Hydrazine Sulfate Detailed Scientific Review

Overview

Background

Hydrazine sulfate is a chemical compound that has been used to treat cachexia, the weight loss and/or loss of appetite that sometimes accompanies advanced cancer. Secondarily, it has been proposed that it can stabilize and even cause some tumors to regress¹.

Dr. Joseph Gold, director of the Syracuse Cancer Research Institute in Syracuse, New York, is the developer of hydrazine sulfate treatment. Gold based his development on the work of Otto Warburg, winner of the Nobel Prize for medicine in 1931². According to Warburg’s findings, cachexia results from the abnormal metabolism of cancer cells. Gold experimented with several drugs and chemicals before isolating one that interrupted gluconeogenesis, hydrazine sulfate³.

Because hydrazine sulfate is a monoamine oxidase inhibitor (MAO), it is incompatible with tranquilizers, barbiturates, alcohol and other central nervous system depressants. It is also incompatible with foods that are high in tyramine, such as aged cheeses and other fermented products¹.

Proposed Mechanism of Action

Unlike normal cells that obtain most of their energy through respiration by taking in oxygen and giving off carbon dioxide, cancer cells obtain most of their energy through the fermentation of carbohydrates, a less efficient process. Fermentation is less efficient because it produces abnormally high levels of lactic acid as a waste product. The body must then expend energy reconverting this lactic acid back into glucose (gluconeogenesis) which is then utilized by the tumor. Thus, a self-perpetuating cycle is initiated that produces small amounts of energy for the tumor at the expense of relatively large amounts of energy from the host. Hydrazine sulfate (H₆N₂SO₄) blocks a liver enzyme, phosphoenolpyruvate carboxykinase, that is key to this process of gluconeogenesis^3,37.

Toxicity

When heated to decomposition, hydrazine sulfate emits toxic fumes of sulfur and nitrogen oxide⁴. Oral and injected doses have been associated with mild nausea, vomiting, anorexia and central nervous system toxicity⁴.

Hydrazine sulfate is a known antagonist of vitamin B₆ (pyridoxine)⁵ so symptoms of central nervous system toxicity are likely to occur. One case has been reported of severe encephalopathy (disease involving alterations of brain structure) associated with hydrazine sulfate in a patient taking it without physician consultation. Fortunately, the condition was reversed in this patient with high dose pyridoxine⁶.

Hydrazine sulfate has also been associated with liver and kidney failure resulting in the death of one patient who was also taking it without physician consultation⁵.

More information on the science and research in hydrazine sulfate therapy is provided in the Summary of Research.

Summary of Research

Amount and Type of Research

A search of the Medline database and other key databases (CINAHL, AltHealthWatch, SCOPUS) between 07/01/2004 and 05/15/2007 identified no new human studies. 

Two previous reviews have been conducted. Between 1/1/1997 and 6/30/2004, we identified eight articles that were relevant to hydrazine sulfate and treatment for cancer. Prior to 1997, we had identified 348 references, of which 201 (58%) were applicable to cancer and 154 (77%) had been retrieved.

Combining the results of these four searches has yielded a total of 209 applicable articles with 162 (78%) retrieved. We have classified these references into the following types of information:

*One article⁷ reported two studies: an in vitro and an animal study.
**One article was a chapter in a general reference concerning conventional and complementary therapies².

Of the human related articles, we coded the studies (23) by the following study designs:

Summary of Human Research

Literature reviews have identified 23 human studies on hydrazine sulfate (HS). Eight were randomized controlled trials (RCT) with seven of them double-blinded^8-14, and one of them an abstract of an unblinded randomized trial¹⁵. Ten were clinical series^4,16-24, and five were case reports^5,6,25-27.

Four of the seven RCTs assessed metabolic effects of hydrogen sulfate. A double-blind trial evaluating whole body protein breakdown reported that the placebo group experienced a slight rise in plasma-lysine flux while the HS group showed a significant fall. In addition, serum albumin fell in the placebo group, but was unchanged in the HS group¹². Another double-blind RCT assessed carbohydrate metabolism and reported a significantly improved glucose tolerance (p<0.05) in the HS group but not in the placebo group¹⁴. In a third double-blind RCT, the HS group had improved appetite and maintained or increased weight compared to the placebo group (p<0.05 each effect) ¹⁰. A fourth unblinded RCT¹⁵ reported significant improvements in abnormal glucose tolerance, glucose turnover, and protein turnover.

