From: Cancer Therapy
© 1992 by Ralph W. Moss, Ph.D.
Hydrazine sulfate is a common industrial chemical, which was used as a component of rocket fuel during World War II. It was Þrst proposed as a cancer treatment in the early 1970s by Joseph Gold, MD, of the Syracuse Cancer Research Institute, Syracuse, NY. Gold drew on the work of Nobel laureate Otto Warburg, who in the 1930s theorized that cancer derived its energy from anaerobic glycolysis (i.e., fermenting sugar) rather than respiring in the normal way. In 1968, Gold proposed using chemicals to control cancer's growth by exploiting this "Warburg effect."
In the early 1970s, Gold indicated that hydrazine sulfate could inhibit the growth of leukemia, lymphoma, melanoma and other cancers in rats (1, 2). He suggested that by cutting off a tumor¹s supply of "new glucose" in the liver, the drug could help starve the tumor. This, in turn, would stop cancer from preferentially depleting the body¹s energy pools and put an end to cachexia, the terrible wasting process that appears in the Þnal stages of the disease.
In fact, it is this wasting process that often kills the cancer patient. Some doctors believe that the answer to the weight loss in advanced cancer is to inject patients with all the nutrients they need through an intravenous drip. This is called total parenteral nutrition (TPN).
However, carefully controlled studies have shown "no signiÞcant improvement in either response or survival" associated with TPN for most kinds of cancer. In fact,
in two instances, TPN was associated with decreased survival (3).
Gold also showed that hydrazine sulfate could enhance the effect of such conventional drugs as Cytoxan, Mitomycin C, methotrexate and bleomycin in rats. He proposed that a "combination chemotherapy with hydrazine sulfate and a cytotoxic agent may be useful in the treatment of human cancer" (4).
Gold analyzed 84 terminally ill cancer patients who had been treated with hydrazine sulfate under a drug company¹s investigational new drug (IND) license. He found that 59 out of the 84, or 70 percent, improved subjectively while 14 out of the 84, or 17 percent, improved objectively. Subjective responses included increased appetite, weight gain or stoppage of weight loss, increased strength, improved performance status and decreased pain.
Objective responses included measurable tumor regression, disappearance of cancer-related medical problems and more than one year of stabilized condition. About
half of the people who responded had no other cancer therapy while they were receiving hydrazine sulfate. Some patients relapsed quickly; other remissions were long-term (5).
In Gold¹s 1975 study, the side effects were mild, consisting for the most part of a few incidents of tingling in the Þngers and toes, nausea, itching and drowsiness. There was no indication of bone marrow depression (5).
Hydrazine sulfate could be used alone or in combination with other drugs (6). In 1981, Gold showed that hydrazine sulfate treatment resulted in marked appetite improvement. In those patients receiving hydrazine sulfate alone, appetite improvement occurred in over 86 percent. In those who were also receiving conventional chemotherapy, it was almost 70 percent. Average weight gain for people receiving hydrazine sulfate alone was 8.2 lbs, while for those with other therapies it was only 0.6 lbs (7).
In the 1980s, Rowan Chlebowski, MD, PhD and colleagues at Harbor HospitalUCLA studied 38 patients with advanced cancer and weight loss. Patients were placed in a carefully-controlled study to evaluate the inþuence of hydrazine sulfate on carbohydrate metabolism. They were given a standard dose of 60 milligram capsules three times a day for 30 days. Glucose tolerance was much better in patients who received hydrazine sulfate than in those who received a placebo ("sugar pill").
Side effects of hydrazine sulfate were minimal. In one study, over 70 percent of the patients reporting no toxic effects (8). The UCLA team concluded that "hydrazine sulfate can inþuence the abnormal carbohydrate metabolism associated with weight loss in patients with cancer" (9).
Hydrazine sulfate was also evaluated in 101 heavily pretreated cancer patients who were suffering from weight loss. After one month, 83 percent of the hydrazine sulfate-treated patients, but only 53 percent of the controls, were able to maintain or increase their weight. In addition, UCLA scientists reported appetite improvement was more than twice as frequent in the hydrazine group. The hydrazine sulfate patients did not simply consume more calories, but utilized calories better than did the control patients (8).
Writing in the Lancet, UCLA researchers reported on 12 malnourished patients with lung cancer. They too received 60 milligrams three times a day for a month. There was less loss of the amino acid lysine in the hydrazine sulfate group than in those receiving the placebo. These too concluded that hydrazine sulfate reduced the "þux" of amino acids and could therefore favorably inþuence abnormalities in digestion among late-stage cancer patients (10).
