If you remember, the last time I wrote about Burzynski, the Food and Drug Administration (FDA) had caved, and by “caved” I mean that it had lifted the partial clinical hold on Burzynski’s clinical trials. As is usual with the long and winding saga that is Burzynski, I feel compelled to give a brief review for any newbie who might encounter this post. Old hands at this story can skip ahead or just skim.
Two years ago, a child named Josia Cotto died of hypernatremia (elevated sodium level in the blood) due to receiving treatment for a brain tumor from the Burzynski Clinic using Burzynski’s “miracle drug” antineoplastons. Hypernatremia is a known complication of ANP treatment, and, as a result of this child’s death, the FDA put a partial clinical hold on Burzynski’s clinical trials for pediatric patients, which meant that he could continue to treat children already enrolled in his clinical trials but could not enroll any new patients. Six months later, this partial hold was extended to all of Burzynski’s clinical trials, and in early 2013 the FDA inspected the Burzynski Clinic and Burzynski Research Institute (BRI).
The reason why the FDA’s decision late last month to lift this clinical hold is so puzzling is because the results of the FDA’s inspection were so damning. In particular, the FDA found that Burzynski exaggerated responses to therapy using inappropriate criteria, didn’t have original scans of many patients, and played fast and loose with the rules regarding enrolling patients onto clinical trials under single patient INDs (otherwise known as compassionate use exemptions). Let’s just say that Burzynski’s institutional review board (IRB), the committee whose charge under the Common Rule (which clinical trials meant to be used as the basis for FDA approval of a drug must follow) wasn’t exactly rigorous about following federal regulations or protecting patient rights and safety, and let’s further say that Burzynski’s response was…less than convincing. More puzzling, this is not the first time that the FDA has investigated Burzynski and found the very same sorts of violations by the BRI IRB; it’s a pattern that goes back to at least 2001 and continued at least until the FDA inspection. Let’s just put it this way. IRBs are supposed to be as independent as possible, and Burzynski’s IRB has been (and still is) chaired by Carlton F. Hazlewood, PhD, who just so happens to be on the board of directors of the Burzynski Research Institute. The conflict of interest and lack of ethics are astounding. Yet the FDA still lifted the partial clinical hold, a breathtaking failure to protect cancer patients.
That was the bad news.
The Texas Medical Board tries to do the right thing
During this time, the Texas Medical Board, which has tried and failed to strip Burzynski of his medical license on multiple occasions over the last four decades, has decided to take another whack at the piñata. I’m glad it did, even though, as has been discussed before with respect to multiple cases, including Rolando Arafiles and Christopher Duntsch, the TMB is toothless by design, thanks to an anti-regulatory bias that has led to laws that have vastly weakened its already-weak regulatory authority. That’s why, although I’m not optimistic that this time the TMB will prevail where in the past it has not, I’m glad it’s giving it the old college try, which is what it has done with an amended complaint against Burzynski dated July 10, 2014. I warn you: It’s over 200 pages long, but the spacing and repetition are such that I was able to read most of it even though I was busy with TAM. It’s a devastating document that, if the allegations are proven in court, should finally end Burzynski’s career. I’ll apologize if I’m a bit pessimistic, though. Burzynski has slithered out of tighter spots before.
Still, it’s worth discussing the allegations. Because of the length of the document, I can only hit the high points, but the complaint is there for you all to read if you are so inclined. If you’ve been following the Burzynski saga it’s definitely worth taking the time to do so. The introduction sets the stage:
Board Staff alleges that Respondent created a medical practice model based on marketing his proprietary anti-cancer drugs to patients without adequate measures for patient safety and therapeutic value. Respondent misled patients knowingly by promoting these drugs as an attraction to bring patients to his medical practice when Respondent was aware that he could not legally include most of those patients in FDA-approved Phase 21 clinical trials of his proprietary anti-cancer drugs. Respondent further misled patients into paying funds as a retainer prior to receiving any evaluation, diagnosis or treatment. Respondent further misled patients into: (1) paying exorbitant charges for drugs and medical services; (2) accepting care from unlicensed persons while Respondent and Respondent’s employees misrepresented those unlicensed persons to be licensed medical doctors in Texas and the United States of America; and (3) accepting care from health care providers who had little advanced education or training related to cancer treatment while Respondent and Respondent’s employees misrepresented those health care providers to be doctors with significant advanced education or training related to cancer treatment.
