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Things I Think About, by Peter Bowditch

Burzynski’s “research” – Part 1

Cancer quack Stanislaw Burzynski has 61 clinical trials listed on the register at http://clinicaltrials.gov/ct2/results?term=burzynski. Here is an analysis of the progress so far:

Withdrawn 7
Terminated 2
Completed 1
Unknown status 50
Not yet started 1

His supporters love to point to evidence of his success and can become quite abusive when anybody questions them. One piece of evidence they continually offer is the fact that he has a Phase 3 trial listed, but unfortunately that’s not really evidence of anything as it’s the trial that hasn’t even started recruiting subjects yet. My guess is that Burzynski has no intention of ever starting that trial and it is just there for advertising purposes. No results have been published for the single completed trial, although it was supposedly finished in 2006.

Over the last two weeks his supporters have been calling all his detractors liars for saying that he doesn’t publish anything and therefore there is no evidence of him curing anybody of anything. Oh yes, there are countless anecdotes and many web sites begging for money to send terminally ill children to Texas for a miracle cure. As Burzynski has been using web sites begging for money to save sick kids as an advertising gimmick for years not a lot has changed. What we want to see are papers in reputable peer-reviewed journals reporting on the results of double-blind randomised trials. You know, the sort of stuff we expect everyone else to do.

Why we are liars is because he has actually published something and I have been given links to it on at least a dozen occasions so I assume it’s the best they’ve got. (One surprising thing is that some of his supporters seem to think that PubMed is a medical journal. It’s an index to publications, so saying “He’s been published in PubMed” is like saying “He must be legitimate. He’s in the phone book”.) Here it is.

Integr Cancer Ther. 2006 Mar;5(1):40-7.

Targeted therapy with antineoplastons A10 and AS2-1 of high-grade, recurrent, and progressive brainstem glioma.

Burzynski SR, Janicki TJ, Weaver RA, Burzynski B.

Source

Department of Internal Medicine, Burzynski Clinic, Houston, Texas 77055, USA. srb@burzynskiclinic.com

Abstract

BACKGROUND: Brainstem glioma carries the worst prognosis of all malignancies of the brain. Most patients with brainstem glioma fail standard radiation therapy and chemotherapy and do not survive longer than 2 years. Treatment is even more challenging when an inoperable tumor is of high-grade pathology (HBSG). The objective of this report is to summarize the outcome of patients with HBSG treated with antineoplastons in 4 phase 2 trials. Patients: The following group of 18 patients was evaluable: 4 patients with glioblastomas and 14 patients with anaplastic HBSG. Fourteen patients had diffuse intrinsic tumors. Twelve patients suffered from recurrence, and 6 patients did not have radiation therapy or chemotherapy.

METHODS: Antineoplastons, which consist of antineoplaston A10 (A10I) and AS2-1 injections, were given in escalating doses by intravenous injections. The median duration of antineoplaston administration was 5 months, and the average dosage of A10I was 9.22 g/kg/d and of AS2-1 was 0.31 g/kg/d. Responses were assessed by gadolinium-enhanced magnetic resonance imaging and positron emission tomography.

RESULTS: The overall survival at 2 and 5 years was 39% and 22%, respectively, and maximum survival was more than 17 years for a patient with anaplastic astrocytoma and more than 5 years for a patient with glioblastoma. Progression-free survival at 6 months was 39%. Complete response was achieved in 11%, partial response in 11%, stable disease in 39%, and progressive disease in 39% of patients. Antineoplastons were tolerated very well with 1 case of grade 4 toxicity (reversible anemia).

CONCLUSION: Antineoplastons contributed to more than a 5-year survival in recurrent diffuse intrinsic glioblastomas and anaplastic astrocytomas of the brainstem in a small group of patients.

So let’s summarise that.

  • Publication in high-impact journals is always better. The journal Integrative Cancer Therapies can be expected to be sympathetic to outlandish alternative medicine claims. In 2011 it had an Impact Factor of 2.136 and was cited 687 times. By contrast, the Journal of Clinical Oncology had an Impact Factor of 18.970 and gets cited about 114,000 times each year. (Nature has an IF of 36.280. That’s where the Nobel Prize stuff gets published.)
  • It is not normal practice to divide the abstract up into the sections that are found in the main paper. I was taught that in my first year at university.
  • The paper was published in 2006, which is a long time ago in “cutting edge” medicine.
  • This is not a paper giving the results of a double-blind, randomised clinical trial.
  • It includes subjects from four trials, although which trials they are is not stated. It is not normal practice to aggregate trial data unless explicitly doing a meta-analysis and if that was the case the presentation of results would be completely different to what is given here.
  • There were only 18 patients in total across all four trials. I remember having sample size beaten into my head in my first year studying statistics and research methods.
  • “Fourteen patients had diffuse intrinsic tumors”. What did the other four have?
  • “Twelve patients suffered from recurrence” so only six improved (and Burzynski counts not getting worse as an improvement).
  • “6 patients did not have radiation therapy or chemotherapy” so twelve did, simultaneously with Burzynski’s treatment. (Many patients have to have had this sort of treatment before. Burzynski only accepts patients when all other options seem closed off. Desperate people are more ready to hand over money.)
  • There is nothing to say if the twelve patients who didn’t get better were the ones having radiation or chemotherapy, but if they were then the maximum number of patients who could have “improved” with Burzynski’s treatment alone is six. I suspect it was fewer.

More numbers:

All 18 subjects
Result % Subjects
Complete response 11% 2
Partial response 11% 2
Stable disease 39% 7
Progressive disease 39% 7

But wait –

All 18 subjects
Result % Subjects
5-year survival 22% 4
2-year survival 39% 7
Progression-free 6 months 39% 7

By remarkable coincidence, those numbers add up to 100%, despite the fact that the rows are not independent (each figure includes the one on the row below it). Also, as everyone in the 2-year survival group must have made it beyond six months this seems to indicate that nobody ever gets worse after six months. This seems highly unlikely. The numbers are also inconsistent with the numbers in the first table – surely “Complete response” should not be only half of “5-year survival”.

If this is the best research that Burzynski can come up with then I would hate to see the worst. In summary, a cobbled-together paper published in a low-impact journal six years ago which aggregates the results of four non-blinded trials with a small total number of subjects and which includes suspicious statistics is not about to get anyone the trip to Sweden that a cure for cancer would guarantee. If I had to rewrite the conclusion section of the paper it would say something like this:

CONCLUSION: We tried to find evidence that the treatments we have been selling at very high price for many years actually have an effect on the progression of certain forms of cancer. None of the clinical trials (that we pretend to do to get around the FDA’s ruling about unproven treatments) were good enough on their own to show efficacy so we cherry-picked some of them, put them together as if they were independent studies suitable for meta-analysis and then added some numbers to make things look good. We reported the numbers in two inconsistent ways, hoping that nobody would notice that we didn’t actually find any evidence of a cure. We even included an outlier to make the numbers look better, but we know that most people citing this paper will not know what that means or why it might be a problem.

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