In a larger study of lung cancer patients, the UCLA researchers reported on 65 patients with non-small-cell lung cancer which could not be operated on. All the patients received the same combination of standard chemotherapy (cisplatin, vinblastine and bleomycin) and the same dietary counseling. But patients who received hydrazine sulfate showed much greater intake of calories. Survival was somewhat greater in the hydrazine sulfate-treated group, especially those with less advanced cancers (11, 12).
A team of 11 scientists at the N.N. Petrov Research Institute of Oncology, Leningrad (St. Petersburg) have been working on hydrazine sulfate since the 1970s. The Russians have had the greatest single clinical experience with hydrazine sulfate, having treated and evaluated over 740 patients (13).
The patients were of many kinds, including 200 with lung cancer, 138 with stomach cancer, 66 with breast, 63 with Hodgkin¹s disease and 31 with melanoma. Patients were treated for one month at a time. If their disease became stabilized, there was an interruption of two to six weeks. Then they were treated again for a month.
Nearly half the patients had less cachexia while on the treatment: 14 percent had pronounced and 33 percent had moderate beneÞts. In addition, 10 percent showed tumor regression. All had disease stabilization.
Thus, in the Russian, as in the Syracuse and UCLA studies, hydrazine sulfate did something few other treatments could do: it inhibited the wasting process. The best results were seen with desmosarcoma, neuroblastoma, laryngeal cancer, Hodgkin¹s disease and breast cancer (13).
Later studies showed: hydrazine sulfate increased appetite, decreased pain, diminished anorexia, stabilized tumor growth and promoted survival. And it had few side effects (14).
Hydrazine sulfate is inexpensive and accessible. In most studies, the treatment regimen was three 60 milligram tablets each day for a month. Then patients stop for two to six weeks, and take another course as needed.
In the Russian studies, such courses were repeated two or three times. In some cases (especially neuroblastoma) there were 10, 20 or even 40 repeated courses. For cancer of the esophagus or larynx, the drug was administered as a 0.4 percent solution (in which 15 milliliters equalled one 60 milligram tablet). Barbiturates and alcohol are strictly prohibited during the administration of hydrazine sulfate. Hydrazine sulfate¹s use in cancer has always been controversial. After years of denigrating its use, NCI Þnally agreed to sponsor a phase III clinical trial at three medical centers. They are now under way.
See also The Cancer Chronicles article on hydrazine sulfate.
And check out the Web site of Dr. Gold's Syracuse Cancer Research Institute
which can be accessed through our Links page.
This site contains some of the full-text articles referenced below:
1. Gold J. Inhibition of Walker 256 intramuscular carcinoma in rats by administration of hydrazine sulfate. Oncology.1971;25:66-71.
2. 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. 1973; 27:69-80.
3. Chlebowski RT. Critical evaluation of the role of nutritional support with chemotherapy. Cancer.1985;55:268-72.
4. Gold J. Enhancement by hydrazine sulfate of antitumor effectiveness of cytoxan, mitomycin C, methotrexate and bleomycin, in Walker 256 carcinosarcoma in rats. Oncology.1975;31:44-53.
5. 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;32:1-10.
6. Gold J. Potentiation by cloÞbrate of in-vivo tumor inhibition by hydrazine sulfate and cytotoxic agents, in Walker 256 carcinosarcoma. Cancer Biochem Biophys.1978;3:41-5.
7. Gold J. Anabolic proÞles in late-stage cancer patients responsive to hydrazine sulfate. Nutr Cancer.1981;3:13-9.
8. Chlebowski RT, et al. Hydrazine sulfate in cancer patients with weight loss. A placebo-controlled clinical experience. Cancer.1987;59:406-10.
9. Chlebowski RT, et al. Inþuence of hydrazine sulfate on abnormal carbohydrate metabolism in cancer patients with weight loss. Cancer Res. 1984;44:857-61.
10. Tayek JA, et al. Effect of hydrazine sulphate on whole-body protein breakdown measured by 14C-lysine metabolism in lung cancer patients. Lancet.1987;2:241-4.
11. Chlebowski RT, et al. Hydrazine sulfate inþuence on nutritional status and survival in non-small-cell lung cancer. J Clin Oncol.1990;8:9-15.
12. Gold J. Hydrazine sulfate in non-small-cell lung cancer [letter; comment]. J Clin Oncol.1990;8:1117-8.
13. Filov V, et al. Results of clinical evaluation of hydrazine sulfate. Vopr Onkol. 1990;36:721-726.
14. Gold J. Hydrazine sulfate: a current perspective. Nutr Cancer. 1987;9:59-66.
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