Burzynski: Why has the FDA NOT granted Accelerated Approval for Antineoplastons A10 (Atengenal) and AS2-1 (Astugenal) ?

======================================
1996 – Accelerated approval started by United States Food and Drug Administration Commissioner, Dr. David A. Kessler
(.4:18 – .6:10):

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Tamoxifen:
======================================
7/1997 – A phase I study of high-dose tamoxifen for the treatment of refractory malignant GLIOMAS OF CHILDHOOD
http://www.ncbi.nlm.nih.gov/pubmed/9815790/
Clin Cancer Res. 1997 Jul;3(7):1109-15
http://www.ncbi.nlm.nih.gov/m/pubmed/9815790/
Clin Cancer Res July 1997 3; 1109
http://m.clincancerres.aacrjournals.org/content/3/7/1109.full.pd
Departments of Neurosurgery, Children’s Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA

http://clincancerres.aacrjournals.org/content/3/7/1109
Children with malignant GLIOMAS THAT PROGRESSED AFTER CONVENTIONAL THERAPY
——————————————————————
0 / 0% – EXHIBITED CLEAR-CUT TUMOR regression
——————————————————————
17 months (1 year 5 months) – longest survivor lived for after beginning tamoxifen
======================================
2000 – Radiation therapy and high-dose tamoxifen in the treatment of patients with diffuse BRAINSTEM GLIOMAS:

results of a Brazilian cooperative study
http://www.ncbi.nlm.nih.gov/pubmed/10715294/
Brainstem Glioma Cooperative Group
http://www.ncbi.nlm.nih.gov/m/pubmed/10715294/
J Clin Oncol 18, 1246-1253
http://m.jco.ascopubs.org/content/18/6/1246.long
——————————————————————
22 – assessable patients
——————————————————————
10.3 months – Median Survival
——————————————————————
4 / 18% – remain alive without tumoral progression
——————————————————————
8 / 37.0% {+/- 2 / 9.5%} (mean +/- SD) – 1-year Survival rate
——————————————————————
treatment combination PRODUCED NO SIGNIFICANT CHANGE in overall POOR prognosis of patients

Most tumors responded initially to treatment but recurred as study progressed

Based on POOR RESULTS, recommend ALTERNATIVE TREATMENTS be tested in patients with this type of tumor
======================================
Temodar (Temozolomide):
======================================
Temozolomide received accelerated approval by the U.S. Food and Drug Administration 1/1999 for treatment of ANAPLASTIC ASTROCYTOMA (brain cancer) patients
——————————————————————
54 patients
——————————————————————
12 / 22% – response rate
——————————————————————
5 / 9% – Complete Response rate
——————————————————————
50 weeks (16-114 weeks) – Median duration of all responses
——————————————————————
64 weeks (52-114 weeks) – Median duration of Complete Response
——————————————————————
4.4 months – Median Progression-Free Survival
——————————————————————
15.9 months (1 year 3.9 months) – Median Overall Survival
——————————————————————
At time of approval, NO RESULTS were available from randomized controlled trials in refractory ANAPLASTIC ASTROCYTOMA that show clinical benefit such as improvement in disease-related symptoms or prolonged survival
——————————————————————
http://clincancerres.aacrjournals.org/content/11/19/6767.full
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Was the United States Food and Drug Administration’s 1/1999 accelerated approval based on the PUBLISHED FINAL RESULTS OF A PHASE II (2) CLINICAL TRIAL?
======================================
12/2000 – Temozolomide and ANAPLASTIC ASTROCYTOMA:

new indication

NO CLEAR PROOF OF EFFICACY
http://www.ncbi.nlm.nih.gov/pubmed/11475493/
Prescrire Int. 2000 Dec;9(50):170-1.
http://www.ncbi.nlm.nih.gov/m/pubmed/11475493/
(1) Temozolomide recently licensed in France for treating patients with ANAPLASTIC ASTROCYTOMA who are in relapse or progression after standard therapy
——————————————————————
(2) clinical dossier contains only one non comparative trial
——————————————————————
(3) 111 patients with ANAPLASTIC ASTROCYTOMA or oligoanaplastic astrocytoma had not all had the standard treatment with surgery, radiotherapy and chemotherapy
——————————————————————
54 patients – subgroup who met criteria
——————————————————————
16 months (1 year 4 months) – Median Global Survival
——————————————————————
31 months (2 years 7 months) – Median Global Survival from start of initial treatment
——————————————————————
NO BETTER THAN SURVIVAL BEFORE THE INTRODUCTION OF temozolomide
======================================
The answer is: NO