The National Cancer Institute (NCI) supported four RCTs which assessed survival and tumor response and all of these trials were double-blinded^8,9,11,13. One trial reported a survival advantage with HS for non-small cell lung cancer patients, but only for patients with the best performance status at the start of the trial (median survival 328 vs. 209 days, p< 0.05)¹¹. Considering all patients, median survival was still greater for the hydrazine vs. placebo group (292 days vs. 197 days), but the difference was not statistically significant (p= 0.11).

The other three RCTs sponsored by the NCI failed to demonstrate any statistically significant advantages to HS over placebo. One trial reported that the patients treated with HS showed no tumor regression in either group, a trend for poorer survival (p= 0.03) and a more rapid decline in performance status⁹. Another study found similar tumor response, toxicity, and quality of life results between all groups, but trends toward shorter time to progression and decreased survival in the HS group (p= 0.04)⁸. The third trial found no difference in survival, objective response rates, toxicity, anorexia, weight change or overall nutritional status. Also, quality of life was significantly worse in the HS group¹³.

This third NCI study reporting no advantage to HS¹³ was subsequently criticized because of the use of barbiturates by some patients²⁸. The authors responded by re-reviewing patient records and reported that only 12 of the 266 patients had actually received barbiturates (half for less than 48 hours). They did not, accordingly, change the original conclusions of the study²⁹. Additional difficulties associated with the analysis of this study, especially the quality of life endpoints, became the subject of a subsequent article³⁰. That analysis reported similar results for objective response rate, weight change and survival, but provided further details concerning the presence or absence of over 80 different types of toxicity. The only significant differences found in the different types of toxicity were that the HS group had significantly worse sensory and motor neuropathy³⁰.

One clinic series with historical controls reported improved survival of nine to 16 months for patients with malignant and benign brain tumors compared to the survivals of six months reported in the literature¹⁷.

Of nine uncontrolled clinical series, eight evaluated tumor responses and one evaluated metabolic effects. In three of the tumor response series, no significant objective improvements were reported^4,18,19, while five other studies reported objective or subjective improvement ^16,20-23. The one study of metabolic changes evaluated patients treated with chemotherapy (5-FU) and HS and reported that this combined therapy was associated with a significant reduction in fasting glucose level and plasma leucine appearance²⁴.

Two of five case reports noted regression of tumors and subjective improvement of one patient²⁶ and dramatic recovery of a terminal patient for at least six weeks²⁵. A third case report evaluated the gradual replacement of glucose-based Total Parenteral Nutrition (TPN) with lipid-based TPN plus HS. The tumor stabilized and one lesion slightly decreased²⁷.

Two case reports concerned serious adverse events: One patient developed encephalopathy that was reversed upon administration of vitamin B₆ (pyridoxine)⁶. Another patient died following hydrogen sulfate associated liver/renal failure⁵. (Both of these cases were patients who refused conventional cancer treatment and took hydrazine sulfate without consulting a physician.)

Conclusions

Significant reduction of weight loss may be possible based upon the positive results of two^10,20 out of three randomized trials^{10,20 9} that looked at this effect. Other positive metabolic effects have been demonstrated in three out of three randomized trials^12,14,15.

Improvement in survival is doubtful based upon no differences or negative effects found in three^9,11,13 out of four randomized and double-blinded trials that looked at this endpoint^8,9,11,13.

Improvement in quality of life is doubtful based upon two randomized controlled trials that reported worse quality of life effects in the patients taking hydrazine sulfate^9,13.

Serious toxicity can result if a physician does not monitor treatment within the context of a clinical trial.

The table below has brief summaries of the results of the human research studies reviewed.

Hydrazine Sulfate Human Studies Table

Human research studies are further described in the Annotated Bibliography.

