A couple of months ago, I discussed patient deaths at an alternative medicine clinic in Europe, where a naturopath named Klaus Ross had been administering an experimental cancer drug (3-bromopyruvate, or 3-BP) to patients outside the auspices of a clinical trial. 3-BP is a drug that targets the Warburg effect, a characteristic of cancer cells first reported in the 1920s by Otto Warburg in which the cancer cell changes its metabolism to shut off oxidative phosphorylation (the part of glucose metabolism requiring oxygen that produces the most energy) to rely almost exclusively on glycolysis and anaerobic metabolism. From a cancer cell evolution standpoint, one can understand why cancer cells would behave this way, as this change allows them to survive in environments with much less oxygen than normal cells, but the side effect of the Warburg effect is that cancer cells consume a lot of glucose for their energy needs. Indeed, positron emission tomography (PET scanning) takes advantage of this characteristic of cancer cells to use glucose labeled with positron-emitting isotope that accumulates in cells. The result is that cancer cells, which in general use a lot more glucose than normal cells, light up compared to the surrounding tissue, allowing the identification of areas suspicious for cancer. Targeting the Warburg effect is therefore a strategy to attack cancer cells preferentially.
Since I wrote about the tragic deaths of those cancer patients, I’ve been seeing stories about German alternative medicine cancer clinics popping up in my newsfeed over and over again. Intuitively, you’d think that a scientifically advanced economic powerhouse like Germany would have stricter regulations over the practice of medicine, but, the more I looked into these clinics, the more I realized that there are a lot of quack clinics in Germany every bit as quacky as any clinic in Tijuana, but with a twist. Like Mexican alternative medicine clinics, German clinics often charge enormous sums of money for treatments that range from the unproven to the dubious to pure quackery. However, in addition to the rank quackery, German cancer clinics include legitimate experimental drugs that are as yet unproven and might even only have cell culture or animal evidence supporting its potential efficacy. Indeed, 3-BP is just such an example. It is a legitimate candidate cancer drug that’s in the pipeline, having shown promise in cell culture and animal experiments, but that has human data from systematic clinical trials yet, just a handful of anecdotes when it was tried in humans under desperate circumstances. Not surprisingly, Klaus Ross’ main clinic is in Germany, and, like so many other clinics there, he was administering an as yet unapproved drug to humans.
So, prodded by a couple of recent stories from the UK, I decided to take another look at these German cancer clinics.
“Written off” by doctors and now doing well
In the world of alternative medicine cancer cures, testimonials for a treatment almost always include the patient bitterly recounting that conventional oncologists “wrote her off” before she discovered what ever miracle cure that she believes to have saved her. There are many variants. There’s the “I was given six months to live” (or one year or two months or whatever) trope, followed by the exulting that it’s now several years later and “I’m still alive.” There’s the “doctors told me to put my affairs in order” trope. It turns out, though, that the vast majority of the time, the patient’s good fortune to remain alive can be explained by the biological variability of the disease, a mistake on the doctors’ part in estimating prognosis (always a tricky and inexact art), or a better response than expected to previous treatment with conventional medicine. Sometimes, these anecdotes rely on exaggeration on the part of the alternative medicine practitioner about the odds of surviving. I’ve deconstructed more of these testimonials over the years than I can remember.
Stanislaw Burzynski, the Polish expat physician (but not oncologist) who treats patients with what he calls “antineoplastons,” is a master of this technique and several others to make it look as though he is saving lives when in fact he is not. For example, he routinely brags that there has never been anyone who has survived, for example, diffuse intrinsic pontine glioma (DIPG), and thus if there is any patient of his who survived it must be because of his antineoplastons. While it is true that the vast majority of patients with DIPG do very poorly, it is not true that none survive. There is even a registry of survivors maintained. Burzynski is also a master of exploiting diagnostic uncertainty. Because DIPGs, by definition, are located in the brainstem, often they are not biopsied because of the hazard and instead are diagnosed based on how they appear on MRI. It turns out that there are MRI abnormalities that can mimic the appearance of DIPG but are something else. Then there is biological variability. For example, deadly gliomas are indeed almost uniformly fatal within 12-18 months, but there is a “tail” to the survival curve, and patients surviving five years and beyond, while definitely not common, are not as uncommon as Burzynski would have you believe.