1/1999 – FDA Accelerated Approval
9/1999 – Phase 2 publication
======================================
9/1999 – Multicenter phase II trial of temozolomide in patients with ANAPLASTIC ASTROCYTOMA or anaplastic oligoastrocytoma at first relapse

Temodal Brain Tumor Group
http://www.ncbi.nlm.nih.gov/pubmed/10561351/
J Clin Oncol. 1999 Sep;17(9):2762-71.
http://www.ncbi.nlm.nih.gov/m/pubmed/10561351/
University of Texas M.D. Anderson Cancer Center, Houston, TX, USA
======================================
http://www.drugs.com/pro/temodar.html
======================================
http://www.pharmainfo.net/fda-articles/fda-safety-page-fatal-medication-errors-associated-temodar
======================================
TEMODAR ADVERSE EVENTS REPORTED TO THE FDA OVER TIME:
http://www.drugcite.com/?q=TEMODAR
======================================
ADVERSE EVENTS:
Primary Suspect Reports: 4,436
Total Reports: 6,350
http://www.adverseevents.com/drugdetail.php?AEDrugID=1794&BrandName=TEMODAR
======================================
http://www.temodar.com/temodar/index.do
======================================
2004 – Supratentorial high-grade ASTROCYTOMA and DIFFUSE BRAINSTEM GLIOMA:

two challenges for the pediatric oncologist
http://www.ncbi.nlm.nih.gov/pubmed/15047924/
Oncologist. 2004;9(2):197-206.
http://www.ncbi.nlm.nih.gov/m/pubmed/15047924/
Oncologist 9, 197-206
http://m.theoncologist.alphamedpress.org/content/9/2/197.long
Division of Neuro-Oncology, Department of Hematology-Oncology, St. Jude Children’s Research Hospital, Memphis, Tennessee, USA

neoplasms predominantly involve supratentorial hemispheres or pons, in which case tumors are usually called DIFFUSE BRAINSTEM GLIOMAS

supratentorial neoplasms
——————————————————————
diagnosis of DIFFUSE BRAINSTEM GLIOMA based upon typical imaging, dispensing with need for surgery in majority of cases

Radiation therapy is mainstay of treatment for children with DIFFUSE BRAINSTEM GLIOMAS
——————————————————————
2 years – Less than 10% of children with diffuse brainstem gliomas survive
——————————————————————
outcome for patients with either type of tumor is POOR when standard multimodality therapy is used

children are ideal candidates for INNOVATIVE TREATMENT approaches
——————————————————————
3-21 years Patients were eligible for current multiinstitutional study
——————————————————————
33 patients (6.4 years – Median age at diagnosis) enrolled
——————————————————————
33 / 100% – DIED OF DISEASE PROGRESSION
——————————————————————
12 months (1 year) – Median Survival
——————————————————————
16 / 48% – estimated 1-year Survival rate (standard error, 1 / 8%)
——————————————————————
administration of temozolomide after RT DIDN’T ALTER POOR PROGNOSIS associated with newly diagnosed diffuse BRAINSTEM GLIOMA in children
======================================
1/1/2005 (11/24/2004) – Role of temozolomide after radiotherapy for newly diagnosed diffuse BRAINSTEM GLIOMA in children:

results of a multiinstitutional study (SJHG-98)
http://www.ncbi.nlm.nih.gov/pubmed/15565574
Cancer. 2005 Jan 1;103(1):133-9.
http://www.ncbi.nlm.nih.gov/m/pubmed/15565574
Cancer 103, 133-139
http://onlinelibrary.wiley.com/doi/10.1002/cncr.20741/abstract;jsessionid=6717837591CCC8FCBD8E46163808E221.d03t01
Cancer
Volume 103, Issue 1, pages 133–139, 1 January 2005
http://onlinelibrary.wiley.com/doi/10.1002/cncr.20741/full
Article first published online: 24 NOV 2004
References:
http://onlinelibrary.wiley.com/doi/10.1002/cncr.20741/references
Cited By:
http://onlinelibrary.wiley.com/doi/10.1002/cncr.20741/citedby
DOI: 10.1002/cncr.20741

Department of Hematology-Oncology, St. Jude Children’s Research Hospital, Memphis, Tennessee, USA
——————————————————————
33 patients: (33 / 100% – 6.4 years: Median age)
——————————————————————
33 / 100% – ALL DIED OF DISEASE PROGRESSION
——————————————————————
12 months (1 year) – Median Survival
——————————————————————
16 / 48% – 1 year estimated Survival rate
——————————————————————
Table 1. Results of radiation therapy in combination with chemotherapy for newly diagnosed, diffuse, intrinsic BRAIN STEM GLIOMA