Additional Reviews

Hydrogen Sulfate has also been reviewed by Gagnon and Bruera³¹, the Canadian Breast Cancer Research Initiative³² and the Office of Cancer Complementary and Alternative Medicine of the National Cancer Institute³³.

Annotated Bibliography

⁹Loprinzi CL, Kuross SA, O'Fallon JR, Gesme DH Jr, Gerstner JB, Rospond RM, et al. Randomized placebo-controlled evaluation of hydrazine sulfate in patients with advanced colorectal cancer. Journal of Clinical Oncology 1994 Jun;12(6):1121-5.

Purpose: Survival, tumor response and quality of life
Type of Study: RCT, double-blind
Methods: (Advanced colorectal) Patients with metastatic colon cancer (n=127) were randomized to receive hydrazine sulfate or placebo in a double-blind manner. Hydrazine sulfate was given to 63 patients and 64 served as the placebo group. Protocol patients did not concurrently receive any other systematic antineoplastic treatment.
Results: Survival curves showed poorer survival (p= 0.03) and poorer quality of life (p= 0.003) in the HS group. However, when a correction was made for the more rapid rate of death, the poorer performance status in the hydrazine sulfate group was no longer statistically significant. No significant differences occurred with regard to anorexia or weight loss.

¹³Kosty MP, Fleishman SB, Herndon II JE, Coughlin K, Kornblith AB, Scalzo A, 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. Journal of Clinical Oncology 1994 Jun;12(6):1113-20.

Purpose: Disease and symptom control
Type of Study: RCT
Methods: (Non-small-cell lung cancer) Patients with stage IIIB or IV NSCLC and performance status 0 or 1 were randomized to receive cisplastin, vinblastine and either HS 60 mg or placebo three times per day orally. There were 266 eligible patients, 135 in the treatment group and 131 in the placebo. Patients were required to have histologically or cytologically documented NSCLC with locally advanced disease (T4).
Results: The median survival duration was 7.78 months for the hydrazine sulfate treated group, compared with 7.70 for the placebo group (p= 0.65). Objective response rates were similar for both groups. HS group had 4% complete responses, 20% partial responses and 2% regression. The placebo group had 3% complete responses, 23% partial responses and 2% regression. The major toxicity was severe or life threatening neutropenia which occurred in 65% of the hydrazine sulfate patients and 63% of the placebo patients. There were no differences between groups in degree of anorexia, weight gain or loss of overall nutritional status. Sensory and motor neuropathy occurred significantly more often in patients treated with hydrazine sulfate and quality of life was significantly worse in these patients (p = .004).
Note: This trial was further analyzed in a subsequent article with discussion concerning choices of end points for quality of life analysis³⁰.

¹⁰Chlebowski RT, Bulcavage L, Grosvenor M, Tsunokai R, Block JB, Heber D, et al. Hydrazine sulfate in cancer patients with weight loss. A placebo-controlled clinical experience. Cancer 1987 Feb;59(3):406-10.

Purpose: Effects upon weight loss
Type of Study: RCT, double-blind
Methods: (Non-small-cell lung cancer) The criteria for inclusion in this trial were diagnosis of advanced cancer, weight loss greater than 10% from usual body weight, absence of severe hepatic or renal dysfunction and normal mental status. A total of 61 patients were randomly given hydrazine sulfate or placebo in a double blind fashion. An additional 40 patients received hydrazine sulfate and represented a consecutive series of patients seen in the Clinical Research Center.
Results: Hydrazine sulfate was evaluated using 24 hour dietary recalls and body weight before and after 30 days of either placebo or hydrazine oral administration in 101 heavily pretreated cancer patients with weight loss. After one month, 83% of hydrazine and only 53% of placebo patients completing repeat evaluation maintained or increased their weight (p <0.05). In addition, appetite improvement was more frequent in the hydrazine group (63% versus 25%, p<0.05). Although caloric intake was only slightly greater in hydrazine-treated patients, an increased caloric intake was more commonly associated with weight gain in patients receiving hydrazine compared with patients receiving placebo (81% versus 53%). Hydrazine toxicity was mild, with 71% of patients receiving no toxic effects. Hydrazine sulfate circulatory levels were obtained from a subset of 14 patients who completed 30 days of treatment and these mean maintenance hydrazine sulfate levels ranged from 0 to 89 ng/ml.