I mention biological variability, because another aspect of these stories that can mislead the public is that patients frequently don’t understand that not enough time has passed to say with any confidence that they are survivors. This brings us to the story of Pauline Gahan, a rather extreme and sad version of this aspect of alternative cancer cure testimonials.
Because I have Google Alerts set up for various terms related to alternative medicine and cancer, I frequently become aware of stories about alternative medicine cancer cures. Such was the case last week, when a Google Alert led me to this snippet from an interview that aired Thursday a BBC Radio 5 show, under the title ‘Why I spent 300k on “unproven” cancer treatment’ abroad’:
This is a shorter snippet from a longer interview by Emma Barnett on 5 live Daily from October 20 with Pauline Gahan, a woman who spent £300,000 at a German alternative medicine clinic to treat her metastatic stomach cancer. To raise the money, she sold her house and her car, renting her house back so that she could continue to live there. The full segment begins around the 10:25 in the three hour radio show). Unfortunately, the story is framed around the question, “What do you do when the NHS says no? What extent will you go to?” Barnett does then note that an oncologist, Professor Karol Sikora, has expressed concern about patients from the UK are spending “vast amounts of money” on experimental treatments abroad with no proof of benefit.
A celebrity testimonial
We’ll get back to the full interview in a moment, but first I have to mention another pernicious phenomenon exhibited by this interview, and that’s the celebrity testimonial for alternative cancer cures. The first one I remember covering, at least with respect to German cancer clinics, is that of Farrah Fawcett, who in 2007 sought out a German cancer clinic for “experimental” treatment of her recurrent anal cancer. Although her publicist denied vehemently that she was being treated with alternative medicine, I couldn’t help but note that she was treated at Klinik Winnerhof in Bad Wiessee, which at the time was best known for galvanotherapy, also sometimes called bio-electric therapy. Not surprisingly, it is unproven and implausible. We don’t know whether Fawcett used galvanotherapy, but we do know that she did go to a clinic best known for offering it and that ultimately she died of her disease in 2009 at the age of 62.
Before interviewing Pauline Gahan, Barnett referenced the story of British actress Leah Bracknell, best known for having played Zoe Tate in the British soap opera Emmerdale from 1989 to 2005, who was diagnosed with stage IV lung cancer recently. What brought Bracknell into the news, aside from her being a celebrity with a terminal cancer diagnosis at a relatively young age (52), is that she has been raising money to go to a German cancer clinic. The last report I saw showed her having raised £30,000 of the £50,000 needed. Indeed, Prof. Edzard Ernst wrote about her story a couple of weeks ago noting:
Why Germany? You may well ask.
Germany has long been praised by fans of alternative medicine for its liberal stance on all sorts of unproven or disproven treatments. In Britain, there are just a few physicians who are devoted to alternative medicine; in Germany, there are thousands of them. In addition, Germany has a healthcare profession called the ‘Heilpraktiker’, a poorly regulated leftover from the Third Reich. Recently, a German Heilpraktiker was implicated in the deaths of several cancer patients who had travelled from abroad to receive his treatments, because German law is more liberal in these matters than other European countries. A Heilpraktiker has not studied medicine, yet is legally permitted to make all sorts of unsubstantiated claims and treat many serious diseases with unproven therapies.
Ernst notes that the German clinic to which Bracknell wants to go is the Hallwang Private Oncology Clinic. It turns out that this is very same clinic at which Pauline Gahan is being treated. So it’s worth taking a look at this clinic, what it offers,—and what it claims.
Hallwang Private Oncology Clinic: Quackery, quackery, quackery
Upon learning the identity of the clinic where Bracknell wants to go and Gahan has gone, it befell me to fire up Safari and check out its website. Not surprisingly, the Hallwang Clinic website contains a number of very obvious red flags. For instance:
Healing-oriented and individualised medicine considers all aspects of lifestyle and not only relies on conventional treatments and recent cutting-edge developments in medicine, but also takes into account our experience in natural remedies and is open for alternative treatment options in order to work in synergy with conventional treatment strategies. We always try to be as natural as possible and as conventional as needed to achieve the best results. Integrative Health Concepts are successfully used in many diseases including malignant diseases, neurological disorders as well as in prevention and rehabilitation.
