[24] – 1995 (10/27/1995) – Burzynski to Dr. Richard Klausner (7 pgs.)

This page is linked to:
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Critiquing: Dr. Michael A. Friedman, Dr. Mark G. Malkin, Dr. Mario Sznol, Robert B. Lanman, Memorial Sloan-Kettering Cancer Center, Mayo Clinic, Department of Health & Human Services (HHS), Public Health Service, Quality Assurance and Compliance Section, Regulatory Affairs Branch (RAB), Cancer Therapy Evaluation Program (CTEP), Division of Cancer Treatment (DCT), National Cancer Center (NCI) at the National Institutes of Health (NIH), Stanislaw Burzynski: On the arrogance of ignorance about cancer and targeted therapies
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https://stanislawrajmundburzynski.wordpress.com/2013/09/08/critiquing-stanislaw-burzynski-on-the-arrogance-of-ignorance-about-cancer-and-targeted-therapies/
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[24] – 1995 (10/27/1995) – Burzynski 7 page letter to Richard Klausner, M.D., Director, National Cancer Institute (NCI), National Institutes of Health (NIH)

I was shocked to read the Cancernet “fact sheet” the NCI has been distributing about the cancellation of the clinical trials of antineoplastons, the anti-cancer drugs I discovered and developed

I find it scandalous that a government agency is putting out a public document containing such blatantly false information

Let me remind you that the only reason the clinical trials of antineoplastons were stopped is that NCI would not conduct them as per our written agreement

NCI’s “fact sheet” tries to obscure that simple fact with misinformation such as the following:

“In 1991, a “best case series” review was conducted by the National Cancer Institute (NCI) to evaluate clinical response in a group of patients treated at Dr. Burzynski’s Houston facility

For this review, Dr. Burzynski selected from his entire clinical experience 7 brain tumor patients whom he felt had a beneficial effect from antineoplastons.”

This misstatement is obviously calculated to make the reader think that in my entire clinical experience I have had only 7 patients who benefitted from antineoplaston treatment, which is wildly untrue

In fact, I prepared not 7, but dozens of cases for the NCI reviewers

As you must know, the reviewers were able to spend just one day at the clinic–enough time to review only 7 cases

Cancernet then compounds that misstatement with the following:

“This series did not constitute a formal clinical trial, since it was a retrospective review of medical records, did not include all available information, and included only cases selected by Dr. Burzynski” (my italics)

To the contrary, the patient medical records that NCI scientists reviewed were exhaustive and did contain “all available patient information.”

In fact, Michael Hawkins, M.D., leader of the site visit team, specifically complimented me on how complete and well-organized they were

The next misstatement is the following:

“The reviewers of this series determined that there was presumptive evidence of antitumor activity . . .”

Pg. 2

Now that the NCI’s Cancer Therapy Evaluation Program (CTEP) is under fire for misconduct in these clinical trials, it is rewriting history

The statement of the NCI scientists who actually reviewed patient records was quite different from the above

Their report (minutes of Decision Network committee meeting enclosed) stated that “The site visit team determined that antitumor activity was documented in the best case series and that the conduct of Phase II trials was indicated to determine the response rate” (my italics)

In other words, according to the site visit team, there was no question that the treatment worked in the cases reviewed

All that remained to be determined were the numerator and the denominator

Even the NCI’s own previous “fact sheet” on antineoplastons, dated 2/17/1994, (enclosed), states that

“The NCI reviewed 7 cases of patients with primary brain tumors that were treated by Dr. Burzynski with antineoplastons and concluded that antitumor responses occurred” (my italics)

But by far the most outrageous misstatement is the following:

“On 8/18/1995, the studies were closed because a consensus could not be reached with Dr. Burzynski on the proposed changes to the protocol to increase accrual, and there was no hope of completing the studies in a timely manner.”

The NCI never made any effort to “reach a consensus.”

Instead, it simply violated the written protocol we had agreed upon

Without informing me, NCI changed the rules to allow patients with any size or number of tumors, low performance scores, and spinal cord metastases

in other words, NCI was accepting patients whose brains and spinal cords were literally consumed by large malignant tumors–patients so advanced as to have no chance whatsoever

When I found out and insisted that NCI either conduct the study as agreed or inform patients that I felt it was conducting the study improperly, NCI cancelled it

The above is all well documented

While we were still in the negotiating stages, Michael Friedman, M.D. of the NCI wrote me a letter dated 11/2/1993 (enclosed) “. . . we will accede to all the modifications that you have stipulated.”

Dr. Friedman specifically agreed to exclude patients with:

* tumors larger than 5 cm (2 inches)
* multiple tumors
* metastases to spinal cord
* Karnofsky performance scores less than 70%

Based on Dr. Friedman’s written assurance that NCI would honor this exclusion criteria, I provided NCI with a large quantity of antineoplastons, and the clinical trial began

on 3/23/1994, Mario Sznol, M.D., of NCI wrote me proposing that NCI drop the exclusion for multiple tumors and spinal cord metastases, increase the maximum tumor size from 5 cm to 8 cm, and lower the Karnofsky score from 70 to 60 (enclosed)

in a response dated 4/19/1994 (enclosed), I wrote back that I would be glad to help NCI design a separate trial for such advanced patients, using a more aggressive dosage schedule

But I made it clear that it would be unethical to use the current dosage schedule on such patients since my experience had shown that such patients do not respond well to it

Pg. 3

As proof , I pointed out that in the NCI’s own review of patients treated with antineoplastons, the only ones who had less than 50% tumor shrinkage were exactly those with tumors greater than 5 cm

I did not hear back from NCI and assumed the matter had been dropped

Nearly one year later–in 3/1995–I learned that NCI had made all the changes to which I had objected

In fact, NCI went even further

Rather than raising the maximum tumor size from 5 to 8 cm as the NCI earlier suggested, it began accepting patients with any size tumor

I insisted that NCI either honor our agreement or change the Informed Consent statement (which patients must read and sign) to reflect the fact that I, the drug’s discoverer and developer, felt that the treatment was unlikely to be effective in such advanced patients in the doses being used

Rather than honor it’s commitment to conduct the study as agreed, NCI cancelled it

I find it particularly curious that now neither NCI nor Memorial Sloan-Kettering Cancer Center (MSK) will take responsibility for changing the exclusion criteria, and are instead pointing fingers at each other

in his letter of 4/3/1995 (enclosed), Dr. Sznol repeatedly refers to the “revised” eligibility criteria proposed by the [Memorial Sloan-Kettering] investigators” (my italics)

But, in a letter to John Lewis, M.D., of Memorial Sloan-Kettering’s Institutional Review Board dated 1/31/1995 (enclosed), the Chief Investigator, MSK’s Mark Malkin, M.D., writes that

“Further amendments, as described below, have been made at the request of NCI” (my italics)

If the changes to the protocol are as the NCI would have the world believe, why is everyone connected to them scurrying to disavow responsibility?

An even more serious matter is what appears to be the investigator’s relentless violations of the treatment protocol

Looking at the treatment summaries compiled by Theradex Corporation, the medical reporting company hired by NCI to compile and tabulate patient treatment data, it would appear that investigators violated the agreed-upon protocol in every patient treated

Apparent violations include the removal of patients from treatment who had no tumor growth (including one patient who, during subsequent surgery, was found to have no cancer cells remaining), and the removal of a patient for “skin reactions” caused not by antineoplastons, but by another drug patient was receiving, DPH

This is clear due to the fact that the patient’s skin condition worsened when he was taken off antineoplastons

It improved only after DPH was discontinued

The summaries provided by Theradex are somewhat sketchy, so I asked to review the complete records of patients tested–which Dr. Friedman had specifically promised to provide

NIH lawyer Robert Lanman replied in a letter dated 8/23/1995 (enclosed) that the NCI did not have any such records

In fact, several patients were treated at NCI and of course NCI has their complete medical records

When I demonstrated this by sending Mr. Lanman copies of patient records obtained by a patient’s family from NCI, he admitted in fact NCI does have patient records, but refused to release them

And he disregarded his own misstatements of fact by saying that

“Given that you apparently have already obtained at least one of the patient’s records, we fail to understand why you are perusing this matter” (letter from Robert Lanman dated 10/5/1995 enclosed)

Mr. Lanman also claims that NCI has “no such commitment” to release medical records of patients treated with antineoplastons

And Dr. Friedman, in a letter dated 9/19/1995 (enclosed), writes that Dr. Burzynski’s request for “detailed records” has been satisfied by the sketchy Theradex treatment summaries

Pg. 4

Both these statements directly contradict Dr. Friedman’s letter of 11/2/1993 (enclosed), in which he promises that

“In accordance with your letter, we will arrange a review of data after accrual of the 1st 5-6 patients, which should occur 6 months after the study has been initiated

This should be sufficient to assure that the conduct of the study is satisfactory

The Theradex database is also available . . .” (my italics)

In other words, Dr. Friedman promised to provide me with patient medical records, recognizing that the Theradex summaries are something quite separate

In that same 9/19/1995 letter, Dr. Friedman writes that

“We have no individual patient records in our possession in addition to the Theradex reports.”

