaries: Supportive and Palliative Care ¹⁶

  Side effects of cancer treatment, management of cancer-related complications and pain, and psychosocial concerns.

• PDQ® Cancer Information Summaries: Screening/Detection (Testing for Cancer) ¹⁷

  Tests or procedures that detect specific types of cancer.

• PDQ® Cancer Information Summaries: Prevention ¹⁸

  Risk factors and methods to increase chances of preventing specific types of cancer.

• PDQ® Cancer Information Summaries: Genetics ¹⁹

  Genetics of specific cancers and inherited cancer syndromes, and ethical, legal, and social concerns.

• PDQ® Cancer Information Summaries: Complementary and Alternative Medicine ²⁰

  Information about complementary and alternative forms of treatment for patients with cancer.

Important:

This information is intended mainly for use by doctors and other health care professionals. If you have questions about this topic, you can ask your doctor, or call the Cancer Information Service at 1-800-4-CANCER (1-800-422-6237).

Glossary Terms

Cancer that begins in cells that line certain internal organs and that have gland-like (secretory) properties.

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

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.

Describes a drug or effect that works against cachexia (loss of body weight and muscle mass).

A drug used to treat depression.

A substance that protects cells from the damage caused by free radicals (unstable molecules made by the process of oxidation during normal metabolism). Free radicals may play a part in cancer, heart disease, stroke, and other diseases of aging. Antioxidants include beta-carotene, lycopene, vitamins A, C, and E, and other natural and manufactured substances.

Describes a drug or effect that works against tuberculosis (a contagious bacterial infection that usually affects the lungs).

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

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

A drug used to treat insomnia, seizures, and convulsions, and to relieve anxiety and tension before surgery. It belongs to the family of drugs called central nervous system (CNS) depressants.

Not cancerous. Benign tumors may grow larger but do not spread to other parts of the body. Also called nonmalignant.

The organ that stores urine.

The active ingredient in a drug that is used to treat many types of cancer and is being studied in the treatment of other types of cancer. It comes from the bacterium Streptomyces verticillus. Bleomycin damages DNA and may kill rapidly growing cancer cells. It is a type of antineoplastic antibiotic.

Glandular organ located on the chest. The breast is made up of connective tissue, fat, and breast tissue that contains the glands that can make milk. Also called mammary gland.

Loss of body weight and muscle mass, and weakness that may occur in patients with cancer, AIDS, or other chronic diseases.

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

A term for diseases in which abnormal cells divide without control and can invade nearby tissues. Cancer cells can also spread to other parts of the body through the blood and lymph systems. There are several main types of cancer. Carcinoma is a cancer that begins in the skin or in tissues that line or cover internal organs. Sarcoma is a cancer that begins in bone, cartilage, fat, muscle, blood vessels, or other connective or supportive tissue. Leukemia is a cancer that starts in blood-forming tissue such as the bone marrow, and causes large numbers of abnormal blood cells to be produced and enter the blood. Lymphoma and multiple myeloma are cancers that begin in the cells of the immune system. Central nervous system cancers are cancers that begin in the tissues of the brain and spinal cord. Also called malignancy.

Any substance that causes cancer.

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

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).

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

A group or series of case reports involving patients who were given similar treatment. Reports of case series usually contain detailed information about the individual patients. This includes demographic information (for example, age, gender, ethnic origin) and information on diagnosis, treatment, response to treatment, and follow-up after treatment.

The individual unit that makes up the tissues of the body. All living things are made up of one or more cells.

Treatment with drugs that kill cancer cells.

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

Having to do with the examination and treatment of patients.

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

A type of research study that tests how well new medical approaches work in people. These studies test new methods of screening, prevention, diagnosis, or treatment of a disease. Also called clinical trial.

A type of research study that tests how well new medical approaches work in people. These studies test new methods of screening, prevention, diagnosis, or treatment of a disease. Also called clinical study.

The longest part of the large intestine, which is a tube-like organ connected to the small intestine at one end and the anus at the other. The colon removes water and some nutrients and electrolytes from partially digested food. The remaining material, solid waste called stool, moves through the colon to the rectum and leaves the body through the anus.

Having to do with the colon or the rectum.

Forms of treatment that are used in addition to (complementary) or instead of (alternative) standard treatments. These practices generally are not considered standard medical approaches. Standard treatments go through a long and careful research process to prove they are safe and effective, but less is known about most types of CAM. CAM may include dietary supplements, megadose vitamins, herbal preparations, special teas, acupuncture, massage therapy, magnet therapy, spiritual healing, and meditation. Also called CAM.