That’s nothing more than the usual blather you see on most integrative medicine websites, but take a look at what Hallwang offers: homeopathy, dichloroacetate (DCA), micronutrients and orthomolecular medicine, high dose vitamin C and other nutrients, whole body hyperthermia, ozone therapy and hyperbaric oxygen, and “many more according to your needs.”
It should hardly need to be mentioned to SBM readers that homeopathy is pure quackery, but, given that its inventor Samuel Hahneman was German, German quacks still seem to love it. I discussed DCA in the context of my discussion of 3-BP, because both drugs have a similar mechanism of action in that they both target the Warburg effect. DCA became popular among cancer quacks back in 2007 after a promising rodent study was published and made the news. Eventually, a pesticide salesman named Jim Tassano started importing DCA, which is easily synthesized, from China and other places, and selling it online. Thus was born DCA as an alternative cancer treatment. Like 3-BP, it is a legitimate experimental drug. It even has more evidence in humans that 3-BP. Unfortunately, like 3-BP, it is still thus far unproven, and its having been co-opted by quacks makes it doubtful that it will ever be validated as an effective cancer treatment. Then, of course, orthomolecular medicine and high dose vitamin C (and other vitamins) are pure quackery, as are ozone therapy and hyperbaric oxygen therapy (HBOT). HBOT has legitimate uses in burns and wound healing, but for cancer, not so much.
So what we have here is a clinic offering a variety of quackery, but there was another red flag, one that I can’t recall ever having seen on any alternative medicine clinic website before. Actually, more appropriately, it’s something I don’t recall ever having failed to see: who’s running the clinic and who the doctors are there. For instance, under Your Physicians, the website says:
We take pride in the commitment of our physicians to provide excellent care to our patients and their families.
Our team of head physicians and experienced clinical residents is specifically trained in internal and oncological medicine and lead an intensive research and academic program on cancer medicine.
That’s nice, but who are these physicians? I looked throughout the website and couldn’t find them. I did Google searches and couldn’t find out who runs Hallwang. Even the quackiest of quack clinics and naturopaths identify who runs the clinic and post short bios. The same sort of information-free blurbs can be found under Nursing Team. No, wait. There was one exception. The section on Psycho-Oncological Care shows a photo of someone named Benjamin Morlok, but not much else. Morlok has a Facebook page and a website, which identifies him as a financial coach, dream therapist, and cancer counselor. To say that I found this very odd and troubling is an understatement. Notably, Barnett also notes on her radio show that she tried to get someone from Hallwang to provide comments but that the clinic representative said that Hallwang’s policy is not to do interviews. Nor would the clinic provide evidence of how successful its treatments are. Not having any names, I was unable to find anything on PubMed published for Hallwang Private Oncology Clinic, and searching for the clinic name turned up nothing.
I was able to find a name, Dr. Jens Nolting, mentioned by patients on discussion boards here, here, and here, but I was able to find little or nothing else out about him.
Color me unsurprised.
The false cancer narrative: Hope versus the NHS
With that background, let’s circle back to the story of Pauline Gahan. First, however, let’s take a look at the sort of news coverage she’s engendered in the UK media. Here’s a sampling of typical headlines:
- Woman who was ‘written off’ by doctors in the UK is now responding well to cancer treatment in Germany
- NHS told me I was going to die of cancer… but now I’ve almost beaten the disease, thanks to treatment in Germany
- Family of terminal cancer mum “written off” by UK docs say life-saving treatment in GERMANY having “profound effect”
- Terminally ill mum close to beating cancer
- Wunderbar! German Docs Give Cancer Gran New Hope ; TERMINALLY-ILL WOMAN RESPONDS TO SPECIAL TREATMENT AFTER BEING ‘WRITTEN OFF’ IN UK
- ‘I sold my house to fund cancer treatment in Germany’
There’s another pernicious narrative buried in these alternative cancer cure testimonials that is particularly prominent in stories out of the UK, and that’s to blame the NHS for not covering unproven treatments. Basically, many of the stories are spun in such a way as to portray the NHS as cold and heartless for not paying for unproven cancer treatments, which are portrayed as the patient’s only chance to live, whether they actually are or not:
Another example is here.
