I know I have readers who are neuroscientists. However, do I have readers who are currently attending the 4th Quadrennial Meeting of the Society of Neuro-Oncology in San Francisco going on this weekend? Why do I ask? Given the Regular readers might suspect that it has to do something with a man who has become a regular topic of this blog over the last two years. Yes, I’m referring to Stanislaw Burzynski, the oncologist who has never done a residency in internal medicine or a fellowship in oncology who was the subject of an excellent news report by Liz Szabo in USA TODAY one week ago today, the responses to which have ranged from the pathetic to the despicable, such as Eric Merola’s suggestion on Twitter (rapidly deleted but saved, thanks to Twitter notifications) that a certain critic of Burzynski whom we all know and (hopefully) love “find a gun & place in mouth.” Then, for pure, unbridled stupidity, it’s hard to beat Suzanne Somers, whose book Knockout devoted a whole chapter to praising Burzynski, who leapt into the fray to defend Burzynski a few days ago.
It’s probably a coincidence, given that these meetings were scheduled a long time ago, but since last Friday, the spin has been coming fast and furious out of the Burzynski Clinic. For example, on the very day that Szabo’s report was published, Burzynski issued a press release entitled Burzynski Clinic Presents Over Five Years Survival Data From Phase II Trials of ANP for Inoperable Brain Tumors at the Congress. Then, today at the poster presentation session at the Society of Neuro-Oncology meeting in San Francisco tonight between 7 and 9 PM he’s presenting two abstracts:
- NO-020 A Phase II study of antineoplastons A10 and AS2-1 in adult patients with recurrent glioblastoma multiforme based on Protocol BT-21. Gregory Burzynski*1,2, Stanislaw Burzynski1,2, Tomek Janicki1,2, Ania Marszalek1. 1Burzynski Clinic, USA, 2Burzynski Research Institute, USA.
- NO-021 A Phase II study of antineoplastons A10 and AS2-1 in pediatric recurrent diffuse intrinsic pontine glioma. Stanislaw Burzynski*1,2, Tomasz Janicki1,2, Gregory Burzynski1,2, Ania Marszalek1. 1Burzynski Clinic, USA, 2Burzynski Research Institute, USA.
OK, I don’t know whether Stan the Man himself will be standing in front of his poster for two hours, but presumably one of the authors will. In any case, now you know why I’m wondering if any of you are at the Neuro-Oncology meeting right now. Basically, I’d love to see what’s on those posters, as the abstracts (as most conference abstracts are) isn’t particularly helpful. No, I don’t want anyone to harass whoever’s standing in front of the poster, although if it is Burzynski himself real neurosurgeons, neuro-oncologists, and neuroscientists studying brain cancers are encouraged to grill him (politely and only about the science!) about his results and report back. If he’s passing out copies of his poster, as is often done at these conferences, please get a copy, scan it, and e-mail it to me. Sadly, I know it’ll be midnight here when the poster session in San Francisco is over, but that’s OK.
Because there isn’t (yet) a press release from the Burzynski Clinic about his results, let me just jump back to the first press release from the conference in China:
The Burzynski Clinic (BC) announced today that it made a keynote speaker presentation at the 2nd Annual Congress of Asia-Pacific Academy of Anti-Aging Medicine in Beijing, China. Based on the presentation in Beijing, a total of 401 eligible patients (patients who received over 28 days of treatment) with advanced inoperable brain tumors have been treated with antineoplaston A10 and antineoplastons AS2-1 therapy (ANP) in phase II studies. Most of the patients (87%) were diagnosed with high-grade tumors and the remaining patients were diagnosed with low-grade tumors. The patients were diagnosed by pathologists not associated with BC and objective responses were verified by Central Radiology Review. The group of 77 patients (19%) survived over five years from the treatment start. Of particular interest were results in patients with brainstem gliomas. The group of 17 patients with brainstem glioma underwent the treatment and 65% of these patients survived over five years. An additional group of 42 patients diagnosed with diffuse intrinsic pontine glioma (DIPG) have been treated and a total of 19% survived over five years.
The quality of survival is very good and there is no long-term toxicity related to ANP.
These clinical results are very encouraging, since they describe a positive ANP effect on some of the worst malignancies in the entire oncology field, but they will require FDA approval.
