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EFFICACY OF HYDRAZINE SULFATE IN THE TREATMENT OF HUMAN CANCER

Comprehensive Statement—August 1, 2013

In early April 2013 SCRI sent you its first official notice of the efficacy of hydrazine sulfate in the treatment of human cancer, dated April 2, 2013.

This notice described the controlled clinical trials of this drug performed from 1976 through 1990, in accordance with internationally ratified biomedical procedures (the Helsinki Declaration). These controlled studies included ten years of Phase III randomized, placebo-controlled, double-blind trials at Harbor-UCLA Cancer Center in Torrance, California and 17 years of multicenter Phase II equivalent trials headquartered at the N. N. Petrov Research Institute of Oncology in St. Petersburg, Russia. These positive trials were all published in premier American peer-reviewed medical journals.

The results of these controlled clinical studies showed:

(a) 50 percent measurable symptomatic improvement response. For every million late-stage, unresponsive cancer patients treated with hydrazine sulfate, a half-million would show sustained symptomatic improvement. (b) 40 percent tumor regression or stabilization for at least 3 months. (c) 5 to 10 percent long-term (> 10 years) “complete response” (survival).

Three controlled trials have failed to show positive effects. These trials were all sponsored by the National Cancer Institute. However, all three trials were in violation of the “generally accepted standards” rule, Principle 1, of the Helsinki Declaration by virtue of their use of incompatible agents (medications) with the test drug and therefore declared by this Declaration to have no scientific standing. Principle 1 of the Helsinki Declaration states: “Biomedical research involving human subjects must conform to generally accepted scientific principles and should be based on a thorough knowledge of the scientific literature.” (Incompatible agents constitute a “clinical hazard” capable of causing death.) The NCI-sponsored studies were also in violation of Principle 8 of the Helsinki Declaration, which states: “Reports of experimentation not in accordance with the principles laid down in this Declaration should not be accepted for publication.” Despite this, the NCI has consistently published the negative outcome of its sponsored trials of hydrazine sulfate, not only sequentially in the June 1994 issue of the Journal of Clinical Oncology (plus editorial) but also online annually.

The three NCI-sponsored studies are:

(a) Kosty MP, Fleishman SB, Herndon TE 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):1113-1120, 1994. (b) Loprinzi CL, Kuross SA, O’Fallon JR et al. Controlled Evaluation of Hydrazine Sulfate in Patients With Advanced Colorectal Cancer. J. Clin. Oncol. 12(6):1121-1125, 1994. (c) 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):1126-1129, 1994.

None of these studies carry the required published statement (as do other studies in conformity with the Helsinki Declaration): “This study was carried out in accordance with the Helsinki Declaration.”

Although SCRI sent almost 50 official notices of efficacy of hydrazine sulfate to major media sources and although the therapeutic results of the controlled clinical studies were spectacular and warranted a reply, SCRI did not receive a single response! Was there no media recipient interested in a cancer drug producing such dramatic clinical responses—50 percent measurable symptomatic response, 40 percent tumor regression or stabilization, 5-10 percent “complete response” all in advanced patients—especially under the circumstances of controlled clinical testing by major and respected cancer centers?

There is an explanation. In seeking to confirm the efficacy results of hydrazine sulfate contained in the SCRI notice of April 2, 2013, a media representative might well consult the nation’s first source of cancer information, the National Cancer Institute. This media representative would quickly learn of the NCI’s long standing adversarial position to hydrazine sulfate, to its developer, Dr. Joseph Gold, as well as to the SCRI.

To inquiries regarding the anticancer effect of hydrazine sulfate and how SCRI characterizes the clinical studies, NCI routinely replies:

“We interpret the [hydrazine sulfate] data differently from Dr. Gold.”

NCI goes on to explain that it does not consider the type of treatment effect produced by hydrazine sulfate as important as SCRI describes it. Whereas Dr. Gold thinks symptomatic improvement is important, NCI believes an anti-cancer effect is not significant until at least 50 percent tumor inhibition is achieved. At that stage, NCI stresses, the tumor itself—and the cancerous condition—is disappearing, not just does symptomatic improvement or tumor stabilization appear. The whole object of therapy is something permanent rather than evanescent.

Yet the hydrazine sulfate data are not a matter of “interpretation.” They are perfectly straightforward. They describe finite improvement of great patient value, such as diminution of pain and weakness characteristic of the pretreatment period, increased ambulation, ability to return to work, weight and appetite gain, loss of fever and effusions, normalization of the laboratory indexes, stabilizing effect on tumor growth, interruption of tumor progression and increased survival. These constitute therapeutic outcome factors of extraordinary value. They are not to be “traded in” for what has been described as a more “permanent” treatment effect, especially when each type of effect has its own type of benefit and especially when a permanent effect (“complete response”) can be an infrequent occurrence.