Notice how at the end of each story, it’s pointed out that the Gahans will have to raise a lot more money to continue the treatments.
It’s a narrative that popped up time and time again five years ago, when there seemed to be a steady procession of British patients with incurable brain tumors raising money in a very similar way to how Gahan and Bracknell are raising money to go to the Burzynski Clinic in Houston. Story after story portrayed these patients as victims of the NHS and the NHS as being too interested in saving money to pay for Burzynski’s “experimental” treatment. Being a government entity, the NHS was also an easy target for those with a political ax to grind. Never mind that the NHS trusts are quite reasonable in not wanting to waste government funds to pay for ineffective or unproven treatments in foreign countries. In fact, it would be quite irresponsible for the NHS to do otherwise. After all, should the NHS pay £300,000 for an unproven treatment? It just doesn’t make sense.
So what treatments did Pauline Gahan undergo, anyway?
So back to the story of Pauline Gahan, as told to Emma Barnett. Basically, she was admitted to the hospital in May with leg pain after a flight home from Australia, which turned out to be due to deep venous thromboses. She suffered internal bleeding from anticoagulation, which led to an endoscopy, which found stomach cancer. She had two “operations” for her clots. It’s not clear to me what those might have been, unless she underwent thrombectomy. She even admits that the reason she had trouble walking was because of her DVTs, which meant that she couldn’t fly to Germany and instead went there in a camper van. After three weeks there, she states that she felt much better. That could partially explain the pictures of her looking so ill back in May compared to how she looks now, which is much better. She was probably fresh from her diagnosis and the procedures done on her. Be that as it may, once again, a familiar story is told. A patient receives a devastating diagnosis. She hears testimonials from a dubious clinic. She decides to go there, but it’s expensive. So she and her family sell the house and car, undertake prodigious fundraising (e.g., through GoFundMe), and go to the clinic
Having been able to find so little in various news stories and on the Hallwang website, I was actually most interested in how Gahan described her initial treatment. According to her, every day she had five or six infusions, including vitamin B, and “liver detox.” That didn’t interest me much, as it was fairly run-of-the-mill quackery that you can find at any naturopathic clinic. My main concern with the quackery is that none of it is effective for anything other than draining a patient’s wallet and that we have little idea how these treatments might interfere with the use of real medicines. Gahan also mentioned something that sounded like “renavap,” but I couldn’t quite catch it. There is something called RenaVast, which is an unapproved veterinary drug claimed to be able to treat renal disease. Somehow I doubt that’s what the clinic gave her, as she said they told her it would transiently raise her body temperature. I note that German alternative cancer clinics are very big on whole body hyperthermia, but this sounds like a half-assed attempt at it, because usually when it’s done it requires the use of whole body thermal chambers or hot water blankets. There’s also not a lot of evidence that whole body hyperthermia is an effective adjunct to treat metastatic cancer, although there are clinical trials ongoing. It is at best experimental.
Again, one of the key characteristics of German alternative medicine clinics, particularly when compared to Mexican alternative medicine clinics, is that they often combine unapproved and experimental drugs with all the quackery. (True, Mexican clinics often administer stem cell treatments.) That’s why the next part of the interview is where my ears pricked up. Gahan mentioned that her immunotherapy consisted of a drug called Keytruda (generic name: pembrolizumab). This is a member of a class of new biologics and drugs known as immune checkpoint inhibitors. It’s a drug that is FDA-approved for metastatic melanoma and metastatic non-small cell lung cancer, with clinical trials having accrued for metastatic head and neck cancer and urothelial cancer.
