Hydrazine sulfate

== Hydrazine Sulfate == (trade name Hydrazine Sulfate, Sehydrin)

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Hydrazine sulfate is a gluconeogenic blocking agent irreversibly inhibiting the enzyme phosphoenolpyruvate carboxykinase (PEP CK), and is used in the treatment of cancer cachexia,[1] the weight loss and debilitation seen usually in late-stage cancer, which accounts for upwards of 50 percent of all cancer deaths. It was the first clinical agent developed specifically for the treatment of cancer cachexia.

Hydrazine sulfate is currently available in the United States by a doctor’s prescription filled in a compounding pharmacy. No pharmaceutical company has ever submitted a New Drug Application (NDA) to the United States federal Food and Drug Administration (FDA); consequently an NDA for this drug has never been approved or disapproved by the FDA.

Hydrazine sulfate has been reported to be used in most types of cancer, at all stages, and indicated to be effective by itself, in conjunction with chemotherapy and radiation therapy and with other modalities of cancer treatment.

Background

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Hydrazine sulfate was specifically developed as a result of a theoretical paper by Joseph Gold, M.D., indicating cancer glycolysis and normal-body gluconeogenesis to constitute a systemic (whole-body) energy-losing cycle as the biochemical and thermodynamic cause of cancer cachexia and postulating the inhibition of gluconeogenesis at the enzymic site of PEP CK to be an effective treatment for cancer cachexia. It was also postulated that if tumor energy gain (glycolysis) and host-energy loss (gluconeogenesis) were functionally interrelated, inhibition of gluconeogenesis at PEP CK could result in actual tumor regression in addition to reversal or arrest of cancer cachexia.

Indications

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Although no NDA has ever been submitted to the FDA for hydrazine sulfate, controlled clinical studies have indicated the utility of this drug in a number of different kinds of cancer, including Hodgkin’s and non-Hodgkin’s lymphoma, lung cancer, breast cancer, neurological cancer, colorectal cancer, head and neck cancer, vulvar, cervical, endometrial and ovarian cancer, sarcomas, recurrent desmoid tumors and others.

Investigational

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Controlled clinical trials, performed in conformity with the Helsinki Declaration, indicated efficacy and safety in about 50 percent of all patients. Efficacy and safety were expressed in terms of appetite and weight improvements, performance status increase, decrease or disappearance of pain and weakness, tumor stabilization and regression and increased survival time. These multicentric Phase II and randomized, double-blind Phase III clinical trials were carried out at the Petrov Research Institute of Oncology in St. Petersburg (with the participation of the Herzen Institute of Oncology, Moscow, Oncological Institute of Lithuania, Vilnius, Institute of Oncology of the Ukrainian Academy of Sciences, Kiev, and Rostov Institute of Oncology and Radiology, Rostov an Donau) over a period of 17 years—and at the Harbor-UCLA Medical Center in California over period of 10 years, respectively. Studies were published chiefly in U.S. peer-reviewed, well known journals.

(The Helsinki Declaration—an outgrowth of the Nuremberg trials [Doctors Trial] following World War II which uncovered the heinous medical “experiments” inflicted by the Nazis on helpless human beings—is a multinational ratification of principles governing human biomedical research studies, to which the United States is a signatory, put in place to guarantee that no harmful procedures be used in patients undergoing experimental medical treatment. This Document is central to all clinical studies and informed consent and represents the international “law of the land,” requiring all human biomedical research to conform to its stated principles.)

Hydrazine sulfate was found to be non-effective in three randomized clinical trials sponsored by the U.S. National Cancer Institute (NCI). These NCI-sponsored studies, however, were said to be in violation of the “generally accepted standards” rule of the Helsinki Declaration, by virtue of their use of incompatible agents (medications) in the presence of a test drug. Principle 1 of the Helsinki Declaration states: “Biomedical research involving human subjects must conform to generally accepted scientific principles…and be based on a thorough knowledge of the scientific literature.” Incompatible medication in the presence of a test drug is virtually unknown in human biomedical testing, since it can result in the grave illness—or death—of a patient and can result in a negative drug study.

By order of Congress, an investigation of the NCI-sponsored studies of hydrazine sulfate was undertaken by the General Accounting Office (GAO), the investigative arm of Congress. After 14 months of investigation, the GAO issued a 28-page Final Draft Report highly critical of the NCI-sponsored studies (“N.I.H. Actions Spur Continued Controversy Over Hydrazine Sulfate Therapy”), which included the following statements: “NCI did not conduct adequate oversight of these trials. It did not take sufficient measures to appropriately address concerns over alleged incompatible agents. The issue of possible incompatibility of hydrazine sulfate with certain other agents remains unsettled.” This report was circulated as a routine courtesy to the Food and Drug Administration, the Public Health Service, the NCI and certain Congressional committees, for any comments prior to publication. According to an investigative report,[16] within days of receipt of this draft report, the NCI demanded changes, the lead investigator was dismissed and a new and official GAO report was shortly thereafter prepared and issued to Congress and to the public, totally exonerating the NCI-sponsored studies of any deficiencies or flaws.