Wednesday, February 20, 2008

A dog has a better chance of recovering from cancer than you do...

You're being hoodwinked on hydrazine sulfate. As many of you already know from our previous blogs (published and accessible on this Web site), hydrazine sulfate is an inexpensive cancer drug that acts to reverse weight loss and halt tumor growth. The National Cancer Institute (NCI)--part of our federal government--says that hydrazine sulfate is worthless. But the facts are that a dog has a better chance of recovering from cancer than you do.

Previous studies--done properly--show that hydrazine sulfate is effective and safe in large numbers of cancer patients with all types of cancer and at all stages, interacts well with other types of cancer therapies and is free of harmful clinical side effects. Previous studies--done improperly--i.e., the NCI's sponsored studies of this drug--show that hydrazine sulfate is ineffective. NCI's "good word" is out to physicians (in cancer journals) and lay people (on the Internet) that hydrazine sulfate is no good. But NCI's message has not yet reached veterinarians and animal caregivers. Consequently many animal health care professinals are now using hydrazine sulfate on small animals--pets--with cancer. And the reported results are that many dogs and cats with advanced solid cancers are recovering, frequently fully, from their disease. A dog stands a better chance of getting this drug and thus recovering from cancer than you do.

How did this situation arise?

The underlying question here is, Is the anticancer action of this drug real? Does it really work? Or is it a figment of its developer's--Dr. Gold's--imagination? His wishful thinking?

In deciding whether a drug is active or not, one should never take the word of an individual--the drug's developer or its critics--no matter how authoritative that individual/those individuals might be. It is only the studies that will answer this very basic question. And there are only two aspects to all studies that must be considered: their quality and whether they are properly--in accordance with established and accepted scientific priniciples of study conduct--done.

As indicated, you must be very careful not to take the word of any individual--no matter how prestigious or authoritative--that hydrazine sulfate is effective or not effective. Specifically, the adversaries of hydrazine sulfate--many of them respected, authoritative cancer officials--like to say, "Dr. Gold claims..." and then recite a litany of benefits, or the like--and thus diminish the situation by "personalizing" it. It is as though there is no scientific backing to Dr. Gold's remarks. Actually, Dr. Gold doesn't "claim" anything--and never has. It is the studies. Dr. Gold is simply relating the results of studies--controlled clinical trials performed according to internationally established and accepted scientific criteria.

What are these studies? There are two sets of studies demonstrating the efficacy and safety of hydrazine sulfate. The first were seventeen years of Phase-II controlled, multi-institutional clinical trials headquartered at the Petrov Research Institute of Oncology, St. Petersburg (with participation by the Herzen Institute of Oncology, Moscow; Oncological Institute of Lithuania, Vilnius; Institute of Oncology of the Ukranian Academy of Sciences, Kiev; and Rostov Institute of Oncology and Radiology, Rostov-an-Donou). The second were ten years of randomized, controlled clinical trials--'RCT's (the "gold-standard" of clinical trials)--performed at Harbor-UCLA Cancer Center in Los Angeles. These studies showed that of every million late-stage, refractory cancer patients treated with hydrazine sulfate, more than half a million would obtain measurable symptomatic improvement, 400,000 would demonstrate a halt or regression in tumor growth, and some would go on to long term (>10 years) survival. (More than 500,000 Americans die each year from cancer, and more than one million new cases are reported annually in the U.S. alone.)

Who are the authors of these studies? Where were they published? The authors of these studies were among the leading and most experienced cancer investigators the world over. Among the Harbor-UCLA investigators were a former senior official at the NCI, with specific expertise in the implementation and evaluation of new clinical trials and a cancer scientist renowned in the field of intermediary cancer metabolism, entrusted by the U.S. government to help establish a cancer teaching center in Taipei, Taiwan, the Republic of China. Among the Petrov Institute investigators , Dr. M. L. Gershanovich, chief of studies and deputy director of the Russian equivalent of the U.S. Food and Drug Administration, was regarded by our NCI as one of the principal chemotherapists of the world. These studies were published in such peer-reviewed American journals as Cancer Research, Journal of Clinical Oncology, Cancer, The Lancet, Investigational New Drugs, and others, considered among the most respected, 'premiere' clinical cancer and scientific journals in the world.

