Respectful Insolence

ResearchBlogging.orgThe silence is deafening.

Yes, I know it’s a cliche, but it’s really true this time. Last month, a major study whose results had been anticipated by the alt-med community, as well as those of us who consider it to be highly unethical pseudoscience, were reported. However, they were reported without fanfare, without press releases, without any sort of publicity whatsoever. Only a handful of bloggers who have paid attention to the issue (myself included) even noticed, and even I wouldn’t have noticed if someone hadn’t forwarded the journal article to me and asked me what I thought of it. So under the radar is this important paper that not a single alt-med website that I’ve been able to find has commented on it, even nearly four weeks after its release.

I wonder why.

I suspect that you’ll soon understand why. The study is of an “alternative” medical therapy for pancreatic cancer, one of the most lethal, if not the most lethal, cancer there is. There are several reasons for the lethality of pancreatic cancer. Less than 5% of all patients diagnosed with pancreatic cancer are alive five years after diagnosis. To put it another way, pancreatic cancer is the tenth most commonly diagnosed cancer but number four in the list of cancer killers. That’s because most (at least 80%) are diagnosed with unresectable and/or metastatic disease, for whom surgery cannot be performed. Given that the only currently known possible chance of long term survival in pancreatic cancer comes from a complete surgical resection of the cancer with negative surgical margins (i.e., no tumor at the margins of the surgical specimens and a rim of normal tissue between the margin and the tumor), any pancreatic cancer patient who is not a candidate for surgery has incurable disease. Of the minority of patients who do have their cancer completely resected surgically, the five year survival rate is better, perhaps in the range of 15-20% or so, but still the vast majority will be dead within five years, usually much less. Moreover, known as a pancreaticoduodenectomy or Whipple procedure, the surgery necessary to remove a pancreatic cancer in the head of the pancreas (the most common location) is a huge operation that involves removing the head of the pancreas and the duodenum and then reconstructing the connections between the bile and pancreatic ducts and the GI tract and establishing continuity between the stomach and small intestine. It’s a tour de force operation that often takes 8 hours or more and is fraught with the potential for complications, both short term and long term. However, for someone with a potentially resectable pancreatic cancer in the head of the pancreas, it is the patient’s only hope. Even so, after surgery, median survival times still only range from 12 to 19 months.

Because the outlook for pancreatic cancer, particularly unresectable pancreatic cancer is so grim (the median survival has barely budged from less than six months for decades. Median survival for untreated metastatic pancreatic cancer is on the order of 3-4 months, although gemcitabine chemotherapy regimens combined with radiation) can result in median survivals of six months or more. For locally advanced pancreatic cancer that cannot be resected but has not metastasized, the median survival is on the order of 6-12 months depending on the study. Thus, we can rightly say that pancreatic cancer is one of those cancers for which science-based medicine has frustratingly little to offer that can cure it. That’s not to say that science-based medicine doesn’t have a lot to offer for palliation, but no one wants just palliation. We all want to live to a ripe old age, not just have our pain and nausea palliated for a few months before cancer claims us. Even scarier is that pancreatic cancer usually produces few or no symptoms until it is fairly advanced. Usual symptoms include vague upper abdominal discomfort, loss of appetite, and post-prandial nausea from intermittent gastric outlet obstruction, you know, the sorts of symptoms that nearly of us have from time to time and that primary care doctors see in their practice every day. By the time a pancreatic cancer causes severe pain or obstructs the bile duct leading to jaunice, it’s usually unresectable or metastatic. (Often the reason it causes such severe pain is because it invades a plexus of nerves just posterior to the pancreas.)

It is the very deadliness of pancreatic cancer and the lack of effective life-saving or life-prolonging treatments for it that make pancreatic cancer a ripe condition for quackery. Rising above most other quackeries to attract a lot of attention about a decade ago is a quackery known as the Gonzalez protocol. It is described on Dr. Nicholas Gonzalez’s website as involving dietary changes, supplements, the replenishment of pancreatic proteolytic enzymes, and “detoxification,” including coffee enemas. It is not an easy therapy to undergo. For example, Dr. Gonzalez states:

Overall, cancer patients will consume 130-175 capsules a day, including nutrients as well as enzymes. Non-cancer patients might consume in the range of 80-100 capsules a day, the exact number depending on their health status and medical problems.

