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

20130920-130106.jpg

20130920-130305.jpg

20130920-130429.jpg

20130920-130547.jpg
======================================
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
======================================

[16] – 1995 (4/20/1995) – Burzynski to Dr. Mario Sznol

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/
======================================
[16] – 1995 (4/20/1995) – Burzynski to Dr. Mario Sznol
——————————————————————
Mario Sznol, M.D., Department of Health and Human Services, National Institutes of Health

Dear Dr. Sznol,

Your letter of 4/3/1995

(copy attached)

does not provide adequate justification for the changes in the protocol for

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

Let me make perfectly clear that, as the discoverer and developer of antineoplastons and the individual with nearly 20 years clinical experience using them, it is my professional opinion that the drugs will not produce substantial benefit in such advanced patients

The current protocol has had success only in patients who have tumors not exceeding 5 cm in diameter and who do not have multiple tumors or leptomeningeal or systemic metastases

As the Senior Investigator of NCI requested, patients should have Karnofsky Performance Status of not lower than 70%

(letter attached)

As I have repeatedly informed you, it is exactly because of the current protocol’s failure to benefit advanced patients that we developed new and more aggressive protocols for such advanced tumors, for example, provides antineoplaston A10 in doses 3 times greater than that specified in the protocol currently being used

In order to make such dosing possible, we are using a much higher concentration of A10 — 300mg/mL instead of 80mg/mL

The dosing schedule being used for such advanced tumors is also quite different

Instead of injections of each antineoplaston every 30 minutes, patients receive a much greater amount every 4 hours

Pg. 2

The acceptance of very advanced brain tumor patients to the current protocol would be highly unethical because there is no realistic chance they will have a meaningful response

The list attached to your letter of 4/3/1995 (enclosed), proves my observation that patients who had tumors substantially larger than 5 cm do not respond well under the current protocol

There were only 2 such patients, with the largest tumor diameter corresponding to 5.5 and. 6.5 cm

Both had less than 50% decrease in the size of their tumors

According to the existing protocol, patients should have more than a 50% decrease in tumor size to be classified as responders

Please bear in mind that the point of this trial is not to prove once again that this protocol does not work in patients with very large tumors, multifocal tumors, and low Karnofsky scores

We have already established this fact

Moreover, the informed consent form as currently written falsely implies that the discoverer of antineoplastons believes such advanced patients may benefit substantially from the current protocol

In fact, I have specifically informed you on several occasions that I do not believe advanced patients will obtain substantial benefit

Please be forewarned that you may face legal liability resulting from these unethical misrepresentations

We are anxiously awaiting the complete data on the 1st 5 patients as promised in your letter of 4/3/1995

Based on the limited information received from Theradex on the 1st 7 cases, we have reason to believe that the protocol has been violated in every case

5 cases have been accepted in violation of inclusion criteria

Due to interruptions in the treatment schedule and the time necessary to escalate the dosage, one of these patients received less than 3 weeks of full dose treatment

Such duration of treatment was not sufficient to show the effectiveness of the therapy

Finally, 2 additional patients were removed from the study and said to have progression of disease when in fact no progression was documented

One of these patients, #4369975, underwent tumor resection 3 weeks after discontinuation of the treatment with antineoplastons

Microscopic examination of the tumor specimen confirmed absence of viable tumor cells

It is clear that what was classified as tumor progression corresponded to extensive necrosis or tumor death

What I thought was especially inexcusable and unethical is that the 30 year old patient #196370, who clearly did not have progression of the tumor, was removed from the study against the criteria for removal listed in the protocol

This patients died a few months later
I strongly believe that if the patient had continued the treatment under the protocol, his life would have been saved

Attached to this letter, you will find a list of

Pg. 3

violations of the protocol

Based on these violations, it is clear that the current investigators are unable to conduct this study under the current protocol

I hereby request that:

1) The National Cancer Institute immediately terminate the current investigators and appoint mew investigators at different medical institutions acceptable to Burzynski Research Institute

2) Patient accrual must cease until such investigators and institutions are appointed

Until you appoint the new investigators, I will provide free treatment and medical care under my supervision as long as necessary to the patients currently being treated under the protocol

SRB/cf

Enclosure

cc:

Senator Joseph Biden
Senator Barbara Boxer
Senator Diane Feinstein
Senator Tom Harkin
Senator Barbara Mikulski
Congressman Berkly Bedell
Congresswoman Nancy Pelosi
Dr. Jan Buckner
Dr. Daniel Eskinazi
Dr. Michael Friedman
Dr. Jay Greenblatt
Mr. Richard Jaffe
Dr. Mark Malkin
Ms. Mary McCabe
Dr. Ralph Moss
Dr. David Parkinson
Ms. Dorothy Tisevich
Mr. Frank Wiewel
——————————————————————

======================================
1995 (4/20/1995) – Burzynski to [14]
1995 (4/20/1995) – Burzynski to [15] (3 pgs.)
1995 (4/3/1995) – Dr. Mario Sznol to Burzynski
======================================

[12] – 1994 (4/19/1994) – Burzynski to Dr. Mario Sznol [2 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/
======================================
[12] – 1994 (4/19/1994) – Burzynski to Dr. Mario Sznol [2 Pgs.]
——————————————————————
Mario Sznol, M.D., Head, Biologics Evaluation Section, Investigational Drug Branch, CTEP, DCT, National Cancer Institute

Dear Dr. Sznol,

I am glad to learn from your letter of 3/23/1994 that some patients have already been enrolled in the NCI-sponsored trials of Antineoplastons and there is a strong interest of the NCI and the Investigators to broaden the study

While I think that, ultimately, Antineoplastons would prove useful in the treatment of more advanced cases of malignant brain tumors, I think that to expand the trials now through admission of such difficult cases is premature

The 1st stage of the studies which are currently in progress should be completed in order to have the most accurate preliminary evaluation of anticancer activity

I sincerely hope that the Investigators conducting the study will report good results in the treatment of at least some of the initial 15 patients involved in stage I

However, if the reverse is true, then it won’t make any sense to conduct trials in very advanced cases if less advanced cases do not respond

I would expect that there would be a significant difference in response between the patients admitted under current acceptance criteria and the expanded eligibility criteria proposed in your letter of 3/23/1994

Therefore, I think that such patients should be involved in a separate trial for large and multifocal tumors, and treated and evaluated according to a modified protocol

SRB/cf

cc:

David Parkinson, M.D.
Mike Friedman, M.D.
Dale Shoemaker, Ph.D.
Jay Greenblatt, Ph.D.
Dean Mouscher, BRI
Mary McCabe, R.N.
Samuel Broder, M.D.
Bruce Chabner, M.D.
——————————————————————

======================================
1994 (3/23/1994) – Dr. Mario Sznol to Burzynski
1994 (4/19/1994) – Burzynski to Dr. Mario Sznol [20] (2 pgs.)
======================================

[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
======================================