I recently discussed immune checkpoint inhibitors, such as drugs and antibodies targeting PD1, a key protein in the context of Vice President Joe Biden’s Cancer Moonshot initiative. Basically, drugs like Keytruda target Programmed T cell death 1 (PD-1), a membrane protein found on the surface of a class of immune cells (T cells), which, when bound to a protein known as programmed T cell death ligand 1 (PD-L1) on tumor cells, results in suppression of T cell activity and reduction of T cell-mediated immune responses. That’s why PD-1 and PD-L1 are referred to as immune down-regulators or immune checkpoint “off switches.” Targeting this off-switch, shutting it down, can reactivate the body’s immune response against the tumor. there’s no doubt that immune checkpoint inhibitors are a big deal, and this class of drugs is one of the hottest areas of research in academia and pharma today. In some cases, dramatic responses have been observed using these drugs.
On the other hand, immune checkpoint inhibitors are no panacea. Even the Cancer Moonshot report acknowledges this:
The success rates of first-generation cancer immunotherapies, such as checkpoint inhibitors, genetically engineered T cells, and new immune activators have improved remarkably over the last 10 years, resulting in durable, long-term survival—and, in some cases cures—for a subset of patients with advanced cancers such as melanoma, blood, and lung cancers. However, only 10-20% of patients with these cancers have long-term responses to current immunotherapies. We must learn why some patients who have melanoma (such as President Carter) or lung cancer respond to checkpoint blockade immunotherapy, whereas patients with many other types of adult cancers, including ovarian, breast, pancreatic, brain, and prostate cancer—as well as most pediatric cancers—have brief responses or do not respond at all.
Gahan has stomach cancer, and there is actually evidence that Keytruda is active against stomach cancer—if the cancer makes PD-L1. The Lancet recently published a phase I trial of Keytruda in gastric cancer that studied 39 patients, 36 of whom were evaluable for tumor response. Eight patients (22%) were deemed to have had an overall response, but all responses were partial. Given that gastric cancer generally doesn’t respond well to chemotherapy, these results were actually pretty good, good enough to be considered sufficiently promising to warrant phase II clinical trials. It is, however, no miracle cure, contrary to the way it’s being represented to the press, which is how Hallwang appears to have represented it to Gahan. Actually, it’s not being represented at all, because most of the news stories don’t bother to identify the immunotherapy being used at Hallwang. They just call it “immunotherapy.” It wasn’t until I actually listened to this interview that I could figure out which specific experimental treatment that Hallwang was actually using.
Hallwang also used some sort of vaccine therapy, which Gahan describes as having been made from her own DNA. It’s hard to tell what, exactly, Hallwang was doing, but it sounds like a neo-antigen vaccine. The basic idea behind such a vaccine is simple, although the production is very difficult. Tumor is collected by biopsy. Its DNA is sequenced and compared to the DNA sequence of normal cells. Mutations in the cancer cells are identified, of which there can be as few as ten or as many as thousands. Bioinformatics algorithms are then used to identify which mutated genes make cell surface proteins that could potentially serve as antigens, and peptides are synthesized in the laboratory based on the identity of those proteins to make a vaccine. The problem, of course, is that this technique is highly experimental as well, as this review article and article in the lay press show. It’s also, at least for now very expensive because of all the sequencing, analysis, and synthesis of custom peptides that are required. Basically, it’s not clear whether these vaccines will pan out.
Did Hallwang cure Pauline Gahan?
Reading this story, you might well ask the question: Did Hallwang cure Pauline Gahan? It’s a reasonable question given her glowing testimonial and apparent good health now The answer, sadly, is: Almost certainly not. I can hope that she is cured, and I can be happy that she is doing well, but my scientific knowledge of the natural history of metastatic gastric cancer tells me that she is incredibly unlikely to have been cured.
Unfortunately, the way this story has been presented is that Gahan is “almost cured.” However, remember that she was only diagnosed less than six months ago. That’s nowhere near enough time to tell if she’s even survived longer than expected. For one thing, the five year survival rate for stage IV gastric cancer is 4%. So people treated normally with conventional therapy can and do survive five years. It’s very uncommon, but it happens. In fact, Gahan has just passed her expected median survival for a woman age 55-64, roughly five months. While I can understand the Gahans’ joy that their mother is still alive, from an oncology standpoint it’s hard to be too optimistic about how she’s doing less than six months after diagnosis. Not nearly enough time has passed.