There are a lot of red flags here, of course, the first of which is that the conference is the Asia-Pacific Academy of Anti-Aging Medicine. Anti-aging medicine tends to be, more than anything else, a cesspit of pseudoscience and quackery; so Burzynski fits right in. But what about the report itself. Obviously, it’s pretty much impossible to tell much from a self-serving press release, but there is one enormous additional red flag. Notice how the press release says that this is a report on a “total of 401 eligible patients (patients who received over 28 days of treatment) with advanced inoperable brain tumors have been treated with antineoplaston A10 and antineoplastons AS2-1 therapy (ANP) in phase II studies.” Actually, there are two red flags right in that passage. First, notice how it says only patients who received over 28 days of treatment were counted. This, by its very nature, selects for patients who are in good enough shape to tolerate 28 days of antineoplaston therapy, which, as we have seen, is highly toxic, Burzynski’s claims otherwise notwithstanding. Normally, the way good clinical trials are done involves an “intent to treat” analysis, in which every patient randomized is counted, including patients who could not tolerate the therapy and had to stop. That way, this selection bias is minimized. Think of it this way. If a patient has to stop therapy due to lack of tolerance or clinical deterioration, that counts as a patient for whom the treatment didn’t work. Now, this can be acceptable if the number of patients who didn’t receive over 28 days of treatment were stated, but it didn’t. That number is mandatory in any such report.
The second big red flag is the design of this study. This is not a single phase II study. Basically, from the report, it appears to be nothing more than Burzynski conglomerating all or some of his phase II studies into one big undifferentiated glob of patients and then reporting on them. Sorry, Stan, but it doesn’t work that way. You have to report each phase II study individually. Grouping them all together like this, particularly when we don’t know how he picked which studies he was going to group together, is complete nonsense. It’s meaningless drivel. Add to this the fast and loose way that Burzynski plays with patient records and has been found by the FDA to destroy original patient records, and there’s no reason to believe the validity of any of his report from China, and I don’t feel like spending any more time, except to note that Burzynski states that there are no “chronic toxicities.” Of course, we all know from Szabo’s report that there are a lot of acute toxicities from antineoplastons, including hypernatremia (sodium levels too high).
Moving on to the two posters, let me just say one thing that needs to be understood by the non-scientists who read this blog. Poster presentations are the lowest form of published scientific discourse. They get you an abstract, some exposure at the meeting if people are interested in your poster, and that’s about it. They’re also subject to the weakest peer review. For some meetings, pretty much every abstract is accepted. The good ones or the ones covering the hottest topics are accepted for oral presentations, such as plenary session talks (the best!) or talks in various parallel sessions (good but not as good as the plenary session). All the rest are relegated to poster presentations, and that’s where Burzynski is.
Now let’s look at Burzynski’s abstracts, which I’ll basically treat as the same thing, because, well, let’s face it, they are the same thing. The first one is NO-020:
Treatment of recurrent glioblastoma multiforme (GBM) creates one of the most difficult challanges in neuro-oncology. The aim of this presentation is to evaluate the responses and survival of 24 recurrent GBM patients and toxicity in all 33 eligible patients. The study accrued patients who developed disease progression during standard treatment within eight weeks from completion of radiation therapy (RT) and six weeks from chemotherapy. Forty candidates were registered but only 33 patients were eligible. The seven noneligible patients received less than 28 days of treatment with Antineoplastons A10 and AS2-1. Among the eligible patients there were 24 cases of recurrent GBM that progressed during prior treatment, four patients with anaplastic astrocytoma and five persistent GBM. Previous treatment included surgery in all patients (18 had tumor resection, and 6 underwent biopsy only), chemotherapy in 75% of patients and radiation therapy in 88% of patients. Antineoplastons were administered intravenously every four hours (median dose of A10 10.7 g/kg/d and AS2-1 0.43 g/kg/d) until objective response was documented or until progression. The median duration of ANP treatment was 13.2 weeks ranging (4.6 – 80.3). Responses were assessed by MRI repeated every eight weeks, and or PET scan. Objective responses were determined in 16.7% of cases (complete response, and partial response in 8.3% each). Progression-free survival at six months was 25%. Overall survival is 39.3% at one year, 4.4% at two years, five and ten years. The treatment was well tolerated with reversible grades 3 and 4 toxicity including four cases of hypernatremia, two of fatigue, two of hypokalemia, and a single case of somnolence. There were no chronic toxicities. In conclusion, ANP is well tolerated and compares favorably to the current treatment for recurrent GBM.