Having followed the Burzynski saga for three years now, I’m always heartened to see when a regulatory or law enforcement body “gets it” the way this paragraph demonstrates that the TMB appears to “get it” now. This is in sharp contrast to the weaselly justifications by the FDA for unleashing Burzynski’s bogus clinical trials—which, recall, his own lawyer characterized as “an artifice, a vehicle we and the FDA created to legally give the patients Burzynski’s treatment” so that Burzynski “would be able to treat almost any patient he would want to treat!”—on unsuspecting desperate cancer patients again. The new allegation that I hadn’t been aware of was the part about using health care providers with little or no education or skill and representing them to patients as being doctors. Now that’s really bad by any stretch of the imagination, and a profound betrayal of the cancer patients whose desperation led them to Burzynski.
Several of those desperate cancer patients are described in the complaint. I’m not going to go through all the cases, because there’s a depressing similarity to them in terms of the allegations of Burzynski’s wrongdoing, but it’s worth discussing at least a couple of them. I’ll start with Patient A, not only because it’s the first patient listed but because it’s a different story than we normally see at the Burzynski clinic. This patient had suspected colon cancer. I say “suspected,” because at the time he first presented to Burzynski he had not had any biopsies.
Patient A presented to the Burzynski clinic with a diagnosis of “sigmoid colon carcinoma metastatic to the liver.” This diagnosis was made on the basis of imaging studies that showed lesions in the liver suspicious for metastases and a colonoscopy that showed a “polypoid mass consistent with high-grade dysplasia and suspicious for invasive adenocarcinoma.” This, unfortunately, is not an uncommon presentation of colon cancer, except for one thing. Usually, there’s a biopsy done. A cardinal rule for treating cancer patients is that you do not initiate treatment without a tissue diagnosis from a biopsy. This tissue both proves that the patient has cancer and identifies the kind of cancer it is. Indeed, these days, when molecularly-targeted therapy is being increasingly used, the tissue also allows analysis of gene expression patterns that can guide the choice of treatment. The situations in which it is considered acceptable to begin treatment of presumed cancer in the absence of a tissue diagnosis are very uncommon and boil down to rare cases where the imaging is pathognomonic of the kind of cancer suspected and the clinician judges that a biopsy would be too risky.
Basically, patient A should have had a biopsy of both his sigmoid colon lesion and one or more of his liver lesions. There was no reason not to do this, as colonoscopic biopsies and needle biopsies of the liver are in general low risk procedures and the treatment of colon cancer is, increasingly, being guided by newer gene tests. Now, in fairness, Patient A had refused to undergo a biopsy when his local physician had recommended it and also refused to consider chemotherapy with FOLFOX3 with Avastin after a biopsy, which is within the standard of care. However, if that’s the case then Burzynski should have refused to treat him. Not only is it considered a gross breach of the standard of care not to have a tissue diagnosis before treating a patient, but nearly all clinical trials for cancer treatments absolutely require a tissue diagnosis, which means that this patient was ineligible for any of Burzynski’s clinical trials. Instead, without even recommending a biopsy, Burzynski began to treat patient A with anticancer medications.
Now here’s the kicker:
9. At the time Patient A first met with Respondent and the other employees of the Burzynski Clinic, Respondent allowed Tolib Rakhmanov, a person who is not a licensed physician or health care provider in Texas or elsewhere in the United States of America, to represent to Patient A that Tolib Rakhmanov was a licensed medical doctor practicing medicine in Texas. Respondent and the other Burzynski Clinic employees under Respondent’s supervision and control continued to represent to Patient A and Patient A’s fiancee or to allow them to believe that Tolib Rakhmanov was a licensed medical doctor practicing medicine in Texas throughout Patient A’s treatment at the Burzynski Clinic.