Either he is deliberately misstating the facts, or he is out of touch with the Cancer Therapy Evaluation Program that he runs

Dr. Klausner, I request that you immediately withdraw the “fact sheet” the NCI is distributing which contains numerous and outrageous misstatements and distortion of fact

Thank you for your attention to this matter

SRB/cf

cc:

3+ pgs cc:
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1993 (11/2/1993) – Dr. Michael Friedman to Burzynski
1994 (2/17/1994) – NCI “fact sheet”
1994 (3/23/1994) – Dr. Mario Sznol to Burzynski
1994 (4/19/1994) – Burzynski to Dr. Mario Sznol
1995 (1/31/1995) – Dr. John L. Lewis
1995 (4/3/1995) – Dr. Mario Sznol to Burzynski
1995 (8/18/1995) –
1995 (8/23/1995) – Robert B. Lanman to Burzynski
1995 (9/19/1995) – Dr. Michael A. Friedman to Burzynski
1995 (10/5/1995) – Robert B. Lanman to Burzynski
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[18] – 1995 (5/16/1995) – Burzynski to Dr. Michael A. Friedman

This page is linked to:
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Critiquing: Dr. Michael A. Friedman, Dr. Mark G. Malkin, Dr. Mario Sznol, Robert B. Lanman, Memorial Sloan-Kettering Cancer Center, Mayo Clinic, Department of Health & Human Services (HHS), Public Health Service, Quality Assurance and Compliance Section, Regulatory Affairs Branch (RAB), Cancer Therapy Evaluation Program (CTEP), Division of Cancer Treatment (DCT), National Cancer Center (NCI) at the National Institutes of Health (NIH), Stanislaw Burzynski: On the arrogance of ignorance about cancer and targeted therapies
——————————————————————
https://stanislawrajmundburzynski.wordpress.com/2013/09/08/critiquing-stanislaw-burzynski-on-the-arrogance-of-ignorance-about-cancer-and-targeted-therapies/
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[18] – 1995 (5/16/1995) – Burzynski letter to Michael A. Friedman, M.D., Associate Director, Cancer Therapy Evaluation Program (CTEP), Division of Cancer Treatment (DCT), National Cancer Institute (NCI), National Institutes of Health (NIH)

Thank you for your letter of 5/12/1995

You are correct in asserting that I raise issues of ethical misconduct, failure to obtain adequate informed consent and scientific misjudgment

To be exact, my letter points out specific violations of the clinical trial protocol made by the current investigators

I provided careful documentation of some of the most egregious violations, including the removal of a patient from the study who had no increase in tumor size and the inclusion of a patient with tumor pathology that did not meet the entry criteria

It seems possible that, in at least one one of these cases, failure to follow the protocol resulted in the patient’s unnecessary death

In this case, the patient was removed from the study following an MRI dated 5/2/1994

The conclusion of neuroradiologist Jim Cain, MD, is that this MRI shows that the tumor had not grown, and no new tumors are present

As you know, the protocol calls for patients to be taken off treatment if the tumor grows 50% or more, or a new tumor is present

This is, as you point out, a most serious matter, and I was hoping that you could allay my concerns by showing me where they are unfounded

However, your letter conspicuously fails to address them

You also make reference to “numerous factual misstatements” but fail to identify any of them, much less provide documentation to show they are false

Pg. 2

Contrary to another of your statements, I did provide “specific clinical data which support” my contention that patients with large tumors do not respond well to the current protocol

Let me repeat from here

In the 1991 NCI review of 7 brain tumor cases, the only 2 patients with tumor size greater than 5.1 cm were also the only 2 patients to have less than 50% reduction of their tumor

The correlation between large tumor size and failure to respond is obvious

I am happy to learn that the trials have been put on hold

I must insist that they not be re-activated until I am satisfied that new investigators have been found who are capable of following the protocol — the original protocol on which we both agreed

As you know, the protocol was changed without anyone bothering to seek my advice, and certainly without my consent

I am glad that you plan to “thoroughly examine the accusations” I have made

However, this review must not be done by the people responsible for the violations being investigated

This would amount to a whitewash of the whole affair, and is unacceptable

The review must be done by an independent body of experts acceptable to both of us

Otherwise it will be meaningless

I still have not received the complete data on the 1st 5 patients, which was promised in your letter of 4/3/1995

I hope to receive the data soon

I also eagerly await a substantiative response to the points raised in my letter of 4/20/1995

cc:

Senator Joseph Biden
Senator Barbara Boxer
Senator Diane Feinstein
Senator Tom Harkin
Senator Barbara Mikulski
Congressman Berkley Bedell
Congresswoman Nancy Pelosi
Dr. Jan Buckner
Dr. Jay Greenblatt
Mr. Richard Jaffe
Dr. Wayne Jonas
Mr. Robert Lanman
Ms. Mary McCabe
Dr. Mark Malkin
Dr. Tony Murgo
Dr. Ralph Moss
Dr. David Parkinson
Dr. Edward Sondik
Dr. Mario Sznol
Dr. Dorothy Tisevich
Dr. Alan Trachtenberg
Mr. Frank Wiewel
Dr. Robert Wittes
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1995 (5/16/1995) – Burzynski to [15]
(2 pgs.)
1991 NCI review of 7 brain tumor cases
1994 – 5/2/1994 – MRI
1995 (4/3/1995) – Dr. Michael A. Friedman to Burzynski
1995 (4/20/1995) – Burzynski to
1995 (5/12/1995) – Dr. Michael A. Friedman to Burzynski
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[14] – 1995 (3/29/1995) – Burzynski to Dr. Michael A. Friedman (2 pgs.)

This page is linked to:
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Critiquing: Dr. Michael A. Friedman, Dr. Mark G. Malkin, Dr. Mario Sznol, Robert B. Lanman, Memorial Sloan-Kettering Cancer Center, Mayo Clinic, Department of Health & Human Services (HHS), Public Health Service, Quality Assurance and Compliance Section, Regulatory Affairs Branch (RAB), Cancer Therapy Evaluation Program (CTEP), Division of Cancer Treatment (DCT), National Cancer Center (NCI) at the National Institutes of Health (NIH), Stanislaw Burzynski: On the arrogance of ignorance about cancer and targeted therapies
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https://stanislawrajmundburzynski.wordpress.com/2013/09/08/critiquing-stanislaw-burzynski-on-the-arrogance-of-ignorance-about-cancer-and-targeted-therapies/
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[14] – 1995 (3/29/1995) – Burzynski to Dr. Michael A. Friedman (2 pgs.)
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Michael A. Friedman, M.D., Associate Director,Cancer Therapy Evaluation Program, Division of Cancer Treatment, NCI, National Institutes of Health

Dear Dr. Friedman,

It has been brought to my attention that the protocol

“Phase II Study of Antineoplastons A10 and AS2-1 in Patients with Advanced Recurrent Malignant Astrocytomas”

has been amended to accept patients with tumors measuring over 5 cm in diameter, multiple tumors, or with leptomeningeal or systemic metastases

Another change involves lowering of the Karnofsky Performance Status score to 60%

You assured me in your letter of 11/2/1993 that

“The dose and schedule will be modified exactly as you require”

and

“The eligibility criteria will be modified to accept only patients with Karnofsky Performance Status of 70% – 100%

I am outraged that without my knowledge Memorial Sloan-Kettering Cancer Center with NCI’s permission changed the protocol

Treatment of patients with tumors larger than 5 cm, with multiple tumors, and leptomeningeal spread or distant metastases will require a different protocol with a different schedule and different dosages

the use of the existing protocol for such very advanced brain tumor patients will only expose them to unnecessary risks without giving them substantial benefit

I hereby request that the amendments described above be cancelled immediately and the original protocol be used for the treatment as promised in your letter of 11/2/1993

We will be glad to propose a different protocol for patients with larger and multiple tumors and meningeal involvement

In addition, the procedure we agreed upon calls for a thorough review by us of the 1st 5 patients as soon as they are accrued

Your last annual report indicates

Pg. 2

that you had accrued that number of patients 6 months ago

As a result, the review of data is long overdue

Please send us the complete records of the 1st 5 patients so that we may review them as specified

Please do not accrue any more patients until this data has been sent and our review completed

SRB/cf

cc:

Dr. Jan Bruckner
Dr. Michael C. Christian
Dr. Jay Greenblatt
Dr. Mark Malkin
Ms. Mary McCabe
Dr. David Parkinson
Dr. Mario Sznol
Ms. Dorothy Tisevich
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1993 (11/2/1993) – Dr. Michael A. Friedman to Burzynski
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[13] – 1995 (1/31/1995) – Dr. Mark G. Malkin to Dr. John L. Lewis (1 pg.)