I know of no science-based cancer protocol that requires a patient to consume 150 pills a day. There are also the dietary alterations that can be quite hard to follow, as well as the frequent coffee enemas. All in all, the Gonzalez protocol is an arduous regimen for a debilitated pancreatic cancer patient to follow. Still, for some reason, it gained some popularity in the “complementary and alternative medicine” (CAM) community, so much so that, based on poorly designed case series of eleven patients, Dr. Gonzalez managed to get a clinical trial funded by the NIH to study his method versus standard chemotherapy, a sordid story that Dr. Atwood has chronicled in detail in a long series of blog posts. That trial ended in 2005.

So why is it 2009 before we have the results of this trial, which show that the Gonzalez protocol is worse than useless? As Gollum would say, “It makes us wonder, yes it does.” The trial, begun in 1999, is known formally as Prospective Cohort Study of Gemcitabine Versus Intensive Pancreatic Proteolytic Enzyme Therapy With Ancillary Nutritional Support (Gonzalez Regimen) in Patients With Stage II, III, or IV Adenocarcinoma of the Pancreas. The results were finally reported in an E-pub ahead of print manuscript for the flagship journal of the American Society of Clinical Oncology, the Journal of Clinical Oncology, and entitled Pancreatic Proteolytic Enzyme Therapy Compared With Gemcitabine-Based Chemotherapy for the Treatment of Pancreatic Cancer, written by John A. Chabot, Wei-Yann Tsai, Robert L. Fine, Chunxia Chen, Carolyn K. Kumah, Karen A. Antman, and Victor R. Grann. It is a clinical trial studying fairy dust versus science in treating a horrific disease.

Sadly, the “scientific” rationale behind the Gonzalez protocol, with its megadoses of supplements and pancreatic enzymes plus “detoxification” by coffee enemas, is a perfect example of what Harriet Hall terms “Tooth Fairy science.” The Gonzalez treatment is basically a modification of a protocol known as the Kelley Treatment, which in turn was very similar to the Gerson protocol. In any case, it’s all an example of how alties have this conception that disease is caused by “toxins” and “contamination” that must somehow be purged in a religious ritual of colon cleansing. I’ve joked about this before as being an example of when mere regularity is not enough and mocking late night infomercials about colon cleanses, but, totally serious, Chabot writes in the introduction to this study:

The Scottish embryologist John Beard first proposed pancreatic proteolytic enzyme treatment in 1906 and soon after published a monograph, entitled The Enzyme Therapy of Cancer. In 1981, Nicholas Gonzalez began to evaluate the use of proteolytic enzyme therapy. Twelve years later, in 1993, he was invited to present a series of cases at the National Cancer Institute (NCI), which led him to undertake a case series of alternative medical therapy that included proteolytic enzymes, diet, nutritional supplements, and detoxification procedures. Among 11 patients with inoperable, biopsy-proven, stages II to IV pancreatic adenocarcinoma, he reported 81% survival at 1 year and 45% at 2 years. Four of the 11 patients survived for 3 years.

This is the very example of an implausible hypothesis. True, it’s not as implausible as homeopathy (few hypotheses are), but it goes against everything we know about cancer in general and pancreatic cancer in particular. There is no evidence that pancreatic enzyme deficiency has anything to do with pancreatic cancer, for example. Nor is there any evidence that this discription of the rationale behind the Gonzalez protocol, cribbed straight from the NCI website, has any relationship to reality:

Two major concepts underlie use of the Gonzalez regimen in cancer treatment. The first concept is that the pancreas, like the liver, is an organ that performs a detoxification function and that pancreatic enzymes help the body eliminate toxins and help normal cells repair damaged cells.[2] The second concept is that cancer and most other human illness are related to physiological imbalances created by environmental toxins either consumed in food or contacted in the environment.[2,3]

