Hydrazine Sulfate, Part 2

by National Cancer Institute

(Page 2 of 2)

6. Have any clinical trials (research studies with people) of hydrazine sulfate been conducted?

Clinical trials are a type of research study that tests how well new medical treatments or other interventions work in people. Hydrazine sulfate has been studied extensively in patients with advanced cancer. Researchers have evaluated the following:

• Tumor response and/or survival among patients with various types of cancer.
• Changes in body weight.
• Quality of life.
• Changes in nutritional status and metabolism (chemical changes that take place in cells and produce energy needed for an organism to function).

Clinical studies of hydrazine sulfate have been sponsored by a pharmaceutical company, the Russian government, and NCI. Clinical trials have been sponsored by the North Central Cancer Treatment Group (NCCTG) and the Cancer and Leukemia Group B (CALGB), which are part of NCI's Clinical Trials Cooperative Group Program. Cooperative groups work with NCI to identify important questions in cancer research and to design carefully controlled clinical trials to answer these questions.

In the mid 1970s, a pharmaceutical company conducted the first clinical tests of hydrazine sulfate as a treatment for cancer. The researchers found that a small number of patients who were treated with hydrazine sulfate for advanced cancer had subjective improvements (patients reported an increase in appetite, a decrease in weight loss, an increase in strength, or a decrease in pain). Some patients had objective improvements (measurable tumor shrinkage, no further tumor growth, or improvement in a cancer-related disorder). Major weaknesses of the study included the lack of a comparison group (a group of patients who did not receive hydrazine sulfate) and the fact that half of the patients could not be evaluated for response to the treatment. Reasons that patients could not be evaluated included poor prognosis, missing information, short duration of treatment, and concurrent treatment with anticancer drugs (given at the same time as hydrazine sulfate).

From the 1970s to the mid 1990s, Russian scientists conducted a series of studies with hydrazine sulfate. The results of these studies were mixed. It is difficult to evaluate the scientists' findings because little information was provided about the patients and their treatment histories and about the study design and methodology. In addition, the studies lacked comparison groups (patients who did not receive hydrazine sulfate) and relied on subjective measures of quality of life (such as patient reports of improvements in appetite, weight stabilization or gain, or decrease in pain). All of the patients in these studies received previous or concurrent treatment with surgery, chemotherapy, and/or radiation therapy. Therefore, it is difficult to attribute any of the positive findings to treatment with hydrazine sulfate.

Three NCI-funded clinical series reported in the mid-to-late 1970s found that no patient treated with hydrazine sulfate had the tumor shrink significantly or disappear. In addition, only temporary minor improvements in appetite, pain, and weight stabilization or gain were reported by some patients. A problem in these 3 clinical series was the absence of control groups.

Findings from 4 controlled randomized clinical trials reported in the 1990s found that hydrazine sulfate was not effective in treating cancer. In some cases, it was actually harmful. (A randomized clinical trial is a study in which the participants are assigned by chance to separate groups to compare different treatments; neither the researchers nor the participants can choose which group.) One of these studies, which was sponsored by CALGB, found that patients with advanced lung cancer who received hydrazine sulfate in addition to a multidrug chemotherapy regimen experienced a significantly worse quality of life than patients who received a placebo (an inactive substance) in addition to chemotherapy. A second trial, sponsored by NCCTG, found that patients with colorectal cancer who received hydrazine sulfate had significantly shorter survival than patients who received a placebo. The remaining 2 trials compared hydrazine sulfate with a placebo in addition to a multidrug chemotherapy regimen for patients with lung cancer. Neither study found a difference in objective tumor response or improved survival in patients who took hydrazine sulfate. In one of the studies, patients who took hydrazine sulfate were judged to have better nutritional status than patients in the placebo group, although the increase in body weight was not significant.

Four other controlled randomized clinical trials that focused on the effects of hydrazine sulfate on nutritional or metabolic status found some objective evidence of benefit from hydrazine sulfate. In 2 of the studies, which were reported in the late 1980s, patients showed improvements in metabolism, appetite, and either weight increase or weight maintenance. In the other 2 clinical trials, reported in 1987 and 1995, hydrazine sulfate reduced the breakdown of body protein associated with cancer cachexia in patients with either lung or colon cancer.

7. Have any side effects or risks been reported from hydrazine sulfate?

In general, the side effects of hydrazine sulfate treatment have been described as mild to moderate in severity, and the frequency of side effects appears to have been low. Most side effects are reported to end when treatment with hydrazine sulfate is stopped. Limited evidence from animal studies, however, suggests that hydrazine sulfate may be highly toxic when combined with either alcohol or barbiturates (drugs with sedative and hypnotic effects).

Most of the side effects associated with hydrazine sulfate have involved the nervous system and gastrointestinal tract. These side effects have included nausea and/or vomiting, dizziness, abnormal sensations in the arms and legs (such as burning or prickling), nerve inflammation, and impaired fine motor function (such as difficulty writing). Other side effects have included dry skin and/or itching, insomnia, and abnormally low blood sugar. One case of fatal liver and kidney failure and one case of severe injury to the brain have been associated with the use of hydrazine sulfate.

8. Is hydrazine sulfate approved by the U.S. Food and Drug Administration (FDA) for use as a cancer treatment in the United States?

The FDA has not approved hydrazine sulfate for use as a cancer treatment in the United States (in other words, it has not been approved to be used in the treatment of cancer by licensed physicians). The FDA has only approved the study of hydrazine sulfate in clinical trials. At least 3 such clinical trials are known to have taken place in the past. At this time, however, NCI and the National Center for Complementary and Alternative Medicine (NCCAM) know of no such clinical trials under way. Hydrazine sulfate is commercially available in the United States as a dietary supplement.

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