Author
Study Type
Patients Total No.
Treatment Radiation Therapy
Additional Chemotherapy
Efficacy
OS MST CR PR SD PD

Multiinstitutional 33 56 Temozolomide, irinotecan 0 0 12 NA NA NA

response rates based on evaluable patients
32 54 Topotecan

CR – complete response
GCSF – granulocyte colony stimulating factor
HD – high dose tamoxifen
HDB – high dose chemotherapy and autologous bone marrow transplantation HF – hyperfractionated
M – months
MST – median survival time
NA – not available
OS – overall survival
PD – progressive disease
PR – partial response
SD – stable disease
UNK – unknown
* 1 patient had radiological improvement

Cancer 103, 133-139
——————————————————————
3-21 years – eligible for current multiinstitutional study
——————————————————————
33 – (Median age at diagnosis
6.4 years) enrolled
——————————————————————
ALL PATIENTS DIED OF DISEASE PROGRESSION
——————————————————————
12 months (1 year) – Median Survival
——————————————————————
48% – estimated 1-year Survival rate (standard error 8%)
——————————————————————
administration of temozolomide after RT DIDN’T ALTER POOR PROGNOSIS associated with newly diagnosed diffuse BRAINSTEM GLIOMA in children
======================================
2/2008 (2/2/2007)
Treatment of children with diffuse intrinsic BRAIN STEM GLIOMA
with radiotherapy, vincristine and oral VP-16:

a Children’s Oncology Group phase II study
http://www.ncbi.nlm.nih.gov/pubmed/17278121
Pediatr Blood Cancer. 2008 Feb;50(2):227-30
http://www.ncbi.nlm.nih.gov/m/pubmed/17278121
University of Rochester Medical Center, Rochester, New York, USA.

http://onlinelibrary.wiley.com/doi/10.1002/pbc.21154/abstract;jsessionid=DE7A67EFBAC1A184F6805F11CFC4F30B.d02t02
Article first published online: 2 FEB 2007
DOI: 10.1002/pbc.21154

prognosis for children with BRAIN STEM GLIOMA remains grim

The Pediatric Oncology Group (POG, now part of Children’s Oncology Group) conducted study using agents in combination with standard external beam radiation for children with newly diagnosed BRAIN STEM GLIOMA
——————————————————————
Children eligible
3-21 years of age, had MRI-evidence of diffuse intrinsic pontine glioma, and had neurologic deficits of <6 months duration
——————————————————————
30 eligible and evaluable for Survival / toxicity
——————————————————————
8 years (3-14 years) – Median age
——————————————————————
7 / 23% – Partial Response following radiation
18 / 60% – Stable Disease
2 / 7% – Progressive Disease
3 / 10% – Response Not measured
——————————————————————
30 / 100% CHILDREN DIED
——————————————————————
Overall Survival 1 year
27 +/- 7%
2 years, 3 +/- 2%
——————————————————————
9 months (3-36 months) – Median Survival
——————————————————————
addition of vincristine and oral VP-16 to standard external beam radiation causes moderate toxicity and DOESN’T IMPROVE SURVIVAL OF CHILDREN WITH DIFFUSE INTRINSIC BRAIN STEM GLIOMA
======================================
Avastin (Bevacizumab):
======================================
5/6/2009 – U.S. Food and Drug Administration (FDA) granted accelerated approval of Avastin (bevacizumab) for people with GLIOBLASTOMA (brain cancer) with progressive disease following prior therapy

effectiveness of Avastin in AGGRESSIVE form of BRAIN CANCER based on improvement in objective response rate

Currently, NO DATA available from randomized controlled trials demonstrating improvement in disease-related symptoms or increased survival with Avastin in GLIOBLASTOMA
——————————————————————
11.3 months – Progression-Free Survival
——————————————————————
http://www.drugs.com/newdrugs/fda-grants-accelerated-approval-avastin-combination-paclitaxel-chemotherapy-first-line-advanced-852.html
According to FDA analysis of study

Study AVF3708g
——————————————————————
22 / 26% – tumor responses observed of 85 patients treated with Avastin alone
——————————————————————
4.2 months – Median duration of response in patients
——————————————————————
Study NCI 06-C-0064E

Efficacy of Avastin in GLIOBLASTOMA that progressed following prior therapy supported by another study that used same response assessment criteria as AVF3708g