Proponents of the Gonzalez regimen believe that toxins from sources such as processed foods and environmental pollution are responsible for human cancers. These toxins are thought to accumulate in tissues and over time create imbalances in the autonomic nervous system, diminish the normal immune response, and give rise to cellular damage that can lead to cancer.[2,3] If these toxins could be neutralized and eliminated from the body, proponents believe, both early and established cancers would be halted, and general health would be restored.[2,3]

Here’s the problem. These “toxins” are never identified, nor is there any evidence that the Gonzalez regimen actually removes them. It’s not that environmental exposures don’t have an effect on cancer susceptibility. Smoking can cause lung cancer and, ironically enough, increase the risk of pancreatic cancer as well. “Detoxification” quackery like the Gonzalez protocol takes science and turns it into Tooth Fairy science by giving near magical characteristics to these “toxins.” In any case, cancer is primarily a genetic disease. Even heavy smokers who smoke for 50 years “only” have about a 25% lifetime risk of developing lung cancer, which means more smokers don’t get lung cancer than do. In any case, think about it: Let’s say there is this host of unnamed, undefined “toxins” that give you pancreatic cancer. Remember, the toxins from tobacco smoke that predispose to lung cancer are largely known and quantifiable. Why would one think that coffee enemas would remove those “toxins”? Certainly there is no scientific basis to think that the special diet, the dozens of capsules of supplements and pancreatic enzymes, or the other aspects of the regimen would “detoxify” anything. Basically, the Gonzalez protocol appears to derive from a prescientific notion of disease that is almost religious in its nature blaming “contamination” as the cause of all disease and that one must “purge oneself” of this “contamination” to cure the disease.

But, say Gonzalez supporters, what about the case series of 11 patients with stage II to IV pancreatic cancer from the 1990s reporting 81% survival at 1 year and 45% at 2 years, with 4 of the 11 patients surviving for 3 years? As Dr. Kimball Atwood pointed out, this was a nonconsecutive case series, a so-called “best case” series. Basically, it’s a cherry-picked series, and I’ve criticized “best case” series before because they in essence intentionally look at outliers for whom the therapy may or may not have made a difference. Some patients with pancreatic cancer do survive longer than a year. Indeed, actor Patrick Swayze is one such patient, who has now been alive over a year and a half since being diagnosed with stage IV pancreatic cancer with liver metastases. Without knowing the denominator (i.e., how many patients Gonzalez treated to produce those 11 patients with significantly better than average survival for pancreatic cancer), his case series is meaningless. Indeed, back in my old Usenet days in the late 1990s and early 2000s, I would frequently comment that if I were to apply for a grant at the NIH to fund a clinical trial based on such a thin gruel of preliminary data, my application would have found its way to the cylindrical file. The trial for the Gonzalez protocol did not. Selection bias is a wonderful thing if you’re peddling unscientific cancer therapies, where patients who actually could undergo the rigorous Gonzalez protocol would be more likely to be doing better and thus more likely to continue to do better than average, therapy aside.

So what was this trial? These were the objectives:

  1. Compare the survival of patients with stage II, III, or IV adenocarcinoma of the pancreas treated with gemcitabine versus intensive proteolytic enzyme therapy and adjunctive dietary and nutritional support.
  2. Compare the quality of life in patients treated with these regimens.

The two arms of the study were described thusly:

This is an open-label study. Patients are stratified according to stage (II or III vs IV), performance status (0-1 vs 2) and nutritional status (well nourished or moderately malnourished vs severely malnourished). Patients are entered into 1 of 2 treatment arms at their choice:

  • Arm I (Nutritional Arm): Patients receive pancreatic enzymes orally every 4 hours and at meals daily on days 1-16, followed by 5 days of rest. Patients receive magnesium citrate and Papaya Plus with the pancreatic enzymes. Additionally, patients receive nutritional supplementation with vitamins, minerals, trace elements, and animal glandular products 4 times per day on days 1-16, followed by 5 days of rest. Courses repeat every 21 days until death despite relapse. Patients consume a moderate vegetarian metabolizer diet during the course of therapy, which excludes red meat, poultry, and white sugar. Coffee enemas are performed twice a day, along with skin brushing daily, skin cleansing once a week with castor oil during the first 6 months of therapy, and a salt and soda bath each week. Patients also undergo a complete liver flush and a clean sweep and purge on a rotating basis each month during the 5 days of rest.
  • Arm II (Chemotherapy Arm): Patients receive gemcitabine-based chemotherapy.