Did these studies conform to the Helsinki Declaration? The Helsinki Declaration is a multinational ratification of principles governing human biomedical research studies, first adopted by the World Medical Assembly in Helsinki, Finland, June 1964, and thereupon amended by this organization in 1975, 1983 and 1989. An outgrowth of the Nuremberg Trials (Doctors Trial) following World War II which uncovered in detail the hideous human medical "experiments" inflicted on helpless human beings by the Nazis, the Declaration, to which the United States is a principal signatory, was put in place to guarantee that no harmful procedures be used in patients undergoing experimental medical treatment. This document lies at the very heart of internationally accepted standards for biomedical research and is at the very core of all clinical trials and informed consent. As such, the Helsinki Declaration represents the international "law of the land" and requires all human biomedical research to conform to its stated principles.

The Russian (Petrov Institute) and Harbor-UCLA studies of hydrazine sulfate were in full conformity to the Helsinki Declaration.

Are the two sets of studies--the Russian and Harbor-UCLA--connected? There is no link, no connection whatsoever between the two sets of studies. As such they constitute independent confirmation of one-another. This is the strongest kind of confirmation known to science and acts to confirm and strengthen the validity of each other's conclusions.

You must decide: What is the likelihood of these studies being authentic? That the results demonstrated--that hydrazine sulfate is effective and safe in a broad spectrum of cancers--are real, credible?

Now let us look at the NCI-sponsored studies--the ones which indicate hydrazine sulfate to be worthless. There were three such studies, all lasting less than two years. One of these--the largest--was conducted under the auspices of the Scripps Clinic in La Jolla, California, the other two by the Mayo Clinic in Rochester, Minnesota. All three were randomized, controlled clinical trials.

Who were the authors of these studies? Where were they published? The lead investigator of the largest of the three studies--the Scripps Clinic study--was still concluding his two-year military obligation in the U.S. Navy when designated by the NCI as principal investigator of this study. He was totally inexperienced in conducting a clinical study of any kind, and by his own words in a published interview he was quoted as stating he had "never held the reins of a major study before." The NCI was aware that the conduct and outcome of this study had the potential of impacting the lives of millions of cancer patients around the world. The lead investigator for both the second and third studies, although young, was not inexperienced in the conduct of clinical trials. Appointed as principal investigator of these studies by the NCI, he found himself in an instant, ethically compromizing situation. For as principal investigator of the two NCI-sponsored studies of hydrazine sulfatge, he was also--at the same time--the principal investigator of a study of a competing, private-sector drug, Megace, from Bristol-Myers Squibb Company, of which he was an outspoken advocate and in which Bristol-Myers Squibb had large proprietary interests. Entrusting two pivotal studies of competing drugs to the same principal investigator at the same time--one in which a large pharmaceutical company had sizable financial interests--inevitably raises the spectre of conflict of interest. Health policy analyst Lynn H. Ehrle writes: "Dr. [L....] was the principal investigator of the anti-cachexia drug, Megace, and his selection by the NCI to conduct two trials of hydrazine sulfate is a clear conflict of interest." Referencing the principal investigator's experience in the conduct of clinical trials, Ehrle states: "He should have recused himself." (Letter to Randy P. Juhl, Chair, FDA Pharmacy Compounding Advisory Committee, November 3, 1999.)

The three NCI-sponsored studies were published in the Journal of Clinical Oncology. But these studies were not the usual types of publication, submitted for outside, independent (external) peer-review and then individually published as these studies were completed. These studies were "arranged" for publication. Although they were completed at far different intervals of time, they were published sequentially as lead articles in the same issue (June 1994) of this journal. This could not have happened without prior collaboration between the authors and the journal, leaving open the question as to whether these studies were "juried" in the usual manner. The effect of sequential publication is to emphasize their findings. The NCI was not satisfied to emphasize their findngs. They sought also to dramatize them. A fourth "study" was also published in this same journal issue--a lead editorial, in which hydrazine sulfate was identified as a "vampire" and the three NCI studies as "three stakes" in the heart of the vampire ("Three Stakes in Hydrazine Sulfates' Heart..."). Thus the publication of these studies is not entirely normal, is irregular by virtue of prior "arrangement"--i.e., lack of separation--between authors and journal and use of improper and biased language. (Study results were also published by the NCI electronically [on the Internet].)

Did the NCI studies conform to the Helsinki Declaration? The paramount principle--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." Perhaps most important of generally accepted scientific principles in the conduct of human biomedical research is that no incompatible agents (medications) be used in a drug trial. Why? Because such use can result in the grave illness--or death--of a patient, as well as cause a negative drug study. For this reason use of an incompatible agent--or one even suspected of incompatibility--is virtually unknown in human biomedical testing.