The disappearance of all signs of cancer in response to treatment. This does not always mean the cancer has been cured. Also called complete remission.

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

In a clinical trial, the group that does not receive the new treatment being studied. This group is compared to the group that receives the new treatment, to see if the new treatment works.

A drug that is used to treat many types of cancer and is being studied in the treatment of other types of cancer. It is also used to treat some types of kidney disease in children. Cyclophosphamide attaches to DNA in cells and may kill cancer cells. It is a type of alkylating agent. Also called CTX and Cytoxan.

The molecules inside cells that carry genetic information and pass it from one generation to the next. Also called DNA.

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

A product that is added to the diet. A dietary supplement is taken by mouth, and usually contains one or more dietary ingredient (such as vitamin, mineral, herb, amino acid, and enzyme). Also called nutritional supplement.

The amount of medicine taken, or radiation given, at one time.

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.

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

In clinical trials, an event or outcome that can be measured objectively to determine whether the intervention being studied is beneficial. The endpoints of a clinical trial are usually included in the study objectives. Some examples of endpoints are survival, improvements in quality of life, relief of symptoms, and disappearance of the tumor.

A protein that speeds up chemical reactions in the body.

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

Initial treatment used to reduce a cancer. First-line therapy is followed by other treatments, such as chemotherapy, radiation therapy, and hormone therapy to get rid of cancer that remains. Also called induction therapy, primary therapy, and primary treatment.

A drug used to treat symptoms of cancer of the colon, breast, stomach, and pancreas. It is also used in a cream to treat certain skin conditions. Fluorouracil stops cells from making DNA and it may kill cancer cells. It is a type of antimetabolite. Also called 5-fluorouracil and 5-FU.

A highly reactive chemical that often contains oxygen and is produced when molecules are split to give products that have unpaired electrons (a process called oxidation). Free radicals can damage important cellular molecules such as DNA or lipids or other parts of the cell.

Refers to the stomach and intestines. Also called GI.

A fast-growing type of central nervous system tumor that forms from glial (supportive) tissue of the brain and spinal cord and has cells that look very different from normal cells. Glioblastoma usually occurs in adults and affects the brain more often than the spinal cord. Also called GBM, glioblastoma multiforme, and grade IV astrocytoma.

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.

A type of sugar; the chief source of energy for living organisms.

A chemical that kills plants.

A cancer of the immune system that is marked by the presence of a type of cell called the Reed-Sternberg cell. The two major types of Hodgkin disease are classical Hodgkin lymphoma and nodular lymphocyte-predominant Hodgkin lymphoma. Symptoms include the painless enlargement of lymph nodes, spleen, or other immune tissue. Other symptoms include fever, weight loss, fatigue, or night sweats. Also called Hodgkin lymphoma.

A substance that has been studied as a treatment for cancer and as a treatment for cachexia (body wasting) associated with advanced cancer.

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

Abnormally low blood sugar.

Invasion and multiplication of germs in the body. Infections can occur in any part of the body and can spread throughout the body. The germs may be bacteria, viruses, yeast, or fungi. They can cause a fever and other problems, depending on where the infection occurs. When the body’s natural defense system is strong, it can often fight the germs and prevent infection. Some cancer treatments can weaken the natural defense system.

Redness, swelling, pain, and/or a feeling of heat in an area of the body. This is a protective reaction to injury, disease, or irritation of the tissues.

Use of a syringe and needle to push fluids or drugs into the body; often called a "shot."

Difficulty in going to sleep or getting enough sleep.

In clinical trials, refers to a drug (including a new drug, dose, combination, or route of administration) or procedure that has undergone basic laboratory testing and received approval from the U.S. Food and Drug Administration (FDA) to be tested in human subjects. A drug or procedure may be approved by the FDA for use in one disease or condition, but be considered investigational in other diseases or conditions. Also called experimental.

A researcher in a clinical trial or clinical study.

A condition in which the kidneys stop working and are not able to remove waste and extra water from the blood or keep body chemicals in balance. Acute or severe kidney failure happens suddenly (for example, after an injury) and may be treated and cured. Chronic kidney failure develops over many years, may be caused by conditions like high blood pressure or diabetes, and cannot be cured. Chronic kidney failure may lead to total and long-lasting kidney failure, called end-stage renal disease (ESRD). A person in ESRD needs dialysis (the process of cleaning the blood by passing it through a membrane or filter) or a kidney transplant. Also called renal failure.