56 patients treated with Avastin alone
——————————————————————
11 / 20% of patients – Responses were observed
——————————————————————
3.9 months – Median duration of response
——————————————————————
http://www.cancer.gov/cancertopics/druginfo/fda-bevacizumab
FDA – “People with this type of brain cancer have had no new treatments in more than a decade”
http://www.drugs.com/newdrugs/fda-grants-accelerated-approval-avastin-brain-cancer-glioblastoma-has-progressed-following-prior-1342.html
——————————————————————
Avastin is gene-targeted therapy, which can only target certain specific genes
======================================
Afinitor (Everolimus):
======================================
Afinitor (ubependymal giant cell ASTROCYTOMA (SEGA) brain tumor)
——————————————————————
10/29/2010 – FDA granted accelerated approval for Afinitor after single Phase 2 study of only 28 patients
——————————————————————
32% experienced 50% reduction of tumor
——————————————————————
none of their tumors went away completely
======================================
Was the United States Food and Drug Administration’s 10/29/2010 accelerated approval based on the PUBLISHED FINAL RESULTS OF A PHASE II (2) CLINICAL TRIAL?
======================================
10/12/2011 (8/1/2011) – Everolimus tablets for patients with subependymal giant cell ASTROCYTOMA
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3389821/
Expert Opin Pharmacother. Author manuscript; available in PMC 2012 July 5.
Published in final edited form as:
Expert Opin Pharmacother. 2011 October; 12(14): 2265–2269.
Published online 2011 August 1. doi: 10.1517/14656566.2011.601742
PMCID: PMC3389821
NIHMSID: NIHMS385824
——————————————————————
http://www.fda.gov/AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/CDER/ucm231967.htm
======================================
The answer is: NO

10/29/2010 – FDA Accelerated Approval
10/12/2011 – publication
� � � � � � � � � � � � � � � � �
COMPARE COMBINED:
� � � � � � � � � � � � � � � � �
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ANAPLASTIC ASTROCYTOMA
==========================
22% – Objective Response: Objective response = complete response and partial response – Antineoplastons

22% – response rate: Temodar
——————————————————————
11% – Complete Response: Antineoplastons

9% – Complete Response rate: Temodar
——————————————————————
17+ years – Maximum Survival : patient with ANAPLASTIC ASTROCYTOMA – Antineoplastons

50 weeks (16-114 weeks) – Median duration of all responses: Temodar
——————————————————————
17+ years – Maximum Survival : patient with ANAPLASTIC ASTROCYTOMA – Antineoplastons

64 weeks (52-114 weeks) – Median duration of Complete Response: Temodar
——————————————————————
6 months – 7 / 39% Progression-Free Survival: Antineoplastons

4.4 months – Median Progression-Free Survival: Temodar
——————————————————————
5 years – 4 / 22% Overall Survival: Antineoplastons

2 years – 7 / 39% Overall Survival: Antineoplastons

2 years – Most patients with brainstem glioma fail standard radiation therapy and chemotherapy and do not survive longer

15.9 months (1 year 3.9 months) – Median Overall Survival: Temodar
� � � � � � � � � � � � � � � � �
COMPARE COMBINED:
� � � � � � � � � � � � � � � � �
======================================
GLIOBLASTOMA
======================================
39% – Progression-Free Survival (PFS) at 6 months: Antineoplastons

5.28 months – Median Progression-Free Survival (PFS): Antineoplastons

11.3 months – Progression-Free Survival: Avastin
——————————————————————
32% – % of Patients Showing Objective Response = complete response and partial response: Antineoplastons

26% – tumor responses observed Avastin
——————————————————————
42% – special exception (SE): Overall survival (OS) – 2 years: Antineoplastons

36% – BT-11: Overall survival (OS) – 2 years: Antineoplastons

19% – special exception (SE): Overall survival (OS) – 5 years: Antineoplastons

25% – BT-11: Overall survival (OS) – 5 years: Antineoplastons

4.2 months – Median duration of response in patients: Avastin
——————————————————————
9 / 32% – # and % of Patients Showing Objective response = complete response and partial response – Antineoplastons

11 / 20% of patients – Responses were observed: Avastin
——————————————————————
5+ years – Maximum Survival : patient with GLIOBLASTOMA – Antineoplastons

3.9 months – Median duration of response: Avastin
� � � � � � � � � � � � � � � � �
COMPARE COMBINED:
� � � � � � � � � � � � � � � � �
======================================
ASTROCYTOMA
======================================
47% / 7 – % and # of Patients Showing Objective response = complete response (6) and partial response (1) – Antineoplastons