But the NCI used incompatible agents in all its sponsored studies of hydrazine sulfate. Hydrazine sulfate belongs to a class of drugs known as MAO--monoamine oxidase--inhibitors and was indicated in pharmacology textbooks for three decades prior to the NCI-sponsored studies as an "irreversible," i.e., powerful, MAO inhibitor, and throughout the scientific literature as a mitochondrial MAO inhibitor. Also indicated throughout the scientific literature were multiple warnings that use of tranquilizers, barbiturates and/or alcohol with an MAO inhibitor constituted a "clinical hazard." But these were the very substances NCI elected to use in its hydrazine sulfate trials. (One of NCI's studies was terminated early because of unexpected illnesses and death.)

Principle 8 of the Helsinki Declaration states: "Reports of experimentation not in accordance with the principles laid down in this Declaration should not be accepted for publication." This principle essentailly states that the NCI-sponsored studies of hydrazine sulfate, out of compliance with the major principle of this document (Principle 1), should never have been presented (or accepted) for publication--no less "arranged" for sequential publication or appearance in the electronic media.

The NCI-sponsored studies of hydrazine sulfate were out of compliance with the Helsinki Declaration.

Thus, the Petrov Institute and Harbor-UCLA studies were carried out by experienced investigators, acknowledged by their peers to be among the foremost cancer investigators and chemotherapists in the world and entrusted by their respective governments to high positions of responsibility in their cancer programs. These studies were individually subject to outside, independent peer-review before winning publication in journals considered among the most leading and respected internationally. The Petrov Institute and Harbor-UCLA studies were not "connected" in any way and as such constituted independent confirmation of one-another, reinforcing the validity of their individual data. These studies were in full compliance with the Helsinki Declaration. There were no "irregularities" or conflicts of interest in either set of studies. These studies represent straightforward investigations--impartial, objective, unbiased--carried out in strict accordance with internationally established and recognized principles and criteria.

In contrast, the largest of the NCI studies was carried out by an individual totally inexperienced in the conduct of clinical trials, still serving his required military obligtion in the U.S. Navy when appointed by the NCI as principal investigator of this study. By his own words, he had "never held the reins of a major study before." The principal investigator of both the second and third NCI studies, in assuming leadership of these clinical trials, immersed himself and the studies in an immediate--and major--conflict of interest. For as principal investigator of the NCI-sponsored studies of hydrazine sulfate, he was also--at the same time--the principal investigator of a study of a competing drug from the private sector, of which he was an outspoken advocate and in which a large pharmaceutical company had very sizable financial interests. These studies were "arranged" publications--it is not clear whether they were subject to outside, independent peer-review--and appeared sequentially in the same journal issue, denoting prior interaction--collaboration--between authors and journal. All three NCI studies were "interconnected" and not independent of each other (one author was principal investigator of two of the studies)--there was no independent confirmation of any of these studies. The studies did not conform to the Helsinki Declaration. The drug under study was referred to as a "vampire" ("Three Stakes in Hydrazine Sulfate's Heart...") by an accompanying NCI editorial in the same journal issue as the three NCI-sponsored studies, leaving open the question as to their 'legitimacy' as impartial, objective scientific investigations.

Who--which studies--would you stake your life on?

If you or a family member or a loved one or a friend or neighbor had cancer--and you wished to have a trial on hydrazine sulfate--you may have to answer this question. The chances are your doctor has never heard of the Petrov Institute or Harbor-UCLA studies. He/she has only heard of the widely publicized NCI studies and will tell you, in good faith, that hydrazine sulfate is ineffective. Your doctor has heard countless times the following NCI advice regarding hydrazine sulfate, which NCI has posted annually for the medical profession and the public alike. and appears currently, on the Internet:

"There is only limited evidence from animal studies [i.e., no human studies] that hydrazine sulfate has anticancer activity."

"Hydrazine sulfate has shown no anticancer activity in randomized clinical trials [the "gold-standard" of clinical trials]."

How can your doctor fail to believe these statements from the NCI, perhaps the most respected cancer authority in the world, that only animal--no human--studies, certainly no randomized clinical trials, have shown any anticancer activity of hydrazine sulfate?

Chlebowski RT, Heber D, Richardson B and Block JB. Influence of Hydrazine Sulfate on Abnormal Carbohydrate Metabolism on Cancer Patients with Weight Loss. Cancer Research 1984; 44:857-861.