This page is linked to:
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Critiquing: Dr. Michael A. Friedman, Dr. Mark G. Malkin, Dr. Mario Sznol, Robert B. Lanman, Memorial Sloan-Kettering Cancer Center, Mayo Clinic, Department of Health & Human Services (HHS), Public Health Service, Quality Assurance and Compliance Section, Regulatory Affairs Branch (RAB), Cancer Therapy Evaluation Program (CTEP), Division of Cancer Treatment (DCT), National Cancer Center (NCI) at the National Institutes of Health (NIH), Stanislaw Burzynski: On the arrogance of ignorance about cancer and targeted therapies
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https://stanislawrajmundburzynski.wordpress.com/2013/09/08/critiquing-stanislaw-burzynski-on-the-arrogance-of-ignorance-about-cancer-and-targeted-therapies/
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[13] – 1995 (1/31/1995) – Dr. Mark G. Malkin to Dr. John L. Lewis (1 pg.)
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T93-0078

John L. Lewis, M.D., Chairman, Institutional Review Board, Memorial-Sloan-Kettering Cancer Center

RE: Protocol # 93-105

Dear Dr. Lewis

You will find appended to this covering letter an amended version of the approved IRB protocol # 93-105, entitled

“Phase II Study of Antineoplastons A10 and AS2-1 in Patients with Advanced Recurrent Malignant Gliomas”

Further amendments, as described below, have been made at the request of NCI

The minor textual changes expand the pool of eligible patients, thus permitting us to recruit patients more rapidly; however, they do not otherwise alter the overall design of the protocol

1. In Sections 1.1-b) and 6.1-i) the permissible Karnofsky Performance Status Score has been lowered from 70% to 60%

2. In Sections 1.1-k) and 6-2.a) the exclusion criteria have been changed

The statement:

“Patients with tumors > 5 cm in diameter, multifocal turmors, or with laptomeningeal or systematic metastases are excluded

has been replaced by the statement:

There will be no exclusion based on tumor size, multifocality, or leptomeningeal or systemic metastases

I thank you for your assistance in this matter

Mark Malkin, M.D.

cc:

Jerome Posner, M.D.
Charles Young, M.D.
Mario Sznol, M.D. (NCI)
NCI-designated Comprehensive Cancer Center
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1995 (1/31/1995) – to Dr. John L. Lewis [20]
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[9] – 1993 (11/2/1993) – Dr. Michael A. Friedman to Burzynski

This page is linked to:
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Critiquing: Dr. Michael A. Friedman, Dr. Mark G. Malkin, Dr. Mario Sznol, Robert B. Lanman, Memorial Sloan-Kettering Cancer Center, Mayo Clinic, Department of Health & Human Services (HHS), Public Health Service, Quality Assurance and Compliance Section, Regulatory Affairs Branch (RAB), Cancer Therapy Evaluation Program (CTEP), Division of Cancer Treatment (DCT), National Cancer Center (NCI) at the National Institutes of Health (NIH), Stanislaw Burzynski: On the arrogance of ignorance about cancer and targeted therapies
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https://stanislawrajmundburzynski.wordpress.com/2013/09/08/critiquing-stanislaw-burzynski-on-the-arrogance-of-ignorance-about-cancer-and-targeted-therapies/
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[9] – 1993 (11/2/1993) – Michael A. Friedman, M.D., Associate Director, Cancer Therapy Evaluation Program (CTEP), Division of Cancer Treatment, National Cancer Institute (NCI), Department of Health & Human Services (HHS), Public Health Services, National Institutes of Health (NIH) to Burzynski [3 pgs.]

Department of Health and Human Services, Public Health Services, National Institutes of Health

Dear Dr. Burzynski:

With regard to your letter of 10/26/1993, you specifically state

“The medicine will be sent to you immediately once you make the corrections to the protocol that we have requested”

We have substantial factual disagreements and scientific reservations with many of the comments made in your 10/26/1993 letter, including your preposterous claim that the NCI wasted 8 months

Nonetheless, we will accede to all the modifications that you have stipulated

We do so because we are committed to beginning the clinical studies as quickly as possible

We presume that these are your final comments, since all the changes will have been made and we will have addressed all of your concerns regarding these studies

The revised protocol will be sent to you as soon as it is received from the investigators

Based on the promise in your letter, we expect that the drug will be shipped to the NCI repository the next day

The changes to made to the protocol are as follows:

1. The dose and schedule will be modified as exactly as your require

We believe this to be the dose and schedule found in your protocol BT6, with dose escalation and maximum dose guidelines for adults clarified in your letter of 10/13/1993

2. The Memorial study, as written, has 2 separate components, one for patients with glioblastoma multiforme and one for patients with anaplastic astrocytoma

Accrual to each stratum proceeds independently, and analyses of each stratum is separate

However, we will ask the investigators from Mayo Clinic to join the Memorial study, rather than conducting an independent trial

This will effectively evaluate on the one hand patients with glioblastoma multiforme, and on the other hands those with anaplastic astrocytoma

Pg. 2

Patients with either disease will be enrolled at both Memorial and Mayo sites

This modification has 2 advantages — it limits total accrual to 35 patients per histology, as you request; and it accelerates accrual, since each institution can enter both types of patients on the studies

3. As you stipulated, Fleming’s original statistical design will be used utilized
15 patients will be entered independently to each stratum; for each stratum, if there is 1 response, accrual will proceed to a total of 35 patients

Thus total accrual will be 70 patients if both strata proceed past the 1st stage

(the initial 15 patients per histology)

4. According to your wishes, all scans for tumor measurements and laboratory test will be performed within 7 days of initiating protocol therapy, rather than the standard 14 days now specified in the protocol

5. The eligibility criteria will be modified to accept only patients with a Karnofsky performance status of 70-100%

6. As you require, the protocol response criteria will be based on objective tumor measurements and will not include assessment of neurologic status

Neurologic status will be evaluated separately

7. In accordance with your letter, we will arrange a review of data after accrual of the 1st 5-6 patients, which should occur 6 months after the study has been initiated

This should be sufficient to assure that the conduct of the study is satisfactory

The Theradex database is also available to precisely determine if the conduct of the study has followed protocol guidelines; the study centers will also be audited on-site by Theradex (independent contractors) every 3 months

In your letter you express concern regarding what you perceive to be bias against alternative treatments by Mayo Clinic and Memorial investigators

Please note that the investigators participating in the antineoplaston studies volunteered to do so because of the findings of the NCI review of your best case series

To my knowledge none of the participating investigators have expressed (publicly or privately) a position for or against Antineoplastons

Both institutions have a distinguished record in clinical investigations, and have been leaders in subjecting all treatments (including alternative interventions) to fair and objective clinical research

We are confident that credible clinical studies will be conducted

Pg. 3

Finally, if even after modifying these studies in accordance with your stated wishes, you are unwilling to supply the antineoplaston materials, please inform me as quickly as possible

We will then seek alternative sources of this family of molecules for proper clinical evaluation

Michael A. Friedman, M.D., Associate Director, Cancer Therapy Evaluation Program, Division of Cancer Treatment, NCI

cc:

Dr. Samuel Broder
Dr. Jan Bruckner
Dr. Bruce Chabner
Dr. Jay Greenblatt
Dr. Joseph Jacobs
Dr. Mark Malkin
Ms. Mary McCabe
Dr. David Parkinson
Dr. Mario Sznol
Ms. Dorothy Tisevich
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1993 (11/2/1993) – Dr. Michael A. Friedman to SRB [9]
1993 (11/2/1993) – Dr. Michael A. Friedman to Burzynski [14]
1993 (11/2/1993) – Dr. Michael A. Friedman to SRB [19] (3 pgs.)
1993 (11/2/1993) – Dr. Michael A. Friedman to Burzynski [24]
1993 (10/13/1993) – Burzynski to Dr. Michael A. Friedman
1993 (10/26/1993) – Burzynski to Dr. Michael A. Friedman
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[8] – 1993 (10/26/1993) – Burzynski to Dr. Michael A. Friedman

This page is linked to:
=====================================
Critiquing: Dr. Michael A. Friedman, Dr. Mark G. Malkin, Dr. Mario Sznol, Robert B. Lanman, Memorial Sloan-Kettering Cancer Center, Mayo Clinic, Department of Health & Human Services (HHS), Public Health Service, Quality Assurance and Compliance Section, Regulatory Affairs Branch (RAB), Cancer Therapy Evaluation Program (CTEP), Division of Cancer Treatment (DCT), National Cancer Center (NCI) at the National Institutes of Health (NIH), Stanislaw Burzynski: On the arrogance of ignorance about cancer and targeted therapies
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https://stanislawrajmundburzynski.wordpress.com/2013/09/08/critiquing-stanislaw-burzynski-on-the-arrogance-of-ignorance-about-cancer-and-targeted-therapies/
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[8] – 1993 (10/26/1993) – Burzynski to Dr. Michael A. Friedman
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Dear Dr. Friedman,

In response to your letter of 10/20/1993, it is difficult for me to understand why the entire 1st page of your letter is used to discuss the simplest issue:

that adults should use a different dosage than that used for children

Since you agreed to the study procedure of Protocol BT-6 as recommended in my letter of 6/9/1993, we have not requested any changes in the structure of treatment which was accepted by Memorial-Sloan-Kettering Cancer Center (MSKCC)

As you confirmed in your letter of 10/20/1993, you know very well that since 4/1/1993 of this year my recommended dosage of Antineoplaston AS2-1 for adults is 0.4g/kg/24h

Again, I confirmed that this is the right dosage for adults in my letter to Dr. Shoemaker of 8/24/1993

Yet, for no apparent reason, you insist on using in the adult treatment protocol the dosage 0.6g/kg/24h which I recommend for children

It is generally known that a child’s body weight is much lower than that of adults

This should be reflected in the escalation of the dosages

My recommendation as to how to escalate the dosages for adults was submitted to the NCI on 6/4/1992

Yet, for no apparent reason the MSKCC protocol, which is designed for adults, escalates the dosages in the small increments recommended for children

The principle behind dose escalation is to accomplish the maximum dosage in 3 to 5 days, not 3 to 4 weeks, which would expose the patient to the unnecessary risk of tumor progression

I appreciate very much that you have finally decided to follow my recommendation regarding dosage and dosage escalation

Regarding the number of patients to be treated at MSKCC, the contradictory, incomplete, and inconsistent information is being supplied by you