Since none of us has seen the scans and can only rely on her report that the tumors in her stomach, esophagus, and lymph nodes have disappeared and that she only has tumors left in her liver. What that means is that, after £300,000 of experimental drugs mixed with pure quackery, Gahan has had a respectable partial clinical response. In other words, she’s one of the lucky 20% or so whom we would expect to have had a partial response to Keytruda based on the study I cited above. Unfortunately, partial responses are not cures, and there’s little reason to expect that further treatment will eliminate the remaining tumors. It might, but even if that happens the most likely outcome will still be recurrence and death. We know this because we know gastric cancer is a nasty actor and that, once it’s metastasized, long term survival is very rare. Also, while there isno doubt that tumor shrinkage in response to therapy is certainly better than no shrinkage or tumor growth, tumor shrinkage often does not correlate with prolonged survival.
Perhaps the worst part of writing about these stories is having to be the voice of reality. That’s often misinterpreted as being the voice of doom, and I’m acutely aware that, should the Gahans read this, they will think I’m trying to crush their hope. In actuality, I really do hope their mother is cured and can live a long time, but that hope does not change my assessment of the Hallwang Private Oncology Clinic, which is selling false hope to desperate cancer patients like Gahan at a very high price. It doesn’t change my opinion that the Hallwang Private Oncology Clinic is engaging in very unethical behavior.
Hallwang: Combining quackery with misuse of cutting edge treatments
In thinking about the Hallwang Private Oncology Clinic and the many German cancer clinics that operate in a similar manner, I have to conclude that they are as bad as Stanislaw Burzynski, if not worse. Hallwang, for instance, doesn’t publish its results and won’t even report its results. Its Facebook page might be full of testimonials of happy patients whose lives Hallwang claims to have saved and glowing scientific reports about immunotherapy of cancer, but none of these scientific reports actually come from Hallwang.
Basically, like any good con, Hallwang asks patients to trust its doctors, to take it on faith that its protocols do what is claimed for them. It does this in order to extract large quantities of money from their wallets, even if it forces them to do things like Gahan, such as selling their houses and other valuables, taking to the Internet to raise money, and going into deep debt to pay for a combination of seemingly state-of-the-art experimental therapies that haven’t been approved or validated for what they’re being used for plus outrageous quackery. After all, believing that Hallwang is the only place that can save your life is powerful motivation to go out and raise that money. As Prof. Sikora put it later in the interview, Hallwang uses very experimental treatments in a “blunderbuss” fashion, basically throwing everything but the kitchen sink together with no sophistication. We can’t even know if these doctors know what the hell they are doing. Patients are treated, and, as far as we can tell, no systematic record of how well these patients do and how long they survive is kept, or, if such records are kept, they are kept secret.
That’s the worst thing of all. Think of it this way. What if the doctors at Hallwang and other German cancer clinics really do have protocols using experimental drugs that cure cancers that can’t now be cured and save lives that can’t now be saved by conventional medicine? Failure to publish these protocols and their results is not just unethical, it’s downright criminal because, without publication, no other patients can benefit from their protocols unless they come to Hallwang. The doctors at Hallwang basically treat their protocols as trade secrets, so that their clinic is the only place such good results can be obtained.
That’s the best case scenario. Now let’s look at the worst case scenario.
Consider another possibility about clinics like Hallwang. Their protocols don’t work any better than conventional medicine. They almost certainly don’t even work as well as conventional medicine. However, combining a “make it up as you go along” approach to the use of experimental drugs with the addition of “holistic quackery” appeals to desperate patients who want hope, are prone to believe the “best of both worlds” sales pitches, and like the idea of “individualized” treatment regardless of whether it really is or not. Publishing their true results would be a threat to their ability to charge outrageous sums of money to patients like Pauline Gahan.
Of the two possibilities, the first is criminal, and the second is even more criminal. I also know which possibility that I consider more likely.
from Science-Based Medicine http://ift.tt/2eDbbvS
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