10. Respondent and the other Burzynski Clinic employees under Respondent’s supervision and control referred to Tolib Rakhmanov as “Dr. Rakhmanov” in Patient A’s and Patient A’s fiancée’s presence. Respondent knew or reasonably knew that Tolib Rakhmanov signed documents, many of which were also signed by Patient A and Patient A’s fiancee, in manners that identified Tolib Rakhmanov as a medical doctor. Patient A and Patient A’s fiancée reasonably believed that Tolib Rakhmanov was a medical doctor licensed to practice medicine in the state of Texas. Respondent was responsible for the false, misleading and deceptive representation to Patient A and Patient A’s fiancée that Tolib Rakhmanov was a medical doctor licensed to practice medicine in the state of Texas.
Rakhmanov also performed tasks and services that obviously constitute the practice of medicine, including diagnosing and evaluating Patient A’s medical condition, making treatment recommendations, on numerous occasions (with all the dates listed). The TMB further alleges that Burzynski “directed and/or reasonably knew and allowed Tolib Rakhmanov, a person who is not a licensed physician or health care provider in Texas or elsewhere in the United States of America, to perform medical tasks that constituted the practice of medicine in the state of Texas in the evaluation, diagnosis and treatment of Patient A.”
Burzynski also promised the patient that he would receive ANPs and the FOLFOX/Vectibix treatment he desired, after which he demanded a large retainer for treatment. This is interesting, because Vectibix (generic name: panitumumab) is a targeted therapy that is only useful in cancers with a gene called KRAS that is not mutated. (KRAS is gene that is frequently mutated in colorectal cancer.) This is what I mean about how gene testing is becoming more important in colorectal cancer. Most colorectal cancers these days are tested for KRAS mutations to determine if Vectibix is an appropriate therapeutic regimen. According to the company’s website, Vectibix is “not indicated for the treatment of patients with KRAS-mutant mCRC [metastatic colorectal cancer] or for whom KRAS mutation status is unknown.” In other words, it was unequivocally not indicated for Patient A. That’s even leaving aside the issue of ANPs.
Actually, Patient A never received FOLFOX/Vectibix or ANPs. Instead, he received something else from Burzynski without his “adequately explaining to Patient A the difference in safety and efficacy between the therapy requested by Patient A and the therapy provided by Respondent and the employees of the Burzynski Clinic under his supervision and control.” Instead, Burzynski initiated treatment with phenylbutyrate. Remember phenylbutyrate? It’s the orphan drug that Burzynski touts as an ANP prodrug. Patient A also received a “partially FOLFOX equivalent regimen” consisting of oral Xeloda and intravenous Avastin, which I consider kind of a half-assed treatment that isn’t FOLFOX. Apparently Patient A improved for a while, which is quite possible given that he was receiving Xeloda (capecitabine), for which there is some evidence of efficacy, as well as Avastin, which is why it’s sometimes used as an alternative to FOLFOX. It’s unlikely that the phenylbutyrate did anything. I do have to note, however, that there is a passage in which “shrinkage” of a brain tumor is mentioned, which makes me think the TMB made a mistake and mixed up part of Patient B’s story with that of Patient A.
For some reason, Burzynski started changing drugs without adequate rationale. Eventually, the tumors started growing again, and the patient left Burzynski’s care, having paid an enormous amount of money, including a $4,500 monthly case management fee and a charge of $360 for 500 mg of sodium phenylbutyrate. During the course of Patient A’s treatment, Burzynski also used very expensive drugs that are not indicated for colorectal cancer, such as Afinitor (everolimus), which inhibits a protein called mTOR and is primarily used for kidney cancer and breast cancer, and Votrient (pazopanib), a tyrosine kinase inhibitor that blocks tumor growth, inhibits angiogenesis, and is used for renal cell carcinoma and soft tissue sarcoma.
The story is all very familiar if you’ve been following Burzynski and very depressing. There’s more, just in the case of Patient A, including failure to assess the patient’s mental status when recommending treatments, failing to provide anything resembling adequate informed consent, and having an ownership interest in the pharmacy dispensing the drugs Burzynski used, among other violations, but let’s move on to Patient B.