Carefully drawn NCI-sponsored studies failed to demonstrate any benefit for hydrazine sulfate. However, what NCI fails to specify is that all three sponsored studies were in violation of the Helsinki Declaration and declared by this Declaration to have no standing. No study carried the imprimatur of the Helsinki Declaration, as studies in conformity with the Helsinki Declaration require. These studies also failed to include as part of their informed consent forms the notation that hydrazine sulfate administered in conjunction with tranquilizers, barbiturates and alcohol constituted a “clinical hazard” capable of causing death. As a result patients who were part of these studies were not aware of the dangerous potential of these studies.

Moreover, because of pressure from the media alleging irregularities in the conduct of the NCI-sponsored hydrazine sulfate studies, in July 1994 the General Accounting Office (GAO),the investigative arm of Congress, began a Congress-mandated detailed investigation of these studies. After 10 months of intensive interviews with all the study heads and complete reviews of the data of all studies, the GAO found the NCI-sponsored studies of hydrazine sulfate to be totally accurate and thus NCI’s view of hydrazine sulfate correct. On September 15, 1995, the GAO published its official report: “Contrary to Allegation, NIH Hydrazine Sulfate Studies Were Not Flawed.”

However, it turned out there was a prior report. A 28-page Final Draft Report, predating the official report by three months, sharply criticized the NCI, constituting a scathing indictment of the validity of the NCI conclusions throughout the studies. The title of the Draft Report, dated June 5, 1995, was: “NIH Actions Spur Continued Controversy Over Hydrazine Sulfate Therapy.” The Report set forth: “NCI did not conduct adequate oversight of these trials. It did not take sufficient measures to appropriately address concerns over alleged incompatible agents. FDA also acted inconsistently in its oversight role with regard to this drug being administered to patients. Lastly, the issue of possible incompatibility of hydrazine sulfate with certain other agents is unsettled.”

According to an investigative report (Jeff Kamen, Intent to Kill, Penthouse, September 1998) within two days of receiving the Final Draft Report from the GAO, NCI officials “screamed” for changes. Within a week the GAO was hit with a “blistering memo” demanding a major rewrite.

In swift succession, 30-year veteran GAO investigator Barry D. Tice, Assistant Director of GAO’s Health Division and writer of the Final Draft Report, was dismissed as lead investigator of the GAO investigation and his deputy in training, Gloria Taylor, was appointed to replace him.

Shortly afterward the GAO sent notices to all agencies to whom it transmitted the Final Draft Report for review, that the Final Draft Report was to be “embargoed” and not made public, that all copies were to be returned to the GAO immediately. However, Senator Theodore Stevens of Alaska and Congressman Robert G. Torricelli of New Jersey independently thought it was in interest of the American people to know of the Final Draft Report and made it available immediately to the media. Other Congressmen followed suit and took similar action.

Respected consultant biostatistician Richard D. Wilkins submitted a 19-page statistical analysis of the NCI-sponsored studies of hydrazine sulfate and specifically of nine retrospective analyses presented by the NCI to the GAO by which the NCI attempted to show that the use of tranquilizers, barbiturates and alcohol had no effect on hydrazine sulfate action or study outcome. Wilkins reported: “The NCI retrospective analyses, as presented [to the GAO] cannot statistically substantiate any claim that use of adjunctive tranquilizers and/or barbiturates had no (deleterious) effect on hydrazine sulfate drug action or on survival outcome.” Jeffrey S. Robbins, Chief Counsel of the Senate Permanent Subcommittee on Investigations, in an inquiry on the NCI studies and GAO investigation, added: “The NCI studies are flawed to the point of being meaningless…The American people didn’t get what they paid for: an unbiased test of the drug and an unbiased report on the conduct of the NCI.”

A representative of the media contemplating a story based on the SCRI report of hydrazine sulfate would not only quickly learn that the NCI’s “interpretation” of significant anti-cancer action means “objective response,” i.e., 50 percent tumor regression or greater vs. SCRI’s or Dr. Gold’s opinion being the weaker “symptomatic improvement” or “stabilization.” Yet it would be worse than that. The media representative would be informed unrestrictedly of the NCI’s three large-scale, nationwide, thorough, sponsored studies taking place in hospitals throughout the country showing that hydrazine sulfate has no anti-cancer action whatsoever—neither symptomatic or antitumor. One cannot be serious about mounting a nationwide media story on the anti-cancer potential of hydrazine sulfate. It has none!