The MSKCC’s protocol of 4/16/1993, 7/13/1993, and 8/30/1993 describe the treatment of 35,

Pg. 2

but not 70 patients

(please see paragraph 12.1, pg. 10 of the protocol, which is attached)

It was our understanding that 35 patients would be treated at MSKCC and at the Mayo Clinic

I never agreed for the treatment of 70 patients at MSKCC

Since I have to produce the medicine for the trial and pay for it, it is vitally important to me to know how many patients will be treated

The treatment of an additional 35 patients may cost up to 2 million dollars

Contrary to the information given by NCI that we received the money for the production of medicine, this money went apparently into a “black hole”

(“Black Holism,” The Village Voice, 7/29/1993, enclosed)

We have received none of the money which the Office of Alternative Medicine gave to the NCI for funding the trials with our medicine

Contrary to the opinion expressed in your letter, we see no reason for modifying Fleming’s Phase II clinical trial design and introducing more stringent than usual criteria for response evaluation

We request that Fleming’s original design be used, which calls for the initial treatment of 15 patients with at least one responder, instead of 20 patients and 2 responders

Given the fact that there is no existing treatment effective in this type of cancer, one responder in 15 is certainly significant and would be reason enough to expand the trial

I found your your requirement for 14 days to complete scans and laboratory tests prior to treatment very interesting

It is a very well known fact that glioblastoma multiforme is such an active tumor that if 2 weeks elapses from the time of the scan and the beginning of treatment, the tumor may increase by more than 50%

This means that even before the patient begins treatment, he can be classified as an increasing disease case

In most of the hospitals in the U.S., including out tiny clinic, all pretreatment tests including the scans can be done in one day

Therefore, I insist that the pretreatment evaluation, including brain scans, be done within 7 days from the time treatment begins

Regarding the Karnofsky Performance Status (PS), it is unclear to me why you have backed off from your own recommendation in your letter of 5/5/1993 (copy attached) that “patients with Karnofsky PS of below 70% should be excluded”

I am requesting that as recommended by NCI, the patient’s PS should be 70% to 100%

I agree that both scan data and neurological assessment can be described in the analysis of response, but the decision of how to classify response should be based on tumor measurements alone

All of these patients will have been extensively treated before

As the result of previous neurotoxic treatments, a number of these patients will deteriorate neurologically even if the Antineoplastons eradicate the

Pg. 3

tumor

The purpose of the protocol is to evaluate the antitumor effect, not to prove that Antineoplastons can repair brain damage resulting from chemotherapy and radiation

In this 1st independent study with Antineoplastons, in order to assure that patients will derive the most benefit from the treatment, it is critically important to schedule more frequent evaluations of the data than waiting until after the accrual of 14 patients, i.e. waiting 9 months

(Based on an accrual of 2 patients per month, if we wait until 14 patients are accrued and treated, 9 months will pass before the 1st evaluation takes place)

Therefore, I request that reviews of the studies be performed after the treatment of each group of 5 patients, i.e. after 6 months

I agree, however, that you will provide the Theradex printout to us as you receive it

In addition to patient welfare, there is another reason for more frequent patient evaluations

As you stated in your letter, I have no doubt that the investigators at MSKCC have extensive experience treating glioma

However, MSKCC is known to be biased against Antineoplastons

At least 3 researchers associated with MSKCC published willful misrepresentations and distortions about Antineoplaston research

Because of the controversial nature of the upcoming Antineoplaston clinical trials, it is essential that they are conducted in a manner beyond any suspicion of bias

Contrary to the opinion expressed in your letter, NCI is responsible for the trial’s delay

As you well know, the NCI selected an MSKCC investigator in 9/1992

In spite of our repeated requests, 8 months were waisted before the NCI produced the 1st draft of the protocol

As promised in my letter to you of 11/11/1992, the supply of Antineoplastons has been prepared and was shown to Ms. Mary McCabe of NCI during the site visit on 2/9/1993

The medicine was ready to be released pending final approval approval of the labels by the FDA and our final QC inspection

The medicine will be sent to you immediately once you make the corrections to the protocol that we have requested

Since you mentioned that patient recruitment has begun already, I would be glad to accept these patients immediately under my care and offer them free medicine as we wait for the protocol to be revised and the treatment at MSKCC to begin

The MSKCC protocol in its current form would threaten the welfare of these patients

In your letter you stated that your mission is to find and develop better therapies for cancer patients, and that your only obligation is to those patients

However, the way

Pg. 4

you proceed leads me to question that for the following reasons:

1) Out of numerous cancer treatment centers, you selected 2:

MSKCC and Mayo Clinic, which are known to be strongly biased against alternative treatments

In the past doctors associated with MSKCC have voiced strong opposition to Antineoplaston therapy and have published articles full of misrepresentations and distortions

2) The protocol approved by you will allow the disease to progress between the pretreatment evaluation and the beginning of treatment

3) Due to the slow escalation of dosages, patients will most likely have marked increase of tumor size beginning the treatment at the correct dosage level

4) In spite of my numerous requests (letters of 4/29/1993, 6/9/1993, and 8/24/1993) to proceed following the guidelines of the NCI’s Decision Network on 12/2/1991 to have a separate clinical trial for glioblastoma multiforme and anaplastic astrocytoma, you continue to combine both types of tumors together

Even in your most recent stratification strategy submitted to the FDA, you are planning to treat initially 20 patients without specifying whether those 20 patients are per each stratum (glioblastoma vs. anaplastic astrocytoma), or whether this initial group of 20 patients consist of a mixture of glioblastoma and anaplastic astrocytoma

If the latter is the case, then we can expect that among these 1st 20 patients, most will have glioblastoma, which is more common and more difficult to treat

In case of treatment failure in these 20 patients, it will be easy to make the statement that Antineoplastons do not have therapeutic effect in both tumor categories

5) The protocol now states in paragraph 10.2, 10.3, and 10.4 that the objective decrease of tumor size is not enough to be considered a true response to treatment, that there must also be improvement in neurological function

As I explained in my letter of 10/13/1993 to Dr. Greenblatt, it is not unusual in my practice to see patients whose tumor has disappeared, but who have deteriorated neurologically as the result of delayed toxicity from radiation therapy and chemotherapy

Since these patients in the MSKCC study have been pretreated, and since there has been no indication that anything, including Antineoplastons, can repair brain damage caused by chemotherapy and radiation, I request that the criteria including restored neurological functioning be removed from paragraphs 10.2, 10.3, and 10.4 of the protocol

Pg, 5

6) Finally, by limiting our access to the data and not allowing review until after the 1st 14 patients have been treated, it would be easy to deviate from the protocol and supply inadequate treatment, and then claim that due to the the failure of the 1st 14 patients it would be a waste of the taxpayers money to proceed with further treatment

Your final statements that you are ready to proceed with the treatment with Antineoplastons without our participation caught me by surprise

It is hard to imagine that a Federal employee would consider patent infringement, thus infringing on the patent rights of thousands of our shareholders

Once again, I urge you to take our requests seriously, honor the guidelines of the NCI’s Decision Network on 12/2/1991, and make proper corrections to the protocol, so that objective clinical studies can begin immediately

In the meantime, I would be glad to treat for free all the patients presently recruited, and will submit progress reports weekly for the NCI’s review and evaluation

SRB/cf

cc:

Senator Joseph Biden
Senator Barbara Boxer
Senator Dianne Feinstein
Senator Tom Harkin
Senator Barbara Mikulski
Congressman Berkley Bedell
Congresswoman Nancy Pelosi
Dr. Samuel Broder
Dr. Jan Buckner
Dr. Bruce Chabner
Dr. Daniel Eskinazi
Dr. Jay Greenblatt
Dr. Joseph Jacobs
Dr. Mark Malkin
Ms. Mary McCabe
Dr. David Parkinson
Dr. Mario Sznol
Ms. Dorothy Tisevich
======================================

======================================
1993 (10/26/1993) – SRB to [5]
1993 (10/26/1993) – SRB to [14]
1991 (12/2/1991) – guidelines of the NCI’s Decision Network [5 Pgs.]
1992 (6/4/1992) Burzynski to NCI
1992 (9/1992) – NCI selected MSKCC investigator
1992 (11/11/1992) – Burzynski to Dr. Michael A. Friedman
1993 (2/9/1993) – NCI Mary McCabe site visit
1993 (4/1/1993) –
1993 (4/16/1993) – MSKCC protocol
1993 (4/29/1993) – Burzynski to
to proceed following the guidelines of the NCI’s Decision Network on 12/2/1991
1993 (5/5/1993) – Dr. Michael A. Friedman to Burzynski
1993 (6/9/1993) – Burzynski to
to proceed following the guidelines of the NCI’s Decision Network on 12/2/1991
1993 (7/13/1993) – MSKCC protocol
1993 (7/29/1993) – “Black Holism,” The Village Voice
1993 (8/24/1993) – Burzynski to Dr. Dale Shoemaker
to proceed following the guidelines of the NCI’s Decision Network on 12/2/1991
1993 (8/30/1993) – MSKCC protocol
1993 (10/20/1993) – Dr. Michael A. Friedman to Burzynski
======================================

[7] – 1993 (10/20/1993) – Dr. Michael A. Friedman to Burzynski (4 pgs.)