Quality of life is assessed at 0, 2, 6, and 12 months and then yearly thereafter.

Patients are followed at 1, 3, 7, and 12 months and then yearly thereafter.

Arm I is the very epitome of Tooth Fairy science. Indeed, it’s pure fantasy. How such a study was ever approved by an Institutional Review Board, I’ll never know. It is to the shame of medical academia that it ever was.

However this misbegotten parody of a clinical trial came into existence and somehow managed to slime its way into being funded and accruing patients, a word needs to be said about the design of this study. It is not randomized, and it is not double-blinded. It was originally designed as a randomized but not blinded study, given the difficulty in blinding which group is getting coffee enemas, for example, and which were not. (I can see how placebo enemas would be a problem.) Even so, because placebo effects would not be evident in the objective outcome, namely survival, this would not be a major problem in a study of this sort, although the lack of blinding could conceivably affect the quality of life measurements. Unfortunately, investigators could only accrue three patients between 1999 and 2001; so in 2001, the trial protocol was converted from a randomized phase III design to an open label observational design. Basically, patients picked which therapy they wanted, and the investigators prospectively studied how they did. The figure below shows the ultimate flow of patients:

i-0cb2f39d3e07f87677c4e44c8948c069-Pancreatic Proteolytic Enzyme Therapy Compared With Gemcitabine-Based Chemotherapy-3.jpg

One serious problem with a nonrandomized design like this is the likelihood of selection bias. In this case, it would be “self-selection” bias in that investigators would have to worry whether patients who were either worse off or better off might opt preferentially for one arm of the trial over the other. I will address that point after we look at the results, which are quite striking:

i-712a95c74b1ff17c83018468a629a896-Survivalgraph.jpg

In words:

At enrollment, the treatment groups had no statistically significant differences in patient characteristics, pathology, quality of life, or clinically meaningful laboratory values. Kaplan-Meier analysis found a 9.7-month difference in median survival between the chemotherapy group (median survival, 14 months) and enzyme treatment groups (median survival, 4.3 months) and found an adjusted-mortality hazard ratio of the enzyme group compared with the chemotherapy group of 6.96 (P <.001). At 1 year, 56% of chemotherapy-group patients were alive, and 16% of enzyme-therapy patients were alive. The quality of life ratings were better in the chemotherapy group than in the enzyme-treated group (P <.01).

Moreover, the quality of life, as measured by standardized surveys, was actually worse for the Gonzalez therapy group:

Patients in the two groups responded similarly to the questionnaires on quality of life before initiation of therapy, but the overall FACT-PA scores during 12 months decreased more in the enzyme group than in the gemcitabine group (Fig 3). Twenty-four percent of total measurements were missing. Quality of life scores of both groups were significantly different (P .01). During the first 6 months of the study, pain scores increased in the enzyme group, but they decreased in the chemotherapy group (P .05); however, few patients reported on use of analgesics. (Table 2).

In all my years in medicine, surgery, and surgical oncology, I have never seen a study with such a striking difference in outcome between the two groups. No wonder the Office for Human Research Protections (OHRP) issued a determination letter stating that it was appropriate to terminate the study before the full 72 patients were enrolled due to the study having reached its “predetermined stopping point.” These days, clinical trials are designed with periodic assessment of results and predetermined stopping points. These stopping points are invoked to shut down the trial in the event that one group is doing so significantly better than the other that enrolling the remaining patients could not possibly change the result. The purpose of such a stopping point is to protect clinical trial subjects from being enrolled in a study that no longer has clinical equipoise; i.e., the groups can no longer be predicted to have roughly equivalent outcomes based on what we know. Usually, it’s the experimental group that does better than the control group. At least that’s the intent. Sometimes, however, as in the case of the Gonzalez protocol, it’s the experimental group that does much worse, so much so that the study has to be halted before reaching its full accrual.