¹¹Chlebowski RT, Bulcavage L, Grosvenor M, Oktay E, Block JB, Chlebowski JS, et al. Hydrazine sulfate influence on nutritional status and survival in non-small-cell lung cancer. Journal of Clinical Oncology 1990 Jan;8(1):9-15.

Purpose: Effects upon nutritional status and survival
Type of Study: RCT, double-blind
Methods: (Non-small-cell lung cancer) Hydrazine sulfate was evaluated in this study under an Investigational New Drug (IND) authorization from the FDA. Patients were randomly assigned to receive the same chemotherapy regimen plus either placebo (n=33) or hydrazine sulfate (n=32).
Results: The pretreatment patient characteristics were comparable for both groups. Considering all patients, median survival was greater for the hydrazine versus placebo group (292 days versus 197 days), but the difference did not achieve statistical significance (p = 0.11). When analysis was limited to patients with an initially favorable performance status, survival was significantly prolonged in the hydrazine sulfate group (328 days versus 209 days, p <0.05). The authors concluded that further definitive studies were warranted.
Note: This study was subsequently criticized by Piantadosi in a letter to the journal in which he referred to the results as "the hazards of small trials" ³⁴. The journal then published a letter of rebuttal from Gold stating that many other smaller clinical trials reported in that same journal had not been criticized on the basis of their small size³⁵.

¹²Tayek JA, Heber D, Chlebowski RT. Effect of hydrazine sulphate on whole-body protein breakdown measured by ¹⁴C-lysine metabolism in lung cancer patients. Lancet 1987 Aug;2(8553):241-4.

Purpose: Effects upon whole-body protein breakdown
Type of Study: RCT
Methods: (Lung) Twelve patients with non-oat cell and one oat cell carcinoma were recruited over one year and randomized to receive 60 mg HS or placebo three times a day for one month. Fasting lysine flux was determined before and after one month.
Results: At baseline the groups were similar in terms of performance scores and sex distribution. Mean baseline plasma lysine-flux was 2580 (SD 580) mmol/hour for the placebo and 2510(450) mmol/h for the hydrazine group. After one month, the placebo group showed a slight rise to 2920 (450) mmol/h (p=0.08) and the hydrazine sulfate group showed a significant fall to 1840 (750) mmol/h (p<0.05). Mean serum albumin fell in the placebo group, but was unchanged in the hydrazine group.

¹⁴Chlebowski RT, Heber D, Richardson B, Block JB. Influence of hydrazine sulfate on abnormal carbohydrate metabolism in cancer patients with weight loss. Cancer Research 1984 Feb;44(2):857-61.

Purpose: Effects upon carbohydrate metabolism in cancer cachexia
Type of Study: RCT, double-blind placebo controlled
Methods: (Various cancers) Subjects were 38 patients with advanced cancer and weight loss. Patients with metastatic cancer were eligible for the study if they had lost 10% or more of their body weight and had normal liver function and mental status. After 30 days of treatment with capsules containing either placebo or hydrazine sulfate in 60 mg three times/day dosage, inpatient evaluation was evaluated.
Result: No statistically significant differences were observed between groups based upon pretreatment patient characteristics. Serial assessment of glucose tolerance showed no improvement after 30 days of placebo treatment, but significant improvement with 30 days of hydrazine sulfate (p<0.05). In addition, the rate of total glucose production was significantly decreased after 30 days of hydrazine sulfate compared to placebo treatment (p<0.05). Toxic effects of hydrazine sulfate were minimal. 

