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]
    
    

Glossary Terms

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.

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

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

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.

Treatment with drugs that kill cancer cells.

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.

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.

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.

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.

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

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.

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

A researcher in a clinical trial or clinical study.

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

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

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.

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

Having to do with nerves or the nervous system.

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.

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).

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.

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.

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

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.

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.

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.

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.

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