32% experienced 50% reduction of tumor – Afinitor
� � � � � � � � � � � � � � � � �
Burzynski: Complete Response, Partial Response, Stable Disease, Progressive Disease, Objective Response, and Response:
https://stanislawrajmundburzynski.wordpress.com/2013/07/04/burzynski-complete-response-partial-response-stable-disease-progressive-disease-objective-response-and-response/
� � � � � � � � � � � � � � � � �
Burzynski: Progression-Free Survival:
https://stanislawrajmundburzynski.wordpress.com/2013/07/04/burzynski-progression-free-survival/
� � � � � � � � � � � � � � � � �
WHAT IS MISDIRECTION ? Critiquing “Antineoplastons: Has the FDA kept its promise to the American people ?”:
https://stanislawrajmundburzynski.wordpress.com/2013/06/08/what-is-misdirection-critiquing-antineoplastons-has-the-fda-kept-its-promise-to-the-american-people/
� � � � � � � � � � � � � � � � �

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Critiquing: In which Orac does Stanislaw Burzynski propagandist Eric Merola a favor…

“Orac” / Dr. David H. Gorski posted his lame 6/3/2013 excuse for a review of Burzynski: Cancer Is Serious Business, Part II (2), and I critiqued it:

Critiquing: In which the latest movie about Stanislaw Burzynski “cancer cure” is reviewed…with Insolence:
https://stanislawrajmundburzynski.wordpress.com/2013/07/18/critiquing-in-which-the-latest-movie-about-stanislaw-burzynski-cancer-cure-is-reviewed-with-insolence-2/
7/17/2013 Gorski pushed out his “best” effort:

In which Orac does Stanislaw Burzynski propagandist Eric Merola a favor…
http://scienceblogs.com/insolence/2013/07/17/in-which-orac-does-stanislaw-burzynski-propagandist-eric-merola-a-favor/
After my Epic Sharknado Deconstruction of “Orac’s” “review,” I thought it only fair to continue the feeding frenzy with a Burzynski Texas Tornado

Believe it or not, I’m going to do “Dr.” Gorski (who particularly likes me, to the point of thinking, apparently, that I’m a white research supremacist) a favor

“Dr.” Gorski, as you recall, is a supposed “Doctor,” oncologist, breast cancer specialist, cancer (cough-cough) “researcher” who was responsible for two dubious propaganda reviews about documentary films which Eric Merola made re: Stanislaw Burzynski, the cancer doctor who has used “antineoplastons” to treat cancer without having published any final clinical trial evidence that they do what he claims, since his 1st completed phase II (2) clinical trial in 2009

However, no worries

M. D. Anderson did a clinical trial in 2006 and did NOT publish the final results until 6-7 years later, 2/13/2013

Based on that criteria, Burzynski has until 2016-2017 to publish

Back in 2010, Merola released the first of a dynamic duo of films, the first of which was called Burzynski The Movie: Cancer Is A Serious Business (as Gorski likes to call it, by adding an “A” in the title)

The sequel, the slightly less pretentiously titled Burzynski: Cancer Is A Serious Business, Part 2 (as Gorski again likes to call it with the “A”), was then released June 1 on various pay-per-view modes

As has been pointed out, it’s better than the first, and it features direct attacks on The Skeptics™, or SkeptiCowards©, if you will, who had the temerity to criticize Burzynski and Merola over the last couple of years with their school-yard bully attacks, NOT having the intestinal testicular fortitude to back up their claims with any citation(s), reference(s), and / or link(s) in support of their blatherskite, which they found worthy enough to defend on my blog

Merola is apparently trying to recreate the success of his previous strategy, which involved letting people watch the movie online for free for limited periods of time on websites like Mercola.com

I link directly to the Mercola.com link to the second Burzynski movie, because I want to give Mercola more Google juice than he already has

The movie was, however, on Vimeo until July 20:

BURZYNSKI: CANCER IS SERIOUS BUSINESS, PART II (2013) from BurzynskiMovie on Vimeo
http://articles.mercola.com/sites/articles/archive/2013/07/13/burzynski-cancer-film.aspx
If you want to see what the fuss was about and whether my criticisms of The Skeptics™, or SkeptiCowards©, were valid, now’s your chance

If you want to see the highlighted attack on The Skeptics™ SkeptiCowards©, it begins around 1:19 h into the movie

Yes, I’m encouraging you to watch Burzynski 2

It’s a beautiful example of all the things that Gorski tried to inculcate #TAM2013 attendees against