And the next one is NO-021:
Brainstem gliomas (BSG) are rare tumors of which diffuse intrinsic pontine gliomas (DIPG) comprise a distinct group. Numerous trials have been conducted in DIPG without a proven pharmacological treatment benefit. Prior interim report on this phase II study of antineoplastons (ANP) A10 and AS2-1 provided data on 40 patients diagnosed with BSG. This report is focused on final results of 17 out of 40 patients diagnosed with recurrent pediatric DIPG (RPDIPG). The median age in this group was 8.8 years (range 4.5-18.5), with 9 females and 8 males. Previous treatment included radiation therapy (RT) in 15 patients, chemotherapy in 11 patients and surgery in 2 patients. At least eight weeks elapsed from initiation of ANP and previous RT and six weeks from chemotherapy with nitrosoureas. ANP was administered daily through a subclavian venous catheter via infusion pump. The median duration of treatment was 5.6 months. The median of average dosages of A10 was 8.8 g/kg/d and 0.40 g/kg/d of AS2-1. Responses were assessed by MRI repeated every eight weeks. In the RPDIPG group, a complete response (CR) was 6%, partial response (PR) 23.5%, and stable disease (SD) 23.5%. 6 month progression-free survival (PFS) was 35.3%. 1 year overall survival (OS) was 29.4%, 2 years 11.8%, and 5, 10 and 14 years 5.9%. One patient has OS and PFS of 14 years from the treatment start. Grade 4 toxicities including hypernatremia, hypokalemia and fatigue occurred in less than 18% of patients. Grade 3 fatigue, somnolence, skin allergy and urinary incontinence occurred in 6-12 %. There were no chronic adverse events. Responding patients experienced improved quality of life. The results suggest that ANP shows efficacy and an acceptable tolerability in patients with RPDIPG.
Once again, it’s very telling that in both abstracts, Burzynski reports there being no “chronic adverse events.” One notes that this very term is generally a bit dodgy and obviously designed to be able to avoid discussing acute adverse events, such as, again, hypernatremia. There are others, however, as I’ve discussed before, and they include high fevers (remember, Hannah Bradley documented fevers to 104° F in her video), rashes, and others. If a patient suffers life-threatening acute toxicities and no significant benefit in terms of improvement in long-term survival, then it’s likely to be a useless drug (and, make no mistake, antineoplastons are a fairly toxic drug, the claims of “natural healing” advocates notwithstanding).
Also, I can’t help but notice again that Burzynski is very canny about how he chooses which patients to present. In the first abstract, he presents only survival data from the 24 patients who completed 28 days of ANP therapy. The second abstract is even more questionable in that he references a previous preliminary report on 40 patients and then focuses this report on the final results of 17 of these patients, less than half! Why? This is a glaring omission. What happened to the other 33 patients, and why aren’t their “final” results reported? If this is the sort of work that Burzynski has been submitting to journals like The Lancet Oncology, it’s no wonder why he’s been having trouble getting published. Then he blithely mentions that grade 4 toxicities were observed in “less than” 18% of patients. Remember, grade 4 toxicities are, by definition, life-threatening toxicities that require urgent intervention. The only grade higher is grade 5, which is death itself! The next time some clueless Burzynski shill tries to claim that ANPs are “non-toxic,” I will point them to Burzynski’s own most recent abstract above, which shows that nearly one in five patients receiving ANPs suffered life-threatening toxicities. Grade 3 toxicities are, by definition, “severe but not life-threatening; hospitalization required; limitation of patient’s ability to care for him/herself,” and Burzynski reports “6 to 12%” of patients had grade 3 toxicities. Which was it? In any case, by Burzynski’s own abstract, up to 30% of patients suffer severe to life-threatening complications from ANP therapy.
As for the survival rates, neither abstract is that impressive, particularly given that an intent-to-treat analysis was clearly not done and the patients analyzed appear to have been almost cherry-picked. For instance, when M.D. Anderson reports its survival rates for recurrent DIPG, it doesn’t exclude half its patients. Moreover, we know that M.D. Anderson knows how to assess tumor response. Burzynski, on the other hand, does not, and he doesn’t even bother to keep the original images of the MRI scans, to allow verification of responses by radiologists who actually know what they’re doing.
Then, in the first abstract, there’s this statement:
The study accrued patients who developed disease progression during standard treatment within eight weeks from completion of radiation therapy (RT) and six weeks from chemotherapy.
Remember what I said about pseudoprogression? Remember how late effects of treatment can mimic tumor progression, as Liz Szabo described in her report and I discussed on at least two occasions? Remember how someone who doesn’t realize that or accept it can be fooled into thinking a tumor is progressing and then, if therapy is started during pseudoprogression, fooled into thinking whatever therapy he started to administer during pseudoprogression was responsible for shrinkage of the tumor when in fact the tumor was just doing what tumors undergoing pseudoprogression do, their area of inflammation and necrosis shrinking down after the acute insult to the tumor tissue due to the therapy. Pseudoprogression is particularly common after radiation therapy but can happen as well after chemotherapy. Burzynski couldn’t have described a study more likely to be confounded by pseudoprogression if he had tried.
It’s really depressing to think that, even now, Burzynski can slither his way into a legitimate scientific conference because at the time of the submission of abstracts few people knew how bad his science and medicine are, and even fewer knew his propensity for misreading and misassigning responses, miscategorizing and not reporting adverse events, and destroying patient records. Hopefully, Liz Szabo’s USA TODAY report took care of that problem.
In the meantime, if you’re at the Neuro-Oncology Conference, don’t forget to drop by Stan’s posters and tell him (or whoever’s manning them) that Orac said hi.