After learning that NCI holds hydrazine sulfate to much stricter “interpretations” (standards) of anti-cancer actions; has engaged in three large-scale detailed studies showing hydrazine sulfate to have no anti-cancer action at all; and even is able to present “proof”—a GAO investigation—that there was nothing “wrong” with these studies, our NCI spokesman might then summarize to our media representative:

“Why would you want to give false hope to hundreds of thousands of people?”

Why indeed?

Actually, the SCRI announcement was corroborated in all its views of efficacy of hydrazine sulfate—by the very evidence presented to our media representative by his NCI informant:

(a) The NCI’s standard of anti-cancer action is “objective response,” a minimum of 50 percent tumor regression or greater—in contrast to the SCRI’s “weaker” symptomatic benefit or tumor stabilization or regression. But the SCRI announcement also included 5 percent – 10 percent long-term (> 10 years) survival, which is “objective response,” i.e., 100 percent tumor regression. Equally important, many of the patients achieving symptomatic improvement or stabilization in the Petrov studies—especially those with lymphoma, desmosarcoma, neuroblastoma and others—are indicated as having done so long-term, some for “years,” as a result of multi-course therapy. This long-term response can constitute the equivalent of total remission. NCI has only recently indicated that stabilization for even one month can be valuable to the patient and has named this a treatment goal.

(b) The NCI sponsored three large-scale, multi-center controlled studies which showed hydrazine sulfate to have no anti-cancer effect; one study had to be terminated early because of increased numbers of patient deaths (presumably due to hydrazine sulfate). However, the conclusions reached in all NCI-sponsored studies were invalidated due to these studies’ violation of the Helsinki Declaration. Such studies are commonly regarded in the scientific community as de-legitimate, frequently the equivalent of bogus.

In the colorectal study terminated early because of increased patient deaths, these deaths may not have occurred had NCI taken seriously the animal data it had received long before the start of its sponsored studies and/or had taken the simple precaution of including in the patient consent forms the notation that hydrazine sulfate administered in conjunction with tranquilizers, barbiturates or alcohol could constitute a “clinical hazard” that could cause death. The data received by the NCI showed that animals (rats) given the standard dosage of hydrazine sulfate suffered no untoward effects; animals given tranquilizers in standard doses became sleepy for a few hours, but recovered; animals given the two together suffered a 20 percent death rate and 60 percent more became comatose for 24 hours or longer. It was in the third arm of this study of very sick, advanced, weakened colorectal cancer patients (who had all failed prior 5 fluorouracil-based chemotherapy for entry into the study) in whom the increased deaths occurred, mimicking exactly the animal data received by NCI long prior to its studies.

(c) A General Accounting Office (GAO) investigation of the NCI-sponsored studies showed these studies to be carried out correctly and to be without flaw. However, this turned out not to be the case. A prior 28-page Final Draft Report of this investigation was published three months earlier which scathingly criticized the NCI-sponsored studies, calling them incorrect and fatally flawed. The officially published GAO report was seen to be the result of a mandated rewrite emanating from higher government levels.

Thus much of what our media representative might have learned from his NCI informant might have been the result of what have been termed “phony” or “bogus” studies (studies in violation of the Helsinki Declaration) or a “political fix” of a Congressionally ordered investigation.

But a media person would not suspect—in a practical sense, would have no way of knowing—that the information given him by the NCI was not legitimate. That the studies by which hydrazine sulfate were being shown to have no anti-cancer activity were in violation of an internationally ratified Declaration governing allowable procedures that can be used in human biomedical research studies—and were thus totally devoid of scientific validity. That a GAO—“government”—investigation of these studies showed them to be correct, when actually the opposite was shown to be the case.

There is another source of hydrazine sulfate information. It is called Sehydrin. It is the trade name of the drug hydrazine sulfate, produced by the pharmaceutical company Pharmsynthez. It is the only pharmaceutical company—located in St. Petersburg. Russia—that produces hydrazine sulfate in the world. Currently the drug is registered and marketed in the former countries of the Soviet Union, the Balkans, Germany, Canada and reportedly plans are being formulated for marketing in further countries, including the possibility of the United States. (The SCRI nor anyone associated with it maintains no connection with Pharmsynthez and does not participate financially or in any way in Sehydrin sales or distribution.)