Cancer that starts in blood-forming tissue such as the bone marrow and causes large numbers of blood cells to be produced and enter the bloodstream.

A ranking system used to describe the strength of the results measured in a clinical trial or research study. The design of the study (such as a case report for an individual patient or a randomized double-blinded controlled clinical trial) and the endpoints measured (such as survival or quality of life) affect the strength of the evidence.

Fat.

A large organ located in the upper abdomen. The liver cleanses the blood and aids in digestion by secreting bile.

One of a pair of organs in the chest that supplies the body with oxygen, and removes carbon dioxide from the body.

An obsolete term for a malignant tumor of lymphatic tissue.

Cancerous. Malignant tumors can invade and destroy nearby tissue and spread to other parts of the body.

Having to do with the breast.

A legal drug that is used to prevent, treat, or relieve symptoms of a disease or abnormal condition.

A form of cancer that begins in melanocytes (cells that make the pigment melanin). It may begin in a mole (skin melanoma), but can also begin in other pigmented tissues, such as in the eye or in the intestines.

A type of slow-growing tumor that forms in the meninges (thin layers of tissue that cover and protect the brain and spinal cord). Meningiomas usually occur in adults.

Having to do with metabolism (the total of all chemical changes that take place in a cell or an organism to produce energy and basic materials needed for important life processes).

Having to do with metastasis, which is the spread of cancer from the primary site (place where it started) to other places in the body.

A drug used to treat some types of cancer, rheumatoid arthritis, and severe skin conditions, such as psoriasis. Methotrexate stops cells from making DNA and may kill cancer cells. It is a type of antimetabolite. Also called amethopterin, MTX, and Rheumatrex.

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.

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

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

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 mutations occur in other types of cells, they are not inherited. Certain mutations may lead to cancer or other diseases.

The National Cancer Institute, part of the National Institutes of Health of the United States Department of Health and Human Services, is the Federal Government's principal agency for cancer research. The National Cancer Institute conducts, coordinates, and funds cancer research, training, health information dissemination, and other programs with respect to the cause, diagnosis, prevention, and treatment of cancer. Access the National Cancer Institute Web site at http://www.cancer.gov. Also called NCI.

A feeling of sickness or discomfort in the stomach that may come with an urge to vomit. Nausea is a side effect of some types of cancer therapy.

Having to do with nerves or the nervous system.

A nerve problem that causes pain, numbness, tingling, swelling, or muscle weakness in different parts of the body. It usually begins in the hands or feet and gets worse over time. Neuropathy may be caused by physical injury, infection, toxic substances, disease (such as cancer, diabetes, kidney failure, or malnutrition), or drugs, including anticancer drugs. Also called peripheral neuropathy.

A group of lung cancers that are named for the kinds of cells found in the cancer and how the cells look under a microscope. The three main types of non-small cell lung cancer are squamous cell carcinoma, large cell carcinoma, and adenocarcinoma. Non-small cell lung cancer is the most common kind of lung cancer.

A clinical study that includes some, but not all, of the eligible patients identified by the researchers during the study registration period. This type of study does not usually have a control group.

A food or dietary supplement that is believed to provide health benefits.

A chemical compound (such as protein, fat, carbohydrate, vitamin, or mineral) contained in foods. These compounds are used by the body to function and grow.

An improvement that can be measured by the health care provider (for example, when a tumor shrinks or there are fewer cancer cells in the blood).

An abnormal touch sensation, such as burning or prickling, that occurs without an outside stimulus.

A decrease in the size of a tumor, or in the extent of cancer in the body, in response to treatment. Also called partial remission.

PDQ is an online database developed and maintained by the National Cancer Institute. Designed to make the most current, credible, and accurate cancer information available to health professionals and the public, PDQ contains peer-reviewed summaries on cancer treatment, screening, prevention, genetics, complementary and alternative medicine, and supportive care; a registry of cancer clinical trials from around the world; and directories of physicians, professionals who provide genetics services, and organizations that provide cancer care. Most of this information, and more specific information about PDQ, can be found on the NCI's Web site at http://www.cancer.gov/cancertopics/pdq. Also called Physician Data Query.

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 dose is usually increased a little at a time in order to find the highest dose that does not cause harmful side effects. Because little is known about the possible risks and benefits of the treatments being tested, phase I trials usually include only a small number of patients who have not been helped by other treatments.

The initial study examining a new method or treatment.

An inactive substance or treatment that looks the same as, and is given the same way as, an active drug or treatment being tested. The effects of the active drug or treatment are compared to the effects of the placebo.