This page is linked to:
=====================================
Critiquing: Dr. Michael A. Friedman, Dr. Mark G. Malkin, Dr. Mario Sznol, Robert B. Lanman, Memorial Sloan-Kettering Cancer Center, Mayo Clinic, Department of Health & Human Services (HHS), Public Health Service, Quality Assurance and Compliance Section, Regulatory Affairs Branch (RAB), Cancer Therapy Evaluation Program (CTEP), Division of Cancer Treatment (DCT), National Cancer Center (NCI) at the National Institutes of Health (NIH), Stanislaw Burzynski: On the arrogance of ignorance about cancer and targeted therapies
——————————————————————
https://stanislawrajmundburzynski.wordpress.com/2013/09/08/critiquing-stanislaw-burzynski-on-the-arrogance-of-ignorance-about-cancer-and-targeted-therapies/
======================================
[7] – 1993 (10/20/1993) – Dr. Michael A. Friedman to Burzynski (4 pgs.)

Michael A. Friedman, M.D., Associate Director, Cancer Therapy Evaluation Program (CTEP), Division of Cancer Treatment, National Cancer Institute (NCI), Department of Health & Human Services (HHS), National Institutes of Health (NIH) letter to Burzynski [4 Pgs.]

Dear Dr. Burzynski:

This letter is in response to your correspondence of 10/11/1993

(addressed to Dr. Sznol)

and of 10/13/1993

(to Dr. Greenblatt)

Your most recent comments regarding the approved study of antineoplastons in adults brain tumor patients, faxed to Dr. Greenblatt on 10/13/1993, come as quite a surprise

Particularly confusing are your comments regarding dose and schedule of antineoplastons proposed in that study (your comment #1)

Originally the dosage and schedule for this study was based on your protocol BT4

This version of BT4 was entitled,
“Therapy of high-grade glioma with continuous infusions of antineoplastons A10 and AS2-1”,
and was accompanied by 12 case histories

(patients with either anaplastic astrocytoma or glioblastoma multiforme treated apparently according to BT4)

In your letter of 4/26/1993, however you stated that protocol BT4 was only for low-grade gliomas

Furthermore, you noted that protocols BT5 or BT6 should be used for patients with anaplastic astrocytoma and gliobastoma multiforme

In that same letter (4/20/1993), you noted that AS 2-1 was tolerated well at doses of .5 gm/kg/24h by adult patients when administered in intermittent injections (this is method of administration in BT6 and in the IND study)

You stated that if given by continuous infusion, adults would experience increased sleepiness and tiredness, and specifically stated that the dosage of AS2-1 by continuous infusion for low-grade gliomas should be reduced to 0.4 g/kg/24h

You did not provide data to support these assertions, nevertheless, based on these comments and our review of the protocols BT4, BT5, BT6, we instructed the investigators to revise their protocol in accordance with your instructions

In the Consensus Review sent 5/5/1993, we instructed the Memorial Sloan Kettering investigators to pattern their protocol according to BT5, which was written for both children and adults
We specifically pointed out that BT6 was written for children

In your letter of 6/9/1993, regarding our Consensus Review, you specifically asked that the investigators use the treatment program according to BT6, knowing that the Memorial protocol was for adults with AA and/or GM

You did not at any time mention that dose escalation should be modified for adults, or mention any dose limitation for adults given the intermittent as specified in the BT6 protocol

Page 2

Your concerns regarding dose limitation in the previous letter appeared to be related to continuous infusion administration

The letter of 6/9/1993, contained only 4 comments and at that time you had both the protocol and Consensus Review in your possession

We transmitted your letter of 6/9 directly to the investigators, and all your requested changes were made

Our sincere efforts to attempt to duplicate your findings and follow your recommendations are frustrated by receiving contradictory, incomplete, and inconsistent information from you

We have, at multiple points in the protocol development, solicited your input and followed your guidance in getting recommended dose escalation and modification guidelines for adults

Please note that, one last time, we will ask the investigator to revise the protocol with regard to dose and schedule in compliance with your latest letter

However, we plan that the study will begin immediately and this will be the last such modification

Although you have not provided data to support each of your specific recommendation, we have incorporated them

With regard to comment #2 of your Fax of 10/13/1993, you have misinterpreted the protocol

The total number of potential patients is 35/stratum, (ie a total of 70 patients) allowing for an adequate Phase II evaluation of each group of patients

With regard to the statistical section, your #3 comment, there is little reason to assume that the modified Fleming design currently used in the protocol for the first stage of accrual is less appropriate than a design using 15 patients in the first stage

If the true response rate of the antineoplastons is 20% (standard criteria for activity in all our phase II trials considered worthy of further study), the chance of proceeding to the second stage of accrual with the current design is 93.1%

The chance of proceeding to the second stage using 15 patients in the first stage of accrual is 96.5%

These differences are not considered meaningful

With regard to your comment #4, we wish to maintain the standard clinical trials methodology used to evaluate new agents

We know of no evidence that obtaining a brain scan within 7 days of treatment versus within 14 days of treatment will in any way affect the evaluation of activity of a drug in this disease

The protocol clearly states that scans must be obtained within 2 weeks of study entry

Please also note that the practical difficulties in scheduling scans and completing the pretreatment work-up in just one week; the costs of repeating tests simply to meet this artificial deadline could not be justified and probably would not be covered by insurance companies

With regard to your point #5, (performance status) your own protocols allow patients with Karnofsky performance status of 60

We see no reason to demand a more stringent entry criteria for performance status than you have employed for your own patients

Page 3

With regard to your point #6, the use of neurologic status as well as CT scans/MRI findings to determine response, this was suggested to the investigators in our Consensus Review of 5/5/1993

You made no comment regarding this in your letter of 6/9/1993

This use of neurologic function as an additional criteria to determine response is an objective measurement and is standard among protocols we sponsor for glioma patients . .

It is scientifically acceptable to include the criteria for response as currently written in the protocol

At analysis, both scan data and objective neurologic assessment can be described

With regard to your letter of 10/11/1993, concerning data reviews, we are satisfied that reviewing the data after accrual of the first 14 patients/stratum is sufficient

We share your concerns about patient safety but believe that these investigators have extensive experience treating glioma patients, are superb and careful physicians, and have extensive experience administrating a range of investigational agents to these patients

Furthermore, the patients will be followed carefully, and dose reductions for expected toxicities will be carried out as specified in the protocol

Nevertheless, your experience with the agents is valuable and the availability of your guidance is much appreciated

If necessary, we will arrange a conference call at the end of treatment of the first 5 patients, or sooner if problems occur

Your participation in such a conference call, if necessary, would be welcome

We will provide the Theradex (CTMS) printout to you on a monthly basis as we receive it

We do not believe it is practical or necessary to supply data on an every 2 week basis

The most important unresolved issue at this time is that we are still waiting to receive the promised supply of antineoplastons to conduct these studies

Your letter of 11/5/1992, guaranteed a supply of the antineoplastons by 3/31/1993

(see attached)

As of today we still have not received it

Believing that you would be shipping drug to the NCI, and since the protocol is approved at Memorial Sloan Kettering, recruitment of patients has begun

As you point out, these patients have aggressive disease, and cannot afford to wait to begin treatment

We are prepared to try to assist you in meeting this commitment, but we know of no obstacle here at NCI

We urgently request, again, that you ship the drug immediately

Please be aware that our mission is to find and develop better therapies for cancer patients, and our only obligation is to those patients

Our agreement to pursue these studies with antineoplastons was based on suggestive evidence

Page 4

of activity noted in your best case studies

If you are unable or unwilling to provide the antineoplastons in the near future, we will pursue alternative sources to procure the drug or its active components, and will proceed with a clinical development plan to determine whether these chemicals have activity and are beneficial for patients

Michael A. Friedman, M.D., Associate Director, Cancer Therapy Evaluation Program, Division of Cancer Treatment, NCI, Department of Health and Human Services, National Institutes of Health

cc:

Dr. Samuel Broder
Dr. Jan Buckner
Dr. Bruce Chabner
Dr. Jay Grabnett
Dr. Joseph Jacobs
Dr. Mark Malkin
Ms. Mary McCabe
Dr. David Parkinson
Dr. Mario Sznol
Ms. Dorothy Tisevich
——————————————————————

======================================
1993 (10/20/1993) – Dr. Michael A. Friedman to Burzynski [8]
1992 (11/5/1992) – Burzynski ANP 3/31/1993
1993 (4/20/1993) – Burzynski (4/26/1993)? in that same letter
1993 (4/26/1993) – Burzynski
1993 (5/5/1993) – Consensus Review
1993 (6/9/1993) – Burzynski re Consensus Review
1993 (10/11/1993) – Burzynski to Dr. Mario Sznol
1993 (10/13/1993) – Burzynski fax to Dr. Jay Greenblatt
======================================

Critiquing: Dr. Michael A. Friedman, Dr. Mark G. Malkin, Dr. Mario Sznol, Robert B. Lanman, Memorial Sloan-Kettering Cancer Center, Mayo Clinic, Department of Health & Human Services (HHS), Public Health Service, Quality Assurance and Compliance Section, Regulatory Affairs Branch (RAB), Cancer Therapy Evaluation Program (CTEP), Division of Cancer Treatment (DCT), National Cancer Center (NCI) at the National Institutes of Health (NIH), Stanislaw Burzynski: On the arrogance of ignorance about cancer and targeted therapies

One of Dr. David H. “Orac” Gorski’s “Oracolytes,” a wooshipper of their Lord and Master, Lord Frackonis AstroidZeneca posted this “gem” of a comment on National Geographic’s (#NatGeo) scienceblogs . com/Insolence
——————————————————————
[A] – 4/30/2013 – #98 – Krebiozen – May.28, 2013

BTW, DJT appears to have completely unraveled on his blog, calling Orac, “a self-proclaimed “cancer researcher” ” making many other blatantly libelous statements, ranting on, and on, and on. He is clearly unwell. If anyone who knows him personally happens to read this, please get him some professional help.
——————————————————————
What does Krebiozen think Dr. David H. “Orac” Gorski is going to do since I’ve been giving the “big reveal” to some of his lies, misdirection, misinformation, and disinformation ?