The clinical results of Sehydrin are virtually identical to those described in SCRI’s April 2, 2013 announcement of the efficacy of hydrazine sulfate in human cancer—marked symptomatic improvement in 50 percent of patients, tumor stabilization and regression for three months or longer, long term survival (“complete response”) in 5 percent to 10 percent of patients. Pharmsynthez on its website emphasizes that the main effect of Sehydrin is “palliative” (symptomatic improvement, stabilization)—“which is developed in 45.6% - 70% of patients with different cancers”—resulting in: “increased appetite and weight, decreased hemoptysis and respiratory insufficiency [in lung cancer patients], decrease in edema and effusions, improved overall health, easing of depression, a feeling of well-being sometimes bordering on euphoria, increased vigor and physical activity, decreased fatigue and anorexia, reduction in or complete elimination of pain (allowing the reduction or discontinuation of the use of analgesics).” Also noted: “A statistically significant increase in the duration of remission was observed in the treatment of breast cancer, brain tumors, lung cancer.”

The Ukrainian company GFMG, a pharmaceutical business located in Kiev, reports (on its website): “Ukrainian families have for a long time lived in painful heartfelt tension because of their heavy fate to be relatives of cancer patients. At home cancer patients suffer from frightful pain because such patients are usually discharged from the hospital. Such patients are a heavy burden for hospital staffs who are under the obligation to help, but the opportunity to help is almost absent. However, nowadays an opportunity has appeared. In the Ukraine a preparation [pharmaceutical] has been registered for palliative help for cancer patients, which improves life quality unprecedentedly in even the most terminal patient – it is called Sehydrin!”

GFMG enumerates the anti-cancer actions of Sehydrin:

  • decreases or eliminates pain up to the abandonment of narcotics and analgesics
  • reduces fever, normalizes temperature
  • reduces hemoptysis, respiratory insufficiency, edema
  • normalizes laboratory indexes
  • increases appetite and reduces intensive weight loss
  • considerably improves general well-being, promotes physical activity and promotes the mood

The Sehydrin experience thus corroborates and confirms the SCRI April 2, 2013 announcement of the efficacy of hydrazine sulfate in cancer patients. As independent confirmation of the SCRI announcement, no stronger scientific evidence can attest as to the scientific correctness of this announcement. There can be no doubt that the described therapeutic effects of hydrazine sulfate are real or of the potential applicability of their anti-cancer effects to hundreds of thousands, if not millions, of people.

But this drug is being used by only very few patients at present. Only because its efficacy is being denied to the medical profession and to the lay public alike, principally by the most influential, and largest, cancer agency in the world, the U.S. National Cancer Institute.

News of the efficacy of hydrazine sulfate and its applicability to cancer patients must have a way of reaching all cancer patient populations wherever they may be if its therapeutic potential is to be realized.

I urge those media representatives who may be interested in formulating a story after reading this statement—in liberating this pharmaceutical from the cage it is now in and so to give hundreds of thousands, if not more, people some hope of obtaining remission from their disease—to consult the medical literature directly to verify for themselves the correctness of this statement. In general published studies are not difficult to understand. They contain straightforward language and pronouncements. Pronouncements like these: “Interruption of tumor progression during the administration of Sehydrin for a period of more than 3 months was observed in 216 out of 740 patients (29.2%)....Stabilization was observed in a total of 35.5% of patients” (Filov VA et al. Experience of the treatment with Sehydrin [Hydrazine Sulfate, HS] in the advanced cancer patients. Invest. New Drugs 13: 89-97, 1995). “Hydrazine sulfate compared with placebo addition to chemotherapy resulted in significantly greater caloric intake and albumin maintenance [and] significantly prolonged survival....The prospect that cancer patient survival may be increased by improving host metabolism represents a fundamentally new direction for clinical cancer management” (Chlebowski RT et al. Hydrazine Sulfate Influence on Nutritional Status and Survival in Non-Small-Cell Lung Cancer. J. Clin. Oncol. 8: 9-15, 1990).

There are 11 positive controlled studies that majorly reference the efficacy and safety of hydrazine sulfate. These are enumerated on SCRI’s website: scri.ngen.com. To reference each study, once on the SCRI website, please click on “articles.” This will present a listing of the controlled studies. On the left of the title of each study is an icon. Clicking on the icon will present the “abstract” (summary) of the study. Clicking on the right—on the title itself—will present the entire full-length study. The abstract and the full length study will be presented exactly as they appear in the medical journal. There will be no additions, commentary or article alterations. The NCI-sponsored studies, referenced on pages 1 and 2 of this statement, do not appear on the SCRI website, since their content and conclusions are uncertain (open to doubt) due to their violation of Helsinki Declaration. It is important to note that although these studies appear professional and thorough, they are out of compliance with allowable, internationally accepted standards and principles which govern how a study may be carried out.

Joseph Gold, M.D.

 


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