Refers to a clinical study in which the control patients receive a placebo.

Inflammation of several peripheral nerves at the same time.

Research using animals to find out if a drug, procedure, or treatment is likely to be useful. Preclinical studies take place before any testing in humans is done.

The active ingredient in a drug that is used to treat advanced Hodgkin lymphoma and is being studied in the treatment of other types of cancer. Procarbazine blocks cells from making proteins and damages DNA. It may kill cancer cells. It is a type of antineoplastic agent and a type of alkylating agent.

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

A gland in the male reproductive system. The prostate surrounds the part of the urethra (the tube that empties the bladder) just below the bladder, and produces a fluid that forms part of the semen.

A molecule made up of amino acids that are needed for the body to function properly. Proteins are the basis of body structures such as skin and hair and of substances such as enzymes, cytokines, and antibodies.

The overall enjoyment of life. Many clinical trials assess the effects of cancer and its treatment on the quality of life. These studies measure aspects of an individual’s sense of well-being and ability to carry out various activities.

The use of high-energy radiation from x-rays, gamma rays, neutrons, protons, and other sources to kill cancer cells and shrink tumors. Radiation may come from a machine outside the body (external-beam radiation therapy), or it may come from radioactive material placed in the body near cancer cells (internal radiation therapy). Systemic radiation therapy uses a radioactive substance, such as a radiolabeled monoclonal antibody, that travels in the blood to tissues throughout the body. Also called irradiation and radiotherapy.

A study in which the participants are assigned by chance to separate groups that compare different treatments; neither the researchers nor the participants can choose which group. Using chance to assign people to groups 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 treatment is best. It is the patient's choice to be in a randomized trial.

A treatment plan that specifies the dosage, the schedule, and the duration of treatment.

A decrease in the size of a tumor or in the extent of cancer in the body.

In medicine, an improvement related to treatment.

Looking back at events that have already taken place.

A person who has studied science, especially one who is active in a particular field of investigation.

Convulsion; a sudden, involuntary movement of the muscles.

Having to do with the senses.

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

A problem that occurs when treatment affects healthy tissues or organs. Some common side effects of cancer treatment are fatigue, pain, nausea, vomiting, decreased blood cell counts, hair loss, and mouth sores.

An abnormal mass of tissue that usually does not contain cysts or liquid areas. Solid tumors may be benign (not cancer), or malignant (cancer). Different types of solid tumors are named for the type of cells that form them. Examples of solid tumors are sarcomas, carcinomas, and lymphomas. Leukemias (cancers of the blood) generally do not form solid tumors.

Cancer that begins in squamous cells, which are thin, flat cells that look like fish scales. Squamous cells are found in the tissue that forms the surface of the skin, the lining of the hollow organs of the body, and the passages of the respiratory and digestive tracts. Also called epidermoid carcinoma.

Cancer that is neither decreasing nor increasing in extent or severity.

Describes a mathematical measure of difference between groups. The difference is said to be statistically significant if it is greater than what might be expected to happen by chance alone. Also called significant.

An improvement that is reported by the patient, but cannot be measured by the healthcare provider (for example, "I feel better").

A procedure to remove or repair a part of the body or to find out whether disease is present. An operation.

An indication that a person has a condition or disease. Some examples of symptoms are headache, fever, fatigue, nausea, vomiting, and pain.

Having to do with poison or something harmful to the body. Toxic substances usually cause unwanted side effects.

The extent to which something is poisonous or harmful.

An abnormal mass of tissue that results when cells divide more than they should or do not die when they should. Tumors may be benign (not cancer), or malignant (cancer). Also called neoplasm.

Cells, tissues, or animals used to study the development and progression of cancer, and to test new treatments before they are given to humans. Animals with transplanted human tumors or other tissues are called xenograft models.

A protein made by white blood cells in response to an antigen (substance that causes the immune system to make a specific immune response) or infection. Tumor necrosis factor can also be made in the laboratory. It may boost a person’s immune response, and also may cause necrosis (cell death) of some types of tumor cells. Tumor necrosis factor is being studied in the treatment of some types of cancer. It is a type of cytokine. Also called TNF.

A clinical study that lacks a comparison (i.e., a control) group.

To eject some or all of the contents of the stomach through the mouth.

A type of immune cell. Most white blood cells are made in the bone marrow and are found in the blood and lymph tissue. White blood cells help the body fight infections and other diseases. Granulocytes, monocytes, and lymphocytes are white blood cells. Also called leukocyte and WBC.

The transplant of an organ, tissue, or cells to an individual of another species.