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Hydrazine Sulfate (PDQ®)

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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.

Studies of Hydrazine Sulfate in Which Therapeutic Benefit Was Assesseda
Reference Citation(s) Type of Study Type of Cancer  No. of Patients: Enrolled; Treated; Controlb Strongest Benefit Reportedc Concurrent Therapyd Level of Evidence Scoree 
[1]Randomized clinical trialAdvanced nonsmall cell lung65; 32; 33, placeboNoneYes1iA
[4,15]Randomized clinical trialAdvanced nonsmall cell lung291; 135; 131, placeboNoneYes1iA
[5]Randomized clinical trialAdvanced colorectal128; 63; 64, placeboNoneNo1iA
[6]Randomized clinical trialAdvanced nonsmall cell lung243; 119; 118, placeboNoneYes1iA
[2]Nonconsecutive case series Various advanced25; 25; NoneSlight regression of some metastatic lesions, 1 patient with melanomaNo3iiiDiii
[3]Nonconsecutive case seriesVarious advanced158; 84; NoneMeasurable tumor regression, 7 patientsYes3iiiDiii
[7,9,10]Nonconsecutive case seriesVarious advanced763; 740; NoneComplete tumor regression, 6 patientsNo3iiiDiii
[8]Nonconsecutive case seriesVarious advanced25; 25; NoneNoneNo3iiiDiii
[11]Nonconsecutive case seriesVarious advanced32; 29; NoneNoneUnknown3iiiDiii
[12]Nonconsecutive case seriesVarious advanced101; 71; 30, placeboImproved weight maintenance or gain, 41 hydrazine sulfate treated vs. 17 placebo-treated patientsYes3iiiDiii
[18]Nonconsecutive case seriesGlioblastoma, astrocytoma, or meningiomaf465; 46; NoneImproved survival, patients with glioblastomaYesNoneg

No. = number.
aSee text for more details.
bNumber of patients treated plus number of control patients may not equal number of patients enrolled; number of patients enrolled = number of patients initially recruited/considered by the researchers who conducted a study; number of patients treated = number of enrolled patients who were given the treatment being studied AND for whom results were reported; historical control subjects are not included in number of patients enrolled.
cThe strongest evidence reported that the treatment under study has anticancer activity or otherwise improves the well-being of cancer patients. See text and glossary for definition of terms.
dSurgery, chemotherapy, or radiation therapy given/allowed at the same time as hydrazine sulfate treatment.
eFor information about levels of evidence analysis and an explanation of the level of evidence scores, see Levels of Evidence for Human Studies of Cancer Complementary and Alternative Medicine.
fThis study included six additional patients with benign brain tumors.
gInsufficient information given to permit a level of evidence analysis.

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]