Patient B is an interesting case, because part of it isn’t clear to me. In December 2010, Patient B had a diagnosis of brain cancer, which was successfully removed by craniotomy, which was followed by imaging studies that showed complete removal of the tumor. Post-operative chemotherapy and radiation therapy were recommended. Now here’s a part where it’s hard to understand what Burzynski did wrong if you don’t know a lot about him. The complaint alleges that Burzynski didn’t get a biopsy to confirm the existence of cancer before initiating anticancer treatment. Yet, conventional doctors had recommended postop chemotherapy and radiation, even though as far as they could tell the cancer had been completely removed. The difference is in intent. The chemotherapy and radiation therapy were being recommended as adjuvant treatments, in other words, treatments designed to decrease the risk that the tumor would recur, given that microscopic disease is almost always left behind. My guess (and it’s only a guess) is that Burzynski didn’t document that he was undertaking treatment for adjuvant purposes but rather made it sound in the medical record as though he were treating for therapeutic purposes for an existing cancer.
Later in the complaint it is alleged that “Respondent and/or employees under his direction and control failed to inform Patient B about the FDA-approved criteria for treatment with antineoplastons in one of Respondent’s sponsored clinical studies.” None of Burzynski’s trials that I can find are for the adjuvant treatment of brain cancer. They are, instead, for the treatment of existing brain tumors, most often recurrent or refractory brain tumors. Thus, Patient B almost certainly wasn’t eligible for any of Burzynski’s ANP clinical trials, because he had what we in the biz like to call “no evaluable disease,” often abbreviated NED, meaning that there wasn’t any currently detectable tumor whose response to therapy could be followed.
Next, we see the same depressing litany for Patient B as well, including lack of informed consent, failure to document treatment rationale, and, again, Burzynski Clinic staff who are not physicians being represented as such, including Tolib Rakhmanov and Larisa Tikhomirova. There again was the requirement for a large retainer to begin treatment. There was again the “bait and switch” in which Burzynski lured Patient B in with the promise of his ANP therapy and then used something different, including—of course!—phenylbutyrate, plus the usual witches’ brew of targeted drugs that we’ve seen before and that are not indicated in most brain cancers. It’s what I’ve referred to before as the “everything but the kitchen sink” approach.
In actuality, Patient B’s story in the complaint is poorly written and very confusing. I had trouble making heads or tails of part of it. It says that Patient B didn’t have any detectable tumor when he first consulted Burzynski in December 2010 and nails Burzynski for that, but then it describes Burzynski beginning treatment in February 2011 and an MRI scan:
On or about March 17, 2011, an MRI of Patient B’s brain revealed moderate decrease in the size of the brain lesion.
My guess, but I can’t be sure from the muddled and confusing description in the TMB complaint, is that this brain “lesion” was probably the inflammatory reaction to the patient’s surgery, which would have been expected to get smaller over the next three months anyway. A better way to say it would have been to be very clear from the start what the radiological findings were when the patient first approached Burzynski. If there was a lesion there, then it should have been pointed out whether it was suspicious for residual disease or whether the radiologists thought it was just normal postoperative changes. We can infer from the description that Patient B’s doctors must have thought that there was no residual disease, but then what is this “brain lesion” that was showing moderate decrease in size on March 17, 2011? I’m a cancer doctor who’s followed Burzynski, and even I’m not entirely sure what happened based on the description.
Be that as it may, many of the same complaints made against Burzynski for his treatment of Patient A apply to Patient B as well, and Patient B suffered considerable toxicity:
Respondent and other health care providers under Respondent’s direction and control treated Patient B without regard to the potential combined toxicities of drugs used pursuant to Respondent’s recommendations and directions. Respondent and other health care providers under Respondent’s direction and control referenced the case reports of other physicians not associated with the Burzynski Clinic as support for combined use of the drugs recommended and administered to Patient B. In those referenced case reports of physicians not associated with the Burzynski Clinic, however, those drugs were only used individually or in other combinations besides the combinations of drugs used for Patient B by Respondent and other health care providers under Respondent’s direction and control. In this regard, Respondent and other health care providers under Respondent’s direction and control violated the standard of care for reasons including:
a. Patient B suffered considerable toxicity affects.
b. Respondent violated the standard of care by failing to have an adequate medical rationale for this simultaneous use of these agents in anti-cancer therapy.
c. Respondent violated standards of adequate documentation by failing to document an adequate medical rationale for this simultaneous use of these agents in anti-cancer therapy.
d. Respondent also failed to adequately inform Patient B of this increased risk.