Sue me for telling the truth about his lies ?
——————————————————————
[B] – 12/.5/2012 – Gorski posted:

“Indeed, one could argue that that’s why the FDA and the NCI couldn’t work with him” (Burzynski)

“They didn’t know him when they agreed to work with him in the 1990s, but as they worked with him over the course of a few years they learned his true nature, leading to an inevitable schism, which taught the NCI a lesson about the consequences of dealing with pseudoscientists”
——————————————————————
Does Gorski provide a “citation” for his claim ?

no !

Does he provide a “reference” ?

No !!

A “link” ?

NO !!!

So where did Gorski come up with this unsubstantiated claim ?

Well, it seems that Gorski has cited The Cancer Letter before without attribution
——————————————————————
[C] – 9/25/1998 – “Stanislaw Burzynski, a Polish-trained physician who initially produced antineoplastons by extracting them from human urine”
——————————————————————
[D] – 2/19/2013 – Now where have I seen a questionable statement like this before ?
——————————————————————
[E] – 1/14/2013 – Gorski posted: “As you might recall, antineoplastons are chemicals that Burzynski found in the urine of cancer patients … “
——————————————————————
[C] – 9/25/1998 – The Cancer Letter indicated that a:

“trial of antineoplastons, coordinated by NCI, began at Memorial Sloan-Kettering Cancer Center, the Mayo Clinic, and the NIH Clinical Center“
——————————————————————
And that the
——————————————————————
“trial, which tested Burzynski’s drug in advanced recurrent malignant glioma, accrued 9 patients and was aborted as a result of a dispute“

“The dispute generated a stack of mutually recriminating memos, in which Burzynski accused the investigators of attempting to scuttle the trial, while NCI officials responded with requests that Burzynski provide the data that would back his accusations
——————————————————————
[F] – 6/23/2013 – Gorski has already proved that he does NOT have what it takes to provide the answers for the National Cancer Institute (NCI) at the National Institutes of Health (NIH)
——————————————————————
[G] – 3/30/2013

Odd how @BurzynskiMovie pretends I haven't deconstructed his "evidence" in depth before. http://t.co/uiGeNelAlb @bbcpanorama @vguyuk @fxnwo

— David Gorski (@gorskon) March 30, 2013

NO, Dr. Gorski, you have NOT “deconstructed his” evidence “in depth before”

Burzynski: Cancer Is Serious Business (Part I) consists of the documentary; which covered some of this, as well as the documents on the movie web-site, which you have NOT “deconstructed … in depth before”, since you
“cherry-picked” what you reviewed

Allow me
=======================================
[1] – 10/4/1991 – Five doctors (3 from the Cancer Therapy Evaluation Branch (CTEP); including the Head of the Quality Assurance and Compliance Section, Regulatory Affairs Branch (RAB), Cancer Therapy Evaluation Program (CTEP), Department of Health & Human Services (HHS), Public Health Service, National Institutes of Health (NIH), National Cancer Institute (NCI), and 2 invited consultants; including one from the National Institutes of Health (NIH) Clinical Center) visited the offices of Dr. Stanislaw R. Burzynski
=======================================
[2] – 10/30/1991 – Dorothy K. Macfarlane, M.D., Head, Quality Assurance and Compliance Section, Regulatory Affairs Branch (RAB), Cancer Therapy Evaluation Program (CTEP), Department of Health & Human Services (HHS), Public Health Service, National Institutes of Health (NIH), National Cancer Institute (NCI) sent a 1 page letter and 5 page Memorandum to Burzynski
=======================================
[3] – 10/30/1991 – Dorothy K. Macfarlane, M.D., Head, Quality Assurance and Compliance Section, Regulatory Affairs Branch (RAB), Cancer Therapy Evaluation Program (CTEP), Department of Health & Human Services (HHS), National Institutes of Health (NIH), National Cancer Institute (NCI), sent the 5 page Memorandum re: Review of Brain Tumor Cases Treated With Antineoplastons to 6 doctors
=======================================
======================================
[4] – 10/31/1991 – Michael A. Friedman, M.D. Associate Director, Cancer Therapy Evaluation Program (CTEP), Department of Health & Human Services, National Institutes of Health (NIH), National Cancer Institute (NCI), sent a one page Memorandum to Bruce A. Chabner, M.D., Director, Division of Cancer Treatment, which stated, in part:

“I thought you would be interested in this for several reasons:”

“3. Antineoplastons deserve a closer look”

“It turns out that the agents are well defined, pure chemical entities“
=======================================
=======================================
“The human brain tumor responses are real”

=======================================
[5] – 11/15/1991 – Michael J. Hawkins, M.D., Chief, Investigational Drug Branch, Department of Health & Human Services (HHS), Public Health Service, National Institutes of Health (NIH), National Cancer Institute (NCI), sent a 7 page letter re: Antineoplaston to Decision Network, which stated, in part, on page one:
=======================================
=======================================
“It was the opinion of the site visit team that antitumor activity was documented in this best case series … “

=======================================
[6] – 12/2/1991 – NCI (National Cancer Institute), Decision Network Report on Antineoplastons, states in part, on page 11:
=======================================
=======================================
“The site visit team determined that antitumor activity was documented in this best case series … “

=======================================
[00] – 1991 (12/1991) – the National Cancer Institute (NCI) initiated phase II clinical trials of A10 and AS2-1 (antineoplastons)
=======================================
[7] – 10/20/1993 – Michael A. Friedman, M.D., Associate Director, Cancer Therapy Evaluation Program (CTEP), Division of Cancer Treatment (DCT), National Cancer Institutes (NCI), Department of Health and Human Services (HHS), National Institutes of Health (NIH) sent a 4 page letter to Burzynski, which had on page 4:
=======================================
======================================
“If you are unable or unwilling to provide the antineoplastons in the near future, we will pursue alternative sources to procure the drug or its active components, and will proceed with a clinical development plan to determine whether these chemicals have activity and are beneficial for patients“

=======================================
[8] – 10/26/1993 – Burzynski sent a 5 page letter to Michael A. Friedman, M.D., Associate Director, Cancer Therapy Evaluation Program (CTEP), Division of Cancer Treatment (DCT), National Cancer Institutes (NCI), National Institutes of Health (NIH), which had on page 5
=======================================
======================================
“Your final statements that you are ready to proceed with the treatment with Antineoplastons without our participation caught me by surprise”

“It is hard to imagine that a Federal employee would consider patent infringement, thus infringing on the patent rights of thousands of our shareholders”

——————————————————————
Dr. Michael A. Friedman, please take time away from being a “member of the Nominating Committee” and “director” at Forbes (#Forbes)
——————————————————————
http://www.forbes.com/profile/michael-friedman/
——————————————————————
to let us know how you planned to:

“pursue alternative sources to procure the drug (Antineoplaston) or its active components”

when Burzynski has a patent on some of “its active components” ?

I’m sure your position has nothing to do with the “hack piece” Forbes did on Burzynski where they censored my comments [000]
=======================================
[9] – 11/2/1993 – Michael A. Friedman, M.D., Associate Director, Cancer Therapy Evaluation Program (CTEP), Division of Cancer Treatment (DCT), National Cancer Institute (NCI), Department of Health & Human Services, Public Health Services, National Institutes of Health (NIH), sent a 3 page letter to Burzynski, which had on page 3
=======================================
======================================
“Finally, if even after modifying these studies in accordance with your stated wishes, you are unwilling to supply the antineoplaston materials, please inform me as quickly as possible”

“We will then seek alternative sources of this family of molecules for proper clinical evaluation”

Dr. Michael A. Friedman, please take time away from planning your retirement from “City of Hope”
——————————————————————
http://m.prnewswire.com/news-releases/city-of-hope-names-robert-stone-as-new-chief-executive-officer-192239551.html
——————————————————————
to let us know how you planned to:

” … then seek alternative sources of this (Antineoplaston) family of molecules for proper clinical evaluation”, when Burzynski has a patent on some of “this family of molecules”?
=======================================
[10] – 1/18/1994 – Proposal for Clinical Investigation [2 pgs.]