But it’s even worse than that. Not only was the median survival of patients in the Gonzalez therapy group worse than it was for the standard chemotherapy group, it was three times worse. At one year, 56% of the chemotherapy patients were alive; only 16% of the Gonzalez protocol patients were. But it’s still even worse than that for the Gonzalez therapy. Not only did Gonzalez therapy patients do worse than those receiving standard therapy, but they did worse than the “average” pancreatic cancer patient as determined by the survival curve derived from data from the SEER Database. The most likely reason to explain such a result is that the Gonzalez therapy is not just inferior to gemcitabine but is probably completely biologically inactive against pancreatic cancer. What we are looking when we examine the survival curve for the Gonzalez protocol group is, most likely, indistinguishable from a survival curve of untreated pancreatic cancer versus treated.

Is this study a slam dunk? Is the Gonzalez therapy, for all intents and purposes, as dead as the parrot in a Monty Python sketch? Or is it still pining for the fjords? Personally, I’d say that this study is proof positive that, as far as having any use whatsoever in pancreatic cancer, the Gonzalez protocol has shuffled off ‘its mortal coil, run down the curtain and joined the bleedin’ choir invisible.

That’s not to say there aren’t a few problems. First and foremost, the nonrandomized nature of the trial makes it possible that biases crept in. As I mentioned before, that is always a potential problem with a nonrandomized study design, especially one in which the patients can select which group they want to be in. Fortunately, the patients in each group ended up being reasonably well matched in age, gender, and other demographics. There was, however, at least one relevant difference that no one discussed. Indeed, I’m surprised that the investigators didn’t mention it, as it could have at least partially suggested a reason why the Gonzalez group might have done so poorly early on. It’s unlikely to have made a difference big enough to have explained the huge difference between patient groups, but it would at least have been a straw to grasp at. Specifically, the serum albumin levels in the Gonzalez group were statistically significantly lower than they were in the control group. Albumin is a rough estimate of nutrition (although there are better parameters) and we surgeons know that lower albumin levels are associated with increased early mortality in pancreatic cancer. I doubt that this is anywhere near enough to explain such a huge difference in mortality between the two groups, especially since the difference between the albumin levels in the two groups was relatively small (4.3 g/dL versus 4.0 g/dL), with the Gonzalez group still having albumin levels within the normal range, but it is one difference that caught my eye. It is also likely (but not well explained) that there were differences in supportive care, such as the rate of inserting biliary stents to relieve bile duct obstruction or aggressively treating infections such as ascending cholangitis, which is one of the most common causes of death in pancreatic cancer patients. The obstructed bile duct causes bile to back up; the bile gets infected; and the patient develops a life-threatening infection. The primary treatment is biliary drainage, either through a tube inserted endoscopically into the bile duct or inserted through percutaneously into the bile ducts in the liver. Antibiotics are necessary, too, of course, but they don’t do much good without biliary drainage. Also, if there was a difference in palliative care between the two groups, that, too, would be yet another example of the unethical nature of this trial.

The one thing that surprised me about this study was not so much that the Gonzalez group had the same mortality and median survival as, in essence, untreated pancreatic cancer patients (which they are), but rather that the survival in the gemcitabine group was so long (14 months). This is better than most studies of gemcitabine-based regimens from the time period during which patients accrued to this study (although results of more recent trials have been better). This suggests a possibility of some unexpected selection bias. Alternatively, it could be that this is simply an outlier group. However, it’s highly unlikely that it invalidates the study. Given the striking difference between the two groups and the fact that the Gonzalez group did more poorly than historical controls, from this study we can confidently say that the Gonzalez protocol is almost certainly no better than no treatment.