¹⁵Chlebowski R., Bulcavage L., Tayek J., et al. Metabolic "response frequency " associated with hydrazine sulfate versus placebo use in patients with advanced non-small cell lung cancer. Proc Am Assoc Cancer Res 1989;30:49. (abstract only)

Purpose: Effects upon glucose tolerance and protein turnover
Type of Study: RCT
Methods: (Advanced non-small cell lung) In a series of randomized trials, 72 patients with advanced NSCLC had determination of glucose tolerance, whole body glucose turnover and/or protein turnover before and 30 days after cisplatin combination chemotherapy treatment with addition of either placebo or HS (60 mg 3X/day).
Results: Mean baseline glucose tolerance and levels of glucose turnover and protein turnover of NSCLC patients were abnormal (p<0.05) compared to a cancer-free, age-matched control population. The authors concluded that these data demonstrated the feasibility of designing trials to definitively test the hypothesis that improvement in host metabolism is associated with clinical benefits for patients with NSCLC.
Caution Concerning This Report: This report was not published in a peer-reviewed journal; that is, it was not reviewed by experts in the field to determine that there was sufficient data to support the conclusions.

Uncontrolled Prospective Clinical Trials

¹⁸Lerner HJ, Regelson W. Clinical trial of hydrazine sulfate in solid tumors. Cancer Treatment Reports 1976 Jul;60(7):959-60.

Purpose: Disease response
Type of Study: Clinical series
Methods: All patients had biopsy-proven malignant disease at mixed sites and progression following chemotherapy. There were 25 evaluable patients (12 women and 13 men aged 45-79) with advanced measurable disease who were treated at the Pennsylvania hospital. All patients completed a course of treatment with hydrazine sulfate.
Results: All patients tolerated this drug regimen with a median until progression of 42 treatment days. In this series there was no evidence of myelosuppression or hepatic, cardiac or renal toxicity. There was infrequent, mild transitory nausea that did not require treatment. No patients reported improved increased appetite or sense of well being. Authors conclude that hydrazine sulfate failed to demonstrate objective or subjective antitumor activity.

¹⁶Filov VA, Gershanovich ML, Danova LA, Ivin BA. Experience of the treatment with Sehydrin (hydrazine sulfate, HS) in the advanced cancer patients. Investigational New Drugs 1995;13(1):89-97.

Purpose: Disease response, symptom control and toxicity
Type of Study: Clinical series
Methods: (Various advanced) For patients (n=740) aged from 16 to 73 years with progressive disseminated tumors for whom surgery, radiation or cytotoxic therapy was exhausted, HS was started 1.5 months after completion of previous therapy and after progression of the tumor was registered. Sehydrin was given three times a day, in tablets of 60 mg of substance purified by repeated crystallization with constituents (1.0 g of NaCl).
Results: Complete regression of the tumors (primary, recurrent and metastatic) with the duration of effect from six months to nine years in six cases. A therapeutic effect of Sehydrin was detected only after the repeated (two to three) courses. Partial responses were observed in 25 of 740 patients who were resistant to combined chemotherapy. In 47 patients, tumor regression not exceeding 25%, considered no change, was observed. Interruption of the tumor progression during the administration of Sehydrin for the period of more than three months was observed in 216 out of 740 patients (29.2%). The objective responses and stabilization of the tumor growth occurred in patients at the terminal stage of disease. The drug was well tolerated by patients in primary and subsequent courses and did not induce myelosuppression or other significant side effects. Sehydrin may be assessed as an alternative drug for patients when other methods of treatment can not be used.

¹⁷ Filov VA, Gershanovich ML, Ivin BA, Danova LA, Gurchin FA, Naryshkin AG, et al. Treatment of primary brain tumors with Sehydrin. Voprosy Onkologii 1994;40(7-12):332-6.

Purpose: Disease response
Type of Study: Clinical series
Methods: (Brain) Patients (n=52) from ages six to 62 were investigated; 46 out of the 52 had high-grade malignancies with recurrence after surgery. Hydrogen sulfate (Sehydrin) was administered in 60 mg enteric coated tablets three times daily for 30-40 days. Children six to 12 years old were given 30 mg three times daily.
Results: Complete regression (CR) of neurological symptoms occurred in 63.5% of the patients, which increased to 73.1% if partial regression (PR) of neurological symptoms was included. The percentages for patients with malignant tumors only were 60.8% of those who achieved complete responses and 71.1% of those who achieved partial responses. Sehydrin had virtually no significant untoward side effects.