Phase II Study of Antineoplastons A10 and AS2-1 in Patients with Advanced Recurrent Malignant Astrocytomas

N.C.I. Protocol # T93-0078

Pg. 2

1.0 Protocol Summary – Phase II Study of Antineoplastons A10 and AS2-1 in Patients With Advanced Recurrent Malignant Astrocytomas

1.1 Patient Eligibility

k) Patients with tumors > 5 cm in diameter, multifocal tumors, or with leptomeningeal or with systemic metastases are excluded

1.2 Pretreatment Evaluation

1.3 Treatment Plan

=======================================
[11] – 3/23/1994 – Mario Sznol, M.D., Head, Biologics Evaluation Section, Investigational Drug Branch, Cancer Therapy Evaluation Program (CTEP), Division of Cancer Treatment (DCT), National Cancer Institute (NCI), Department of Health & Human Services (HHS), Public Health Services, National Institutes of Health (NIH), National Cancer Institutes (NCI) sent a 2 page letter to Burzynski requesting to:

1. Lower the Karnofsky performance status (KPS) from 70 to 60

2. Raise the tumor size restriction from 5 cm or less to 8 cm or less

3. Drop the exclusion of multifocal tumors and leptomeningeal spread

=======================================
[12] – 4/19/1994 – Burzynski sent a 2 page letter to Mario Sznol, M.D., Head, Biologics Evaluation Section, Investigational Drug Branch, Cancer Therapy Evaluation Program (CTEP), Division of Cancer Treatment (DCT), National Cancer Institute (NCI), Department of Health & Human Services (HHS), Public Health Services, National Institutes of Health (NIH), National Cancer Institutes (NCI), the it was his opinion that cancer patients with larger tumors should:

1. NOT be included in the protocol intended for patients with smaller tumors receiving less antineoplastons

2. Cancer patients with larger tumors should be accepted in a separate protocol for larger tumors using larger doses of antineoplastons if the existing protocol showed promise

=======================================
[13] – 1/31/1995 – Mark G. Malkin, M.D. sent a one page letter to John L. Lewis, M.D., Chairman, Institutional Review Board (IRB), Memorial Sloan-Kettering Cancer Center (MSKCC) re: T93-0078, RE: Protocol # 93-105, indicating that the National Cancer Institute (NCI) had changed the protocol by:

1. Lowering the Karnofsky Performance Status Score (KPS) from 70% to 60%

2. Removing the exclusion criteria so that there was “no exclusion based on tumor size, multifocality, or leptomeningeal or systemic metastases”

Dr. Mark G. Malkin, the Institutional Principal Investigator, Department of Neurology, Memorial Sloan-Kettering Cancer Center (MSKCC) who sent this letter to Dr. John L. Lewis, the Protocol Chairman, can you take time from your position at the Medical College of Wisconsin
——————————————————————
http://www.mcw.edu/neurology/faculty/MarkMalkin.htm
——————————————————————
and explain why Burzynski was NOT copied on this letter since you knew from his 4/19/1994 response [12] to your 3/23/1994 letter [11] that he did NOT agree to changing the protocol?
=======================================
[14] – 3/29/1995 – Burzynski sent a 2 page letter to Michael A. Friedman, M.D., Associate Director, Cancer Therapy Evaluation Program (CTEP), Division of Cancer Treatment (DCT), National Cancer Institute (NCI), National Institutes of Health (NIH), advising him that he had learned that the protocol had been changed without his knowledge or concurrence by:

1. Lowering the Karnofsky Performance Status score (KPS) from 70% to 60%

2. Changing the eligibility criteria from tumors 5 cm or less to patients with tumors measuring over 5 cm in diameter, multiple tumors, or with leptomeningeal spread or systemic metastases

Dr. Michael A. Friedman, please take time from your Non-Executive Director appointment at Smith & Nephew plc (LSE: SN, NYSE: SNN), the global medical technology business
——————————————————————
http://www.smith-nephew.com/news-and-media/news/michael-a-friedman-md-appointed-non-executive-director/
——————————————————————
and advise why these changes where made to the protocol, when your 3 page letter of 11/2/1993 [9] to Burzynski, advised:

Pg. 1

“[W]e will accede to all the modifications that you have stipulated”

“The changes to made to the protocol are as follows:”

1. “The dose and schedule will be modified exactly as your require”

Pg. 2

5. “The eligibility criteria will be modified to accept only patients with a Karnofsky performance status of 70-100%“

=======================================
[15] – 4/3/1995 – Mario Sznol, M.D., Department of Health and Human Services (HHS), Public Health Services, National Institutes of Health (NIH), National Cancer Institutes (NCI) sent a 2 page letter to Burzynski for Dr. Michael A. Friedman in response to Burzynski’s 3/29/1995 letter [14] advising:

“At the investigator’s request, the amendments to modify the eligibility restrictions for size of tumor, number of tumors, and leptomeningeal spread, and to allow entry of patients with KPS of 60, have been approved“

as if the National Cancer Institute (NCI) had NOT already changed the protocol 1/31/1995 [13]

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[16] – 4/20/1995 – Burzynski sent a 3 page letter to Mario Sznol, M.D., Department of Health and Human Services (HHS), National Institutes of Health (NIH)

=======================================
[17] – 4/26/1995 –

=======================================
[18] – 5/16/1995 – Burzynski sent a 3 page letter to Michael A. Friedman, M.D., Associate Director, Cancer Therapy Evaluation Program (CTEP), Division of Cancer Treatment (DCT), National Cancer Institute (NCI), National Institutes of Health (NIH)

=======================================
[19] – 6/6/1995 – Michael A. Friedman, M.D., Associate Director, Cancer Therapy Evaluation Program (CTEP), Division of Cancer Treatment (DCT), National Cancer Institute (NCI), Department of Health & Human Services (HHS), Public Health Service, National Institutes of Health (NIH), sent a 3 page letter to Burzynski

=======================================
[0000] – 7/27/1995 pg. A17 The Washington Post

In Absentia, Regulators Put on Trial by Critics

‘But researchers who have tried to duplicate Burzynski’s success have been frustrated, said Michael A. Friedman, associate director of the National Cancer Institute’s cancer therapy evaluation program in no small part because Burzynski has refused to cooperate fully”

Dr. Michael A. Friedman
——————————————————————
https://tulane.edu/presidentialsearch/michael-friedman.cfm
——————————————————————
I’m sure that Dr. David H. Gorski a/k/a “Orac” would have something to say about you commenting on a clinical trial before the final results were published, but what do you mean by:

“Burzynski has refused to cooperate fully” ?
=======================================
[20] – 8/18/1995 – CancerNet from the National Cancer Institute (NCI) [2 Pgs.]
Date Last Modified 10/1995

=======================================
[21] – 8/23/1995 – Robert B. Lanman, National Institutes of Health (NIH) Legal Advisor sent a one page letter to Richard A. Jaffe, which advised, in part:

“The NCI does not possess any individual patient records to provide to Dr. Burzynski”

=======================================
[22] – 9/19/1995 – Dr. Michael A. Friedman sent a 2 page letter to Burzynski, which advised, in part, on page 2:

“We have no individual patient records in our possession in addition to the Theradex reports”

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[23] – 10/5/1995 – Robert B. Lanman, National Institutes of Health (NIH) Legal Advisor sent a one page letter to Richard A. Jaffe, which advised, in part:

“With regard to the portion of the medical record which you forwarded, the stamp does indicate that the patient was seen at the National Institutes of Health’s Clinical Center”

“We have learned that 2 patients were enrolled in the Sloan-Kettering study through the Clinical Center and hence, even though the Clinical Center did not have its own protocol, it has medical records for those 2 individuals”

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[24] – 10/27/1995 – Burzynski sent a 7 page letter to Richard Klausner, M.D., Director, National Cancer Institute (NCI), National Institutes of Health (NIH)

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[00] – 1995 (12/1995) – the National Cancer Institute (NCI) initiated phase II clinical trials of A10 and AS2-1 (antineoplastons) from 12/1991 – 12/1995
=======================================
[25] – 1/15/1998 – Robert J. Waldbillig, Ph.D.

Pharmacokinetics of Antineoplaston A10 and AS2-1 in Patients with Neoplastic Disease (2 pgs.)

Pg. 2

Translated into ug/mL from page 22 of 1998 FDA report on ANP

Plasma Antineoplaston Levels in Patients During Treatment

Name of Antineoplaston Ingredient
PG
IsoPG
PN

Plasma Levels (ug/mL)

Mayo Clinic (MC)
302
14 to 35
177

Burzynski
11088
2376
476

Ratio
Burzynski / MC
36 x higher
67-169 x higher
2.7 x higher
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[26] – 2/1999 Volume 74 Number 2 [3 Pgs. – Pg. 137]

Phase II Study of Antineoplastons A10 (NSC 648539) and AS2-1 (NSC 620261) in Patients With Recurrent Glioma

Jan C. Buckner, M.D. (Mayo) Dept.Oncology
Mark G. Malkin, M.D.
Eddie Reed, M.D.
Terrence L. Cascino, M.D.
Joel M. Reid, Ph.D.
Matthew M. Ames, Ph.D.
William P.Y. Tong, Ph.D.
Silam Lam, Ph.D.
William D. Figg, Pharm.D.

