By Keir Liddle
Yesterday I posted a Skeptical overview of the latest email from Burzynski:the Movie creator Eric Merola and looked one by one at the claims contained within. As you may recall I said one claim was worthy of further comment and analysis: the nature and value of the Japanese research from Kurume University into antineplasteons.
Now I have had time to read and digest the available published literature I can give you my analysis.
In total I discovered eight studies (a ninth still eludes me) by Tsuda looking at the antineoplastons AS2-1 and A10 (the most popular of all the antineoplastons Burzynski claims to have discovered) of these four mention research on patients. One is a single case study, two are based on a single small study into human hepatocellular carcinoma (HCC) (found here and here) with the latter of these only making reference to one patient and the final publication is a phase one trial of ANP with 42 enrolled patients.
The rest of the research relates to animal research and cell line work. These types of study have limited applicability in determining whether or not a treatment will be efficacious in humans. They are an essential step in the research process and by no means should they be dismissed out of hand but unless they are coupled with large positive results in phase two and three clinical trials their value is limited.
I’m sure I don’t have to tell you of the limits of a single case study in determining the efficacy of a treatment so that paper is largely irrelevant in the grand scheme of things though don’t doubt that it will likely come up time and again cited as evidence that ANP work. For similar reasons I am excluding this paper that only references human studies in passing on one patient.
This leaves is with the two available published studies into ANP from the University of Kurume to cast a critical gaze over. Unlike Burzynski, whose dubious research practices have been well documented, there is currently no reason to assume Dr Hideaki Tsuda is anything other than an upstanding medical researcher. So I am doing my best to assess these studies uninfluenced by any bias from their association with Burzynski. I have been sent links regarding Tsuda and Burzynski but I will not be reading these until I have written the following analysis.
This paper ”Toxicological Study on Antineoplastons A-10 and AS2-1 in Cancer Patients” was received for publication in 1995 and published in the University of Kurumes own medical journal. The first important point about this study is that it cannot be used to evaluate the efficacy of ANPs as they were used in conjunction and combination with other chemotherapy agents and radiotherapy. Antineoplaston A-10 oral formulation and A-10 injectable formulation was administered in 14 and 25 patients respectively. The maximum daily dose was 10 g and 40 g, respectively and the longest term of administration was 610 days and 67 days, respectively to 33 and 10 patients respectively.
The study reports that all toxicological effects can be attributed to the conventional therapies provided and not the ANPs AS2-1 and A-10. Though this could be down to the low doses used in the study, presumably for safety, we know from patient blogs and the collapse of the NIH/Mayo clinic trial that Burzynski prefers high doses. The study reports:
“disappearance or measureable shrinkage of the tumor lasting more than one months as visualized by magnetic resonance imaging or computed tomography was seen in 15 tumors (32.6%). No increase in size of tumor for more than 3 months was observed in 8 (17.4%). The mean survival time of these patients was significantly longer than that in patients with tumors showing progressive increasing (17.52+3.31 months vs 4.80+0.65 months, p<0.005)”
This may seem a favourable result for Burzynski but we must remember that traditional therapy was provided alongside ANP, there was no randomisation involved and the sample size was small. In short this paper cannot be used to support the notion that antineoplastons work in isolation from conventional therapies and can only be used to indicate the weakest of evidence for ANPs working alongside conventional therapies.
The second paper is in effect a best case series featuring nine patients who were treated with ANP. Six of the patients under went radiochemotherapy (Table 1) and surgical resection of the tumors so it is impossible to attribute any recovery in these patients solely to the use of ANP additionally all patients with gliomas were treated with remission maintenance therapy. A complete response (defined as complete disappearance of the tumour) occurred in only one of the cases detailed, partial responses were found in two further cases (more than 50% reduction in tumour size), no change (between less than 25% increase or decrease in tumour size) was found in a further two cases and disease progression was found in the remaining four (more than 50% growth). Adverse effects of Antineoplaston were itchy skin rash, stiff finger joints, excess abdominal gases and mild myelosuppression (a decrease in cells responsible for providing immunity, carrying oxygen, and those responsible for normal blood clotting).
This study concludes their may be some usefulness of antineoplaston in the maintenance therapy of malignant brain tumours but is not confident on it’s use as a treatment in it’s own right. Interestingly similar results have been found for sodium phenylbutrate that suggest it could be used as a potential differentiation-inducing agent in malignant glioma and acute myeloid leukaemia. A differentiation inducing agent assists in the breaking down of cancer cells but does not trigger it or cause it.
Another published paper, which I have been unable to obtain a full text copy of, reports the results of a small 10 patient phase two trial. The abstract reveals that the ANPs used (AS2-1 and A10) do not operate as a treatment for cancer but they do delay recurrence of cancer. Though for completeness it would be nice to see a full text version of the paper and judge it on more than the abstract.
In short, unless supporters of Burzynski can provide more evidence, it seems the quote from Hideaki Tsuda in the latest Burzynski: the Movie email somewhat over eggs the pudding.
“After twenty-seven years of independently testing Antineoplastons—including randomized clinical trials, we found that Dr. Burzynski was right. It’s obviously not anecdotal any more.”
Unless Tsuda has reported these results in papers are not indexed by any of the major medical indexing services or that are published in journals more obscure than his home Universities publication I find it hard to see how he can back this up