Indeed, dissecting this magnum opus is an excellent way to teach oneself critical thinking, much as dissecting creationist tripe is

Unfortunately, Gorski is unable to do this, because individuals like me, exist and will NOT let him get away with his disingenuous hack attacks

Other key points include:

Laura Hymas interview and the recording of her discussion with her oncologist (approximately 0:28 h in)

This section is horrifying (to Gorski, at least) to watch, as he can’t help but feel how dicey and ethical the situation that poor UK NHS oncologist found himself in with Hymas and her family demanding that he help her be part of one of Burzynski’s “clinical trials” by agreeing to be the local physician and agreeing to order various scans

The end of the story of Amelia Saunders (approximately 0:58 h in)

This is one where Merola caused Gorski true revulsion, as he basically implied that Amelia died because her parents took her off the antineoplastons

Or you can read what Eric Merola REALLY posted on Twitter:
https://stanislawrajmundburzynski.wordpress.com/2013/04/18/fact-checking-httpthehoustoncancerquack-com/
Hideaki Tsuda’s clinical trial (approximately 1:31 h in)

Gorski wonders why he hasn’t yet published, just like he wonders why Burzynski hasn’t published, but Gorski, SkeptiCoward© that he is, can NOT seem to explain why The Lancet Oncology Peer Review Team D-12-01519 refused to publish Burzynski’s 11/26/2012 (1:29:53) phase 2 clinical trial Progression-Free Survival (PFS) and Overall Survival (OS) re patients 8 – 16 years after diagnosis, results

Those of you who watch it, let Gorski know what you think

Those of you who can only watch part of it, let Gorski know what you think of that section

Remember, though, Gorski will BLOCK you if you question HIS infallibility, because he and his “Oracolytes” would rather comment on things that have NOTHING WHATSOEVER to do with Burzynski, like:

“it is possible to link without boosting google rankings through the “no-follow command”: http://en.wikipedia.org/wiki/Nofollow I learned about this from Bob Blaskiewicz, who proposed that we use this when linking to dubious websites in our posts”

Gorski makes unreliable excuses for NOT doing research re Burzynski, so I did it for him

Burzynski: Complete Response, Partial Response, Stable Disease, Progressive Disease, Objective Response, and Response:
https://stanislawrajmundburzynski.wordpress.com/2013/07/04/burzynski-complete-response-partial-response-stable-disease-progressive-disease-objective-response-and-response/
Burzynski: Progression-Free Survival (PFS):
https://stanislawrajmundburzynski.wordpress.com/2013/07/04/burzynski-progression-free-survival/
Antineoplastons: Adverse Effects:
https://stanislawrajmundburzynski.wordpress.com/2013/07/02/antineoplastons-adverse-effects/
Burzynski: Acknowledgements, Authors, and Co-Investigators:
https://stanislawrajmundburzynski.wordpress.com/2013/07/03/burzynski-acknowledgements/
Burzynski: Institutional Review Board (IRB):
https://stanislawrajmundburzynski.wordpress.com/2013/07/02/burzynski-institutional-review-board-irb/
And because Gorski and others do NOT seem to understand how antineoplastons (ANP) A10 (Atengenal) and AS2-1 (Astugenal) work, I provide the relevant Burzynski publications and page #’s for them to review:
http://www.burzynskiclinic.com/scientific-publications.html
======================================
Interim Reports on Clinial Trials
16. 2003 (BT-11)
Phase II study of antineoplaston A10 and AS2-1 in patients with recurrent diffuse intrinsic brain stem glioma: a preliminary report.
DRUGS IN R&D
http://www.ncbi.nlm.nih.gov/pubmed/12718563
Drugs in R and D
http://www.ncbi.nlm.nih.gov/m/pubmed/12718563
(Drugs in Research and Development)
http://www.burzynskiclinic.com/images/stories/Publications/960.pdf
Drugs R D. 2003;4(2):91-101
Drugs in R&D 2003;4:91-101

Pg. 92
Antineoplaston A10 and AS2-1 are synthetic derivatives of phenylacetate (PN) acid, glutamine and isoglutamine

A10 is sterile solution of sodium phenylacetylisoglutiminate (isoPG) in 4 : 1 ratio

Antineoplaston AS2-1 is sterile solution of sodium phenylacetate (PN) and phenylacetylglutaminate (PG) in 4 : 1 ratio