Same as it ever was. I note that Patient D’s case is a lot like Patient C’s case, one difference being that Sheryll Acelar was one of the non-physicians allegedly represented to the patient as a physician. Another name that came up as a Burzynski Clinic employees who was falsely represented to patients as being physicians was Lourdes DeLeon.
Patient G is different in that Patient G was actually enrolled on one of Burzynski’s phase II clinical trials for a malignant astrocytoma of the optic nerve. For this patient, not only were there many of the same violations as listed for Patients A through F, but there were added allegations based on Burzynski’s treatment of the patient as part of this clinical trial:
14. Respondent failed to comply with federal regulations, the Burzynski Research Institute’s agreement with the FDA regarding the clinical study program for administration of antineoplastons and the approved protocols for the approved clinical study in which Patient G was enrolled. Such failures included Respondent’s direction and allowance for Patient G to be charged for the antineoplaston therapy and Respondent’s direction and allowance for these charges to be characterized as something else, “chemo prolong infuse” . This characterization was false, misleading and deceptive.
40. The federal regulatory requirements for approval of single patient protocols for Phase 1 or Phase 2 clinical studies require that the investigator ensure that risks to patient/subjects are minimized and reasonable in relation to anticipated benefits.
41. Respondent, as principal investigator and as sponsor of the clinical study of antineoplaston therapy for Patient G, had a responsibility to ensure that risks to Patient G were minimized and reasonable in relation to anticipated benefits.
42. Ensuring that risks to patient/subjects are minimized and reasonable in relation to anticipated benefits requires (1) review of the subject’s medical records (history and physical examination) and (2) clarifying any outstanding issues with respect to the suitability of treating the patient/subject prior to granting institutional review board approval.
43. Respondent, as principal investigator and as sponsor of the clinical study of antineoplaston therapy for Patient G, failed to do the following to protect Patient G who was a patient/human subject in the clinical study of antineoplastons; (1) Respondent failed to take adequate measures to minimize risks to Patient G; and (2) Respondent failed to ensure that the risks to Patient G were reasonable in relation to anticipated benefits and the importance of the generalizable knowledge that may be expected to result.
44. Respondent’s failure, as principal investigator and as sponsor of the clinical study of antineoplaston therapy for Patient G, to ensure that risks to Patient G were minimized and reasonable in relation to anticipated benefits violated the standard of care, federal regulations, the Act and Board Rules.
This is the first time I’ve ever seen the TMB go after Burzynski for violating federal clinical trial regulations and human subjects research protections. I would like to see more of this. Another aspect of this case is unusual in that the TMB notes that the patient’s parent was allowed “to open an account whereby the public could read about Patient G’s medical and financial crisis and contribute money to that account.” The TMB alleges that Burzynski and his staff “reasonably were aware that the website that hosted this contribution account would provide any donations directly to the Burzynski Clinic to pay for the costs of Patient G’s treatment and that such costs had already been paid in advance by Patient G’s parent.” Patient G’s parent had a billing dispute with the Burzynski Clinic in which Burzynski refused to accept those donations as credit on Patient G’s account at the Burzynski Clinic and returned all the donations to the website that had acted as an intermediary for the donations. Burzynski also received significant reimbursement payments from an insurance company for Patient G’s care and refused to refund Patient G for benefits paid.
In other words, it’s all about making money from the dying and desperate.
And all the rest…
The TMB complaint also describes something that people who’ve been following the Burzynski case are well aware of, namely his advertising claims for ANPs, which are illegal under federal law because he made specific health claims for them and they are not yet FDA-approved for any indication. This is one thing that I haven’t been able to figure out. If a drug company did this, all the “natural health” advocates who defend Burzynski tooth and nail would howl bloody murder—and rightly so. But Burzynski does it, and he’s a hero being “persecuted” by the FDA and TMB. Ditto Burzynski’s failure to meet criteria for human subjects protection again and again, which are detailed very carefully in the last 30 pages or so of the complaint.
So what does it all mean? At the very least, it means that the TMB is serious this time. Does it mean that finally—finally—Burzynski is going down? I certainly hope so. Unfortunately, there’s no guarantee, and Burzynski has been found not guilty of similar charges before. Whatever happens with this case, thirty-seven years are too many, and no other cancer patient should pay hundreds of thousands of dollars for an ineffective treatment.