¹⁹Spremulli E, Wampler GL, Regelson W. Clinical study of hydrazine sulfate in advanced cancer patients. Cancer Chemotherapy & Pharmacology 1979;3(2):121-4.

Purpose: Disease response
Type of Study: Clinical series
Methods: Twenty-five patients with mixed cancers were treated with hydrazine sulfate as a single agent. Hydrazine sulfate was orally given in the form of 60-mg capsules from one to four times daily.
Results: Toxicity was minimal. No patient had a 50% reduction of tumor size, and no significant responses were seen in the treatment group. Subjective benefit was seen in three patients but it was of brief duration. The authors concluded that hydrazine sulfate as given in their study was an inactive compound.

⁴Ochoa M Jr, Wittes RE, Krakoff IH. Trial of hydrazine sulfate (NSC-150014) in patients with cancer. Cancer Chemotherapy Reports - Part 1975 Nov-1975 Dec;59(6):1151-4.

Purpose: Disease response
Type of Study: Clinical series
Methods: (Various cancers) All patients (n=32) had disseminated nonresectable measurable disease. Hydrazine sulfate was administered in gelatin capsules by mouth, one half to two hours before meals. Single doses were administered in midmorning and multiple doses separated by five hours. The dosage was subsequently increased in selected patients after evaluation of the response and toxicity. All patients were examined daily by one of the researchers in addition to the physician of record by physical examination, laboratory determination or both.
Results: In 29 of 32 patients, a biopharmacologic activity or biochemical change that could be attributed to the drug was observed by one week (three of the 32 patients were considered not adequately treated). Of the 25 who received therapy for two weeks all showed clinical or pharmacologic changes that could be attributed to the administration of hydrazine sulfate. There were no significant subjective improvements or antitumor responses in any of the 29 patients adequately treated with hydrazine sulfate.
Note: Dr. Gold, the developer of hydrogen sulfate treatment, criticized the methodology of this study because all patients were close to death at the time of entry on to the study rather than having an expected survival of at least two months as specified in the protocol³⁶.

²⁰Gershanovich ML, Danova LA, Ivin BA, Filov VA. Results of clinical study antitumor action of hydrazine sulfate. Nutrition & Cancer 1981;3(1):7-12.

Purpose: Disease response
Type of Study: Clinical series
Methods: Hydrazine sulfate was administered to patients (n=233) with disseminated tumors at mixed sites via tablet or gelatin 60 mg three times daily for a period of one to 1.5 months and sometimes up to six months. Repeated therapeutic courses from two to 24 were interspersed by 14 to 30 day intervals of cessation.
Results: Tumor regression of over 50% was noted in some patients with neuroblastoma, lung cancer, advanced Hodgkin's disease and recurrent desmosarcoma. Significant tumor stabilization occurred in 42.2% of the patients. Sixty-five percent had favorable symptomatic effects: improvement of appetite, weight stabilization and gain and reduced weakness, pain and fever. Side effects (dizziness, vomiting and dyspepsia) occurred in 22%. No hypotensive, cardiotoxic, nephrotoxic or myelodepressive effects were noted.

²¹Gold J. Use of hydrazine sulfate in terminal and preterminal cancer patients: results of investigational new drug (IND) study in 84 evaluable patients. Oncology 1975;32(1):1-10.

Purpose: Disease response
Type of Study: Clinical series
Methods: (Various cancers) Patients (n=158) with disseminated cancers no longer responding to chemotherapy and/or radiation were treated with hydrazine sulfate.
Results: Only 84 cases were evaluable, and 70% of these cases improved subjectively and 17% improved objectively. Of the remaining cases with either concurrent or prior anticancer therapy, improvements occurred only after the addition of hydrazine sulfate to the treatment regimen.

²⁴Tayek JA, Sutter L, Manglik S, Lillington LB, Grosvenor M, Chlebowski RT. Altered metabolism and mortality in patients with colon cancer receiving chemotherapy. American Journal of the Medical Sciences 1995 Aug;310(2):48-55.