Pg. 97
Discussion
Pg. 99

======================================
Review Articles on Clinical Trials:
1. 3/2004
The Present State of Antineoplaston Research
http://www.burzynskiclinic.com/images/stories/Publications/994.pdf
Integrative Cancer Therapies 2004;3:47-58
Volume 3, No. 1, March 2004
DOI: 10.1177/1534735-403261964
Volume 3 Number 1 March 2004

Pg. 47
Pg. 48
Mechanism of Action of Antineoplaston
Pg. 49
Pg. 50

The reason for 50% Progressive Disease (PD) in studies is long dose-escalation process, which extends to more than a month’s time period, before the optimal dosage is reached

Pg. 56
Conclusion

======================================
Case Reports:
4. 9/2004 (Special Exception (SE) to BT-11 Study (ST))
Long-term survival and complete response of a patient with recurrent diffuse intrinsic brain stem glioblastoma multiforme
http://www.burzynskiclinic.com/images/stories/Publications/1145.pdf
Integrative Cancer Therapies 2004;3:257-261
Volume 3, Number 3 September 2004
DOI: 10.1177/1534735404267748

Pgs. 257-258
Pg. 260
Discussion
Pg. 261

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Interim Reports on Clinial Trials:
2. 10/2004
Phase II study of Antineoplastons A10 and AS2-1 (ANP) in recurrent glioblastoma multiforme
http://www.burzynskiclinic.com/images/stories/Publications/1218.pdf
Neuro-Oncology. 2004; 6: 384
Volume 6 Issue 4 October 2004
Abstracts from the Society for Neuro-Oncology Ninth Annual Meeting, Toronto, Ontario, Canada, November 18-21, 2004

Pg. 385
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Interim Reports on Clinial Trials:
3. 10/2004 (Study (ST) and Special Exception (SE))
Long-term survivals in phase II studies of Antineoplastons A10 and AS2-1 (ANP) in patients with diffuse intrinsic brain stem glioma
http://www.burzynskiclinic.com/images/stories/Publications/1219.pdf
Neuro-Oncology. 2004; 6: 386
Volume 6 Issue 4 October 2004

Antineoplastons (ANP) consist of 3 active ingredients including sodium salts of phenylacetylglutamine (PG), phenylacetylisoglutimine (isoPG), and phenylacetic acid (PN)

Preclinical data supports that the mechanism of antineoplastic activity in DBSG, involves interruption of signal transmission in the RAS, (PN) AKT2, and TGFB1 (PG) pathways, activation of p53 and p21 tumor suppressor genes (PN) and apoptosis (PG and isoPG)

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Interim Reports on Clinial Trials:
17. 2004 (BT-13 and BT-23)
Phase II study of antineoplaston A10 and AS2-1 in children with recurrent and progressive multicentric glioma :
a preliminary report
DRUGS IN R&D
http://www.ncbi.nlm.nih.gov/pubmed/15563234
Drugs in R and D
http://www.ncbi.nlm.nih.gov/m/pubmed/15563234
(Drugs in Research and Development)
http://www.burzynskiclinic.com/images/stories/Publications/1194.pdf
Drugs R D. 2004;5(6):315-26
Drugs R&D 2004;5(6):315-326.

Pg. 316
Pg. 324
Discussion

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Interim Reports on Clinial Trials:
18. 6/2005 (CAN-01 and BT-12)
Burzynski, S.R., Weaver, R.A., Janicki, T., Szymkowski, B., Jurida, G., Khan, M., Dolgopolov, V.
Long-term survival of high-risk pediatric patients with primitive neuroectodermal tumors treated with Antineoplastons A10 and AS2-1
http://www.ncbi.nlm.nih.gov/pubmed/15911929
Integr Cancer Ther. 2005 Jun;4(2):168-77
http://www.ncbi.nlm.nih.gov/m/pubmed/15911929
Integrative Cancer Therapies 2005;4(2):168-177
http://www.burzynskiclinic.com/images/stories/Publications/1220.pdf
DOI: 10.1177/1534735405276835
http://m.ict.sagepub.com/content/4/2/168.long?view=long&pmid=15911929
Volume 4 Number 2 June 2005

Pg. 168
Pg. 174
Discussion
Pgs. 175-176

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Interim Reports on Clinial Trials:
19. 3/2006 (BT-03, BT-11, BT-18, and CAN-01)
Targeted therapy with Antineoplastons A10 and AS2-1 of high grade, recurrent, and progressive brainstem glioma.
http://www.ncbi.nlm.nih.gov/pubmed/16484713
Integr Cancer Ther. 2006 Mar;5(1):40-7
http://www.ncbi.nlm.nih.gov/m/pubmed/16484713
Integrative Cancer Therapies 2006;5(1):40-47
http://www.burzynskiclinic.com/images/stories/Publications/5825.pdf
DOI: 10.1177/1534735405285380
http://m.ict.sagepub.com/content/5/1/40.long?view=long&pmid=16484713