Tayek JA, Heber D and Chlebowski RT. Effect of Hydrazine Sulphate on Whole-Body Protein Breakdown Measured by 14C-Lysine Metabolism in Lung Cancer Patients. The Lancet 1987; 2:241-243.

Chlebowski RT, Bulcavage L, Grosvenor M, et al. Hydrazine Sulfate in Cancer Patients with Weight Loss. Cancer 1987; 59:406-410.

Chlebowski RT, Bulcavage L, Grosvenor M, et al. Hydrazine Sulfate Influence on Nutritional Status and Survival in Non-Small-Cell Lung Cancer. Journal of Clinical Oncology 1990; 8:9-l5.

No human studies done? The above represent 4 of the 15 human studies done since 1975. No randomized clinical trials? All the above are randomized clinical trials. No anticancer activity? All the above, all human studies, demonstrate anticancer activity. ("Hydrazine sulfate resulted in tumor stabilization and regression in 71% of 38 patients with [brain cancer]....Hydrazine sulfate prolongs patient survival and improves quality of life in this category of cancer patients." "Treatment with hydrazine sulfate resulted in complete tumor regression in 6 of 740 (0.8%) of patients, partial tumor regression in 25 (3.4%) of patients, up to 25% tumor regression in 47 (6.4%) of patients, tumor stabilization in an additional 263 (35.5%) patients and accompanying symptomatic improvements in 344 (46.5%) of the patients." "Using a randomized, placebo-controlled study design...hydrazine sulfate treatment resulted in significant improvement in the abnormal glucose metabolism seen in patients with weight loss and cancer." "The proposal that cancer patient survival may be increased by improving host metabolism represents a fundamentally new direction in cancer management.")

Your doctor, however, has no reason to doubt the veracity of the NCI statements regarding hydrazine sulfate--and that's the problem. The medical profession is largely uninformed that a substantial medical and scientific literature exists--including the above--which demonstrates the efficacy and safety of hydrazine sulfate in cancer.

If you want a trial on hydrazine sulfate--and it is perfectly legal for your doctor to write you a prescription for this drug--you will have to inform him/her of the Petrov/Harbor-UCLA studies. Your doctor will simply have to learn that the NCI studies were intrinsically flawed, not performed in conformity to the Helsinki Declaration, and that NCI advice regarding hydrazine sulfate--is simply wrong.

Most professional animal caregivers--veterinarians and others--are not in the mainstream of NCI disseminations and thus are 'immune' to NCI advice regarding hydrazine sulfate. Moreover, these individuals seem to be willing to go the extra mile for their patients--the dogs and cats who are unable to speak for themselves and thus have no other advocate for them. So these dogs and cats more easily have a try on hydrazine sulfate, when their owners present these caregivers with authentic medical evidence showing efficacy and safety of hydrazine sulfate in cancer. Thus "a dog has a better chance of recovering from cancer than you do...."

But this need not be the case. You can have the same chance as these cherished animals. But you must first present your doctor with the same evidence that pet owners present to their animal caregivers. You must present them with evidence that controlled clinical trials, properly done, including randomized clinical trials, have demonstrated the effectiveness and lack of serious side effects of hydrazine sulfate in various types and at all stages of cancer. You must also present them with evidence that the NCI-sponsored studies were performed out of conformity to the Helsinki Declaration and that NCI advice regarding hydrazine sulfate is misleading and misrepresents the medical literature.

I suggest you bring a copy of this blog to your doctor, if you are interested in obtaining a trial on hydrazine sulfate for yourself or family member or friend and informing the doctor of an Internet Web site on which the actual Petrov/Harbor-UCLA published studies are available as published--i.e., without added commentary ( Your doctor can then judge the quality of these studies and make an informed judgment as to whether a trial on hydrazine sulfate may be warranted and/or useful.

But there is something else you can do.

Send a copy of this blog to any friend, any acquaintance, you might have who has cancer--or whose friend or acquaintance or family member has cancer. Send a copy of this blog to your doctor. To your health care provider. To the earnest people in hospice who care for human beings in their last weeks and months of life. Send a copy to your congressman or congresswoman. Ask them to do something about this tragic situation which keeps really ill people from a drug which competently performed clinical studies say might help them and only incompetently performed clinical studies say otherwise.

We must do something to elevate our chances of survival from a dread disease to those our cherished animals currently enjoy.