Patients with
anaplastic astrocytoma
and
glioblastoma multiforme

=======================================
National Cancer Center (NCI) at the National Institutes of Health (NIH), I do believe this is some of “the data that would back his” (Burzynski’s) “accusations”

Dr. David H. Gorski a/k/a “Orac”, enjoy !
======================================
REFERENCES [A – G]:
======================================
[A] – 4/30/2013 – Eric Merola and Stanislaw Burzynski’s secret weapon against The Skeptics™: Fabio Lanzoni (I kid you not)
——————————————————————
http://scienceblogs.com/insolence/2013/04/30/eric-merola-stanislaw-burzynskis-secret-weapon-against-the-skeptics-fabio-lanzoni/
======================================
[B] – 12/5/2012 – Stanislaw Burzynski: On the arrogance of ignorance about cancer and targeted therapies
——————————————————————
http://scienceblogs.com/insolence/2012/12/05/arrogance-of-ignorance-about-cancer/
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[C] – 9/25/1998 – The Antineoplaston Anomaly: How a Drug Was Used for Decades in Thousands of Patients, With No Safety, Efficacy Data
——————————————————————
http://www.quackwatch.org/01QuackeryRelatedTopics/Cancer/burzynski2.html
——————————————————————
The Cancer Letter, Vol. 24, No. 36, Sept.25, 1998
======================================
[D] – 2/19/2013
——————————————————————
http://m.cancer.gov/topics/CAM/antineoplastons/Patient?print=1
——————————————————————
http://m.cancer.org/treatment/treatmentsandsideeffects/complementaryandalternativemedicine/pharmacologicalandbiologicaltreatment/antineoplaston-therapy
======================================
[E] – 1/14/2013 – The story of Seán Ó’Laighin, patient of Dr. Stanislaw Burzynski
——————————————————————
http://scienceblogs.com/insolence/2013/01/14/the-story-of-sean-olaighin-patient-of-dr-stanislaw-burzynski/
======================================
[F] – 6/23/2013 – QUESTIONS the Critics and Cynics, “The Skeptics™” do NOT want to ANSWER:
——————————————————————
https://stanislawrajmundburzynski.wordpress.com/2013/06/23/questions-the-critics-and-cynics-the-skeptics-do-not-want-to-answer/
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[G] – 3/20/2013 – David Gorski (@gorskon) tweeted at 12:44pm – 30 Mar 13:
======================================
=======================================
REFERENCES:
=======================================
1] – 1991 (10/4/1991) – Site visit – Antineoplaston Cases:
——————————————————————
https://stanislawrajmundburzynski.wordpress.com/2013/09/17/1-1991-1041991-site-visit-antineoplaston-cases/
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[2] – 1991 (10/30/1991) – Dr. Dorothy K. Macfarlane letter to Burzynski:
——————————————————————
https://stanislawrajmundburzynski.wordpress.com/2013/09/17/2-1991-10301991-dr-dorothy-k-macfarlane-letter-to-burzynski/
=======================================
[3] – 1991 (10/30/1991) – Dr. Dorothy K. Macfarlane Memorandum – 10/4/1991 – site visit (5 pgs.):
——————————————————————
https://stanislawrajmundburzynski.wordpress.com/2013/09/17/3-1991-10301991-dr-dorothy-k-macfarlane-memorandum-1041991-site-visit-5-pgs/
=======================================
[4] – 1991 (10/31/1991) – Dr. Michael A. Friedman Memorandum to Dr. Bruce A. Chabner (1 pg.):
——————————————————————
https://stanislawrajmundburzynski.wordpress.com/2013/09/17/4-1991-10311991-dr-michael-a-friedman-memorandum-to-dr-bruce-a-chabner-1-pg/
=======================================
[5] – 1991 (11/15/1991) – Dr. Michael J. Hawkins to Decision Network:
——————————————————————
https://stanislawrajmundburzynski.wordpress.com/2013/09/17/5-1991-11151991-dr-michael-j-hawkins-to-decision-network/
=======================================
[6] – 1991 (12/2/1991) – NCI Decision Network Report on Antineoplastons:
——————————————————————
https://stanislawrajmundburzynski.wordpress.com/2013/09/17/6-1991-12291-nci-decision-network-report-on-antineoplastons/
=======================================
[00] – 1991 (12/1991) – Burzynski: Managing social conflict in complementary and alternative medicine research: the case of antineoplastons:
——————————————————————
https://stanislawrajmundburzynski.wordpress.com/2013/04/26/burzynski-managing-social-conflict-in-complementary-and-alternative-medicine-research-the-case-of-antineoplastons/
=======================================
[7] – 1993 (10/20/1993) – Dr. Michael A. Friedman to Burzynski (4 pgs.):
——————————————————————
https://stanislawrajmundburzynski.wordpress.com/2013/09/17/7-1993-10201993-dr-michael-a-friedman-to-burzynski-4-pgs/
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[8] – 1993 (10/26/1993) – Burzynski to Dr. Michael A. Friedman:
——————————————————————
https://stanislawrajmundburzynski.wordpress.com/2013/09/17/8-1993-10261993-burzynski-to-dr-michael-a-friedman/
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[000] – Dr. Peter A. Lipson (and / or his Censor(s)) is a Coward: Critiquing “A Film Producer, A Cancer Doctor, And Their Critics”:
——————————————————————
https://stanislawrajmundburzynski.wordpress.com/2013/04/26/dr-peter-a-lipson-and-or-his-censors-is-a-coward-critiquing-a-film-producer-a-cancer-doctor-and-their-critics/
=======================================
[9] – 1993 (11/2/1993) – Dr. Michael A. Friedman to Burzynski:
——————————————————————
https://stanislawrajmundburzynski.wordpress.com/2013/09/18/9-1993-1121993-dr-michael-a-friedman-to-burzynski/
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[10] – 1994 (1/18/1994) – Proposal for Clinical Investigation (2 pgs.):
——————————————————————
https://stanislawrajmundburzynski.wordpress.com/2013/09/18/10-1994-1181994-proposal-for-clinical-investigation-2-pgs/
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[11] – 1994 (3/23/1994) – Dr. Mario Sznol to Burzynski [2 pgs.]:
——————————————————————
https://stanislawrajmundburzynski.wordpress.com/2013/09/18/11-1994-3231994-dr-mario-sznol-to-burzynski-2-pgs/
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[12] – 1994 (4/19/1994) – Burzynski to Dr. Mario Sznol [2 Pgs.]:
——————————————————————
https://stanislawrajmundburzynski.wordpress.com/2013/09/18/12-1994-4191994-burzynski-to-dr-mario-sznol-2-pgs/
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[13] – 1995 (1/31/1995) – Dr. Mark G. Malkin to Dr. John L. Lewis (1 pg.):
——————————————————————
https://stanislawrajmundburzynski.wordpress.com/2013/09/18/13-1995-1311995-dr-mark-g-malkin-to-dr-john-l-lewis-1-pg/
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[14] – 1995 (3/29/1995) – Burzynski to Dr. Michael A. Friedman (2 pgs.):
——————————————————————
https://stanislawrajmundburzynski.wordpress.com/2013/09/18/14-1995-3291995-burzynski-to-dr-michael-a-friedman-2-pgs/
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[15] – 1995 (4/3/1995) – Dr. Mario Sznol to Burzynski:
——————————————————————
https://stanislawrajmundburzynski.wordpress.com/2013/09/18/15-1995-431995-dr-mario-sznol-to-burzynski/
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[16] – 1995 (4/20/1995) – Burzynski to Dr. Mario Sznol;
——————————————————————
https://stanislawrajmundburzynski.wordpress.com/2013/09/18/16-1995-4201995-burzynski-to-dr-mario-sznol/
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[17] – 1995 (4/26/1995) (Pg. 3):
——————————————————————
https://stanislawrajmundburzynski.wordpress.com/2013/09/18/17-1995-4261995-pg-3/
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[18] – 1995 (5/16/1995) – Burzynski to Dr. Michael A. Friedman:
——————————————————————
https://stanislawrajmundburzynski.wordpress.com/2013/09/18/18-1995-5161995-burzynski-to-dr-michael-a-friedman/
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[19] – 1995 (6/6/1995) Dr. Michael A. Friedman to Burzynski (3 pgs.):
——————————————————————
https://stanislawrajmundburzynski.wordpress.com/2013/09/18/19-1995-661995-dr-michael-a-friedman-to-burzynski-3-pgs/
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[0000] – 7/27/1995 – 1 pg.
——————————————————————

Click to access Scqd59b00.pdf

——————————————————————
2 pgs.
——————————————————————

Click to access Syiw77d00.pdf

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[20] – 1995 (8/18/1995) – CancerNet from the National Cancer Institute (2 pgs.): CANCER FACTS
National Cancer Institute • National Institutes of Health Department of Health and Human Services, Antineoplastons, pg. 1
——————————————————————
https://stanislawrajmundburzynski.wordpress.com/2013/09/18/20-1995-8181995-cancernet-from-the-national-cancer-institute-2-pgs/
=======================================
=======================================
“The reviewers of this series found evidence of antitumor activity … “

=======================================
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[21] – 1995 (8/23/1995) – Robert B. Lanman to Burzynski (1 Pg.):
——————————————————————
https://stanislawrajmundburzynski.wordpress.com/2013/09/18/21-1995-8231995-robert-b-lanman-to-burzynski-1-pg/
=======================================
[22] – 1995 (9/19/1995) – Dr. Michael A. Friedman to Burzynski (2 pgs.):]
——————————————————————
https://stanislawrajmundburzynski.wordpress.com/2013/09/18/22-1995-9191995-dr-michael-a-friedman-to-burzynski-2-pgs/
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[23] – 1995 (10/5/1995) – Robert B. Lanman to Burzynski (1 pg.):
——————————————————————
https://stanislawrajmundburzynski.wordpress.com/2013/09/18/23-1995-1051995-robert-b-lanman-to-burzynski-1-pg/
=======================================
[24] – 1995 (10/27/1995) – Burzynski to Dr. Richard Klausner (7 pgs.):
——————————————————————
https://stanislawrajmundburzynski.wordpress.com/2013/09/18/24-1995-10271995-burzynski-to-dr-richard-klausner-7-pgs/
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