Pgs. 40-41
Pg. 46
Discussion
Conclusion

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Interim Reports on Clinial Trials:
8. 10/2006
Treatment of multicentric brainstem gliomas with antineoplastons (ANP) A10 and AS2-1.
http://www.burzynskiclinic.com/images/stories/Publications/2105.pdf
Neuro-Oncology. 2006; 8:466.
Volume 8 Issue 4 October 2006
Abstracts for the Eleventh Annual Meeting of the Society for Neuro-Oncology (SNO)

Pg. 466
Antineoplastons (ANP) are synthetic analogues of naturally occurring phenylacetylglutamine (PG), phenylacetylisoglutimine (isoPG), and phenylacetate (PN)

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Review Articles on Clinical Trials:
3. 12/2007
Recent clinical trials in diffuse intrinsic brainstem glioma. Cancer Therapy 2007; 5, 379-390.
http://www.burzynskiclinic.com/images/stories/Publications/5692.pdf
Review Article
Cancer Therapy Vol 5, 379-390, 2007
http://www.cancer-therapy.org/CT/v5/B/HTML/42._Burzynski,_379-390.html
Volume 5 Number 2 December, 2007

Pg. 381
Pg. 384
E. Multitargeted therapy

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Interim Reports on Clinical Trials:
11. 10/2008
(BT-8 – PATIENTS WITH ANAPLASTIC ASTROCYTOMA)
(BT-15 – ADULT PATIENTS WITH ANAPLASTIC ASTROCYTOMA)
Phase II study of antineoplastons A10 and AS2-1 (ANP) in patients with newly diagnosed anaplastic astrocytoma:
A preliminary report
http://www.burzynskiclinic.com/images/stories/Publications/7853.pdf
Volume 10 Issue 5 October 2008
Neuro-Oncology 2008; 10:821
Abstracts for the Thirteenth Annual Meeting of the Society for Neuro-Oncology, November 20-23, 2008

Pg. 821

Antineoplastons (ANP) are synthetic analogs of naturally occurring phenylacetylglutamine (PG), phenylacetylisoglutimine (isoPG), and phenylacetate (PN)

Antineoplastons (ANP) is a multi-targeted therapy affecting signal transduction, the cell cycle, the TCA cycle, and apoptosis

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Interim Reports on Clinical Trials:
12. 12/2008
(BT-8 – PATIENTS WITH ANAPLASTIC ASTROCYTOMA)
(BT-15 – ADULT PATIENTS WITH ANAPLASTIC ASTROCYTOMA)
Phase II study of antineoplastons A10 and AS2-1 infusions (ANP) in patients with recurrent anaplastic astrocytoma
http://www.burzynskiclinic.com/images/stories/Publications/7898.pdf
Neuro-Oncology 2008; 10:1067
Volume 10 Issue 6 December 2008
Abstracts for the Eighth Congress of the European Association for Neuro-Oncology (EANO), Sept. 12-14, 2008, Barcelona, Spain

Antineoplastons (ANP) affects multiple targets, and its components have different mechanisms of action

A10 interferes with signaling in the AKT2 and MYCC pathways, blocks expression of TGFB1, activates the PTEN and MAD tumor suppressor genes, and normalizes nuclear transport by decreasing the expression of RANBP1, which may restore the activity of the mutated INI protein

AS2-1 interferes with signal transmission in the RAS and BCL2 pathways and activates expression of the tumor suppressors TP53 and p21

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Case Reports:
1. 12/2009 (BT-11 Special Exception (SE))
Over a 10-year survival and complete response of a patient with diffuse intrinsic brainstem glioma (DBSG) treated with antineoplastons (ANP).
http://www.burzynskiclinic.com/images/stories/Publications/8638.pdf
Neuro-Oncology 2009; 11:923.
Volume 11 Issue 6 December 2009
Abstracts from the Third Quadrennial Meeting of the World Federation of Neuro-Oncology (WFNO) and the Sixth Meeting of the Asian Society for Neuro-Oncology (ASNO), May 11-14, 2009, Yokohama, Japan

Antineoplastons (ANP) is a multi-targeted therapy that is well tolerated with minimal and reversible adverse events and has multiple different mechanisms of action by affecting the AKT, RAS, TP53, p21, and PTEN pathways
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