In fact, it’s probably worse. Go back to Dr. Atwood’s post on this issue and consider the story of an unfortunate 40 year old man who enrolled in the trial and chose the Gonzalez protocol arm. This man was told to have his fillings removed and afterward tried as hard as he could to continue the regimen to the letter and suffered horribly as he did. At one point he was even told that increasing pain might be an indication that his tumors were “dissolving.” Although it may be that the Gonzalez protocol didn’t make his pain worse, it’s quite clear that the man’s pursuing the therapy kept him from persuing effective palliative care that might have made his last few months on this earth a lot less unpleasant. Indeed, this makes me wonder what the investigators did after the trial was closed. From an ethics standpoint, every patient in the Gonzalez arm should immediately have been informed of these results and been strongly encouraged to give up the Gonzalez protocol and undergo standard gemcitabine chemotherapy.

Finally, the most disturbing issue that this trial raises is the question of why it took nearly four years after the trial was stopped to publish the results. Dr. Atwood has speculated why this might be the case, namely to cover up the results that were unfavorable to Gonzalez. There is now no doubt that this trial was completely unethical right from the very beginning, but that lack of ethics was compounded by not having the results reported right away. In this, after having had a few days to think about it, I am going to have to strongly disagree with Dr. Atwood when he asserted, “A compelling argument can even be made that the JCO should not have published the report–as paradoxical as that sounds.”

I can understand where he’s coming from. This study clearly violates the Helsinki Declaration, to which JCO requires the clinical trials that it publishes to adhere. However, I find an it equally, if not more, compelling to take the view that the patients who suffered in the Gonzalez group will have suffered in vain if the results of this trial were not published. I also tend to take the view that shining a light on such a trial, in the form of publication, is a good thing in this particular case because it eliminates the uncertainty over whether the results were as bad as we know them to be. Let’s put it this way: If the results were not published in a peer-reviewed journal but rather announced or mentioned in a report, they would seem less credible to shruggies. It is these people who need these bad results rubbed in their noses, the better to let the stench waft into their nasal passages and make them retch. When they ask, “What’s the harm,” we can tell them in no uncertain terms what the harm is. The same would apply if they were simply announced on ClinicalTrials.gov or mentioned in a report. It’s just not the same as a peer-reviewed publication in one of the highest impact oncology journals there is. This is truly a case where the greater good can be served by disseminating this data far and wide as soon as possible by the most scientifically credible means necessary.

One thing that is most remarkable is that this study was released without any fanfare whatsoever. You can bet that, had the results been positive, it would have been trumpeted with press releases. I bet that even if the results had shown that the Gonzalez protocol was no worse than “conventional” therapy, it would have been trumpeted as “Gonzalez therapy as good as conventional chemotherapy!” to the press. Yet, here we have exceedingly striking results, results far more striking that we usually see in any clinical trial, cancer or otherwise and what do we hear?

Nothing.

Well, not quite nothing. H. Kenneth Schueler, writing for Ralph Moss, who is a booster of the Gonzalez therapy and was involved in the genesis of this clinical trial, has commented in a post entitled Clinical Trial of Pancreatic Enzymes: One View. He actually seems to accept the trial results, sort of. After pointing out that it is not surprising that an advanced cancer would require chemotherapy, he tries to rationalize away some of the differences in quality of life observed in the trial but in the end more or less accepts the trial results. More typical to me is how Schueler sidesteps the horrific disaster that is this trial and starts complaining that it’s wrong to view its results as scientific medicine trumping “alternative” medicine (which is actually exactly right; scientific medicine did trump alternative medicine in this trial):

Several of my physician friends have told me two lessons they learned during medical school: never say anything publicly that is so far outside the box you could be labeled a “quack”. Secondly, you will rarely get a research grant for a non-patentable drug-pharmaceutical companies have no interest in testing any drug they can’t obtain exclusive rights to. So basically, that would have eliminated Ignaz Simmelweis’s radical idea in 1847 of washing hands with chlorinated lime solutions before obstetrical deliveries to reduce the 10-35% infant mortality caused by Puerperal fever. It also would have prevented the bold discovery by Dr Barry J. Marshall and Dr J. Robin Warren of Australia of H. Pylori bacteria as the cause for duodenal and gastric ulcers and stomach cancer, and it’s eventual treatment with antibiotics. When Marshall and Warren first presented their research 25 years ago, they were ridiculed by colleagues. But they were proven correct and in 2005 they jointly received the Nobel Prize.