Purpose: Metabolic effects and survival
Type of Study: Clinical series
Methods: (Colon) Patients with colon cancer (n=22) were admitted prospectively to a clinical research center for combined therapy of 5-fluorouracil and hydrazine sulfate. Serial measurements were made of counter-regulatory hormones, fasting hepatic glucose production (HGP), intravenous glucose tolerance test, plasma leucine appearance (LA) and leucine oxidation.
Results: This combination treatment was associated with a significant reduction in fasting glucose level (p<0.025) without a significant fall in fasting HGP. The decreased fasting glucose value was associated with a mild, but not statistically improved glucose disposal rate in response to the intravenous glucose tolerance test (p<0.15). Plasma leucine appearance was significantly reduced after two months of therapy (p < 0.025). Plasma LA was related directly to length of survival time while baseline HGP, carcinoembryonic antigen and insulin concentration were related inversely to survival. The authors stated that further research was required to validate the predictability of these baseline metabolic markers with survival.

²³Gold J. Use of hydrazine sulfate in advanced cancer patients: Preliminary results. Proc Am Ass Cancer Res 1974;15(#332):83.

Purpose: Disease response and side effects
Type of Study: Clinical series
Methods: Patients (n=10) with mixed cancers
Results: Six patients improved, two died and two remained unchanged. Side effects were minimal.
Caution Concerning This Report: This report was not published in a peer-reviewed journal; that is, it was not reviewed by experts in the field to determine that there was sufficient data to support the conclusions. In addition, the report consists of preliminary results.

²²Gershanovich ML, Danova LA, Kondratyev VB, Malyugina LL, Stukov AN, Seitz JF, et al. Clinical data on the antitumor activity of hydrazine sulfate. Cancer Treatment Reports 1976 Jul;60(7):933-5.

Purpose: Disease response
Type of Study: Clinical series
Methods: Hydrogen sulfate (HS) was given to 102 patients with extensive solid malignant tumors in various locations who had previously received surgical treatment, radiotherapy or chemotherapy. Evaluation of the antitumor effect was definitively performed >1.5 months after the start of HS treatment by direct measurement of the tumor and roentgenographic and endoscopic examinations.
Results: No complete responses were recorded. Partial responses (PR) with continuation of the effect for at least a month were observed in three patients. Symptomatic effects of HS were reduction of fever, tendency toward normalization of lab findings, reduction or disappearance of hemoptysis and diminished respiratory deficiency.

²⁵Bridgman NM. A new life for my cancer patient. Journal of Practical Nursing 1988 Mar;38(1):38-41.

Reference List

1. Syracuse Cancer Research Institute I. Hydrazine Sulfate. [Web Page]. (Accessed 2007 May 17).
2. Lerner M. Does hydrazine sulfate prevent weight loss and extend life with cancer? Choices in Healing. Chapter 22:433-41.
3. Gold J. Cancer cachexia and gluconeogenesis. Annals of the New York Academy of Sciences 1974 Mar;230:103-10.
4. Ochoa M Jr, Wittes RE, Krakoff IH. Trial of hydrazine sulfate (NSC-150014) in patients with cancer. Cancer Chemotherapy Reports - Part 1975 Nov-1975 Dec;59(6):1151-4.
5. Hainer MI, Tsai N, Komura ST, Chiu CL. Fatal hepatorenal failure associated with hydrazine sulfate. Annals of Internal Medicine 2000;133(11):877-80.
6. Nagappan R, Riddell T. Pyridoxine therapy in a patient with severe hydrazine sulfate toxicity. Intensive Care Medicine 2000;28(6):2116-8.
7. Kamradt JM, Pienta KJ. The effect of hydrazine sulfate on prostate cancer growth. Oncology Reports 1998;5:919-21.
8. Loprinzi CL, Goldberg RM, Su JQ, Mailliard JA, Kuross SA, Maksymiuk AW, et al. Placebo-controlled trial of hydrazine sulfate in patients with newly diagnosed non-small-cell lung cancer. Journal of Clinical Oncology 1994 Jun;12(6):1126-9.
9. Loprinzi CL, Kuross SA, O'Fallon JR, Gesme DH Jr, Gerstner JB, Rospond RM, et al. Randomized placebo-controlled evaluation of hydrazine sulfate in patients with advanced colorectal cancer. Journal of Clinical Oncology 1994 Jun;12(6):1121-5.
10. Chlebowski RT, Bulcavage L, Grosvenor M, Tsunokai R, Block JB, Heber D, et al. Hydrazine sulfate in cancer patients with weight loss. A placebo-controlled clinical experience. Cancer 1987 Feb;59(3):406-10.
11. Chlebowski RT, Bulcavage L, Grosvenor M, Oktay E, Block JB, Chlebowski JS, et al. Hydrazine sulfate influence on nutritional status and survival in non-small-cell lung cancer. Journal of Clinical Oncology 1990 Jan;8(1):9-15.
12. 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 1987 Aug;2(8553):241-4.
13. Kosty MP, Fleishman SB, Herndon II JE, Coughlin K, Kornblith AB, Scalzo A, 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. Journal of Clinical Oncology 1994 Jun;12(6):1113-20.
14. Chlebowski RT, Heber D, Richardson B, Block JB. Influence of hydrazine sulfate on abnormal carbohydrate metabolism in cancer patients with weight loss. Cancer Research 1984 Feb;44(2):857-61.
15. Chlebowski R., Bulcavage L., Tayek J., et al. Metabolic "response frequency " associated with hydrazine sulfate versus placebo use in patients with advanced non-small cell lung cancer. Proc Am Assoc Cancer Res 1989;30:49.
16. Filov VA, Gershanovich ML, Danova LA, Ivin BA. Experience of the treatment with Sehydrin (hydrazine sulfate, HS) in the advanced cancer patients. Investigational New Drugs 1995;13(1):89-97.
17. Filov VA, Gershanovich ML, Ivin BA, Danova LA, Gurchin FA, Naryshkin AG, et al. Treatment of primary brain tumors with Sehydrin. Voprosy Onkologii 1994;40(7-12):332-6.
18. Lerner HJ, Regelson W. Clinical trial of hydrazine sulfate in solid tumors. Cancer Treatment Reports 1976 Jul;60(7):959-60.
19. Spremulli E, Wampler GL, Regelson W. Clinical study of hydrazine sulfate in advanced cancer patients. Cancer Chemotherapy & Pharmacology 1979;3(2):121-4.
20. Gershanovich ML, Danova LA, Ivin BA, Filov VA. Results of clinical study antitumor action of hydrazine sulfate. Nutrition & Cancer 1981;3(1):7-12.
21. Gold J. Use of hydrazine sulfate in terminal and preterminal cancer patients: results of investigational new drug (IND) study in 84 evaluable patients. Oncology 1975;32(1):1-10.
22. Gershanovich ML, Danova LA, Kondratyev VB, Malyugina LL, Stukov AN, Seitz JF, et al. Clinical data on the antitumor activity of hydrazine sulfate. Cancer Treatment Reports 1976 Jul;60(7):933-5.
23. Gold J. Use of hydrazine sulfate in advanced cancer patients: Preliminary results. Proc Am Ass Cancer Res 1974;15(#332):83.
24. Tayek JA, Sutter L, Manglik S, Lillington LB, Grosvenor M, Chlebowski RT. Altered metabolism and mortality in patients with colon cancer receiving chemotherapy. American Journal of the Medical Sciences 1995 Aug;310(2):48-55.
25. Bridgman NM. A new life for my cancer patient. Journal of Practical Nursing 1988 Mar;38(1):38-41.
26. Gold J. Remission of metastatic giant cell tumor (GCT) by hydrazine sulfate and vitamin K₃ therapy. Proc Am Ass Cancer Res 1987;28(#915):230.
27. Bozzetti F CLGCeal. Total nutritional manipulation in humans: Report of a Cancer Patient. Clinical Nutrition 1996;15:207-9.
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