Ah, yes, the old Galileo/Semmelweis/Marshall/Warren gambit. As if we haven’t heard that before. Of course, it’s a myth that Marshall and Warren were treated so poorly. In fact, the acceptance of H. pylori as a major cause of duodenal ulcers happened in record time. Within less than a decade, the standard of care for duodenal ulcers radically changed. I lived through this transition. It was fast, and it was based on overwhelming evidence. In other words, it was a triumph of science-based medicine. Compare that to CAM, where centuries-old concepts still prevail, unaffected by a hundred years of scientific medicine.

Schueler’s conclusion? To try to coopt the language of science:

There is a growing consensus amongst Integrative Oncologists that for patients with metastatic cancer, the most effective approach to substantially increase survival is a cocktail regimen incorporating a group of therapeutic agents which simultaneously and synergistically target multiple tumor cell mechanisms…

No duh. That’s what real oncologists are increasingly beginning to believe, too. That does not mean that “integrating” pseudoscience with science will necessarily result in better outcomes. I know where Schueler’s going with this. He’s going to argue that various forms of woo target different tumor growth mechanisms or that herbal remedies are better because there’s more stuff in there, again, to target different tumor mechanisms, but his is an evidence-free assertion. As I’ve said many times before, show me the evidence, or, as I put it when I’m in one of my cruder moods, evidence talks, bullshit walks, and Schueler’s assertion, without solid evidence to back it up, is nothing more than bullshit.

It is a smelly load that I suspect we’ll be seeing and hearing a lot of once CAMsters finally figure out that they can’t ignore this study any more. I suspect that will happen when the study actually sees physical print. It’s fairly easy to ignore an E-pub that comes out weeks or months before the physical article, but harder to do so when the article comes out. I’ve seen articles where no press release accompanied the electronic publication but did accompany the print release, and I’ve even seen articles where press releases were issued months after the study was published.

My guess, however, is that there will be no press release and no accompanying editorial. The authors, I suspect, are embarrassed by the results that they want as little attention as possible, which is why I plan on keeping an eye out for the print publication and updating this post when that happens.

REFERENCE:

John A. Chabot, Wei-Yann Tsai, Robert L. Fine, Chunxia Chen, Carolyn K. Kumah, Karen A. Antman, & Victor R. Grann (2009). Pancreatic Proteolytic Enzyme Therapy Compared With Gemcitabine-Based Chemotherapy for the Treatment of Pancreatic Cancer Journal of Clinical Oncology : 10.1200/JCO.2009.22.8429 (E-pub ahead of print).

Comments

  1. #1 techskeptic
    September 14, 2009

    Just heard about this at the NECSS meeting for the first time. thanks for providing the extra detail.

  2. #2 Militant Agnostic
    September 14, 2009

    Orac on “shruggies”

    It is these people who need these bad results rubbed in their noses, the better to let the stench waft into their nasal passages and make them retch. When they ask, “What’s the harm,” we can tell them in no uncertain terms what the harm is.

    Magnificent Insolence

    I would think the coffee enemas alone would be enough to tip the quality of life balance in favor chemotherapy.

  3. #3 MikeMa
    September 14, 2009

    I wonder if we’ll see any of the usual crazies here on this one. The denunciation of the CAM therapy is pretty thorough and conclusive. Orac’s post on that study was, as usual, elucidating and complete. It seems hard to deny the rejection but the likes of Silly Sue and Dr Jay have rallied before.

    I’ve never had a coffee enema or chemo and I’m glad not to have to choose between them. Both sound terrible but chemo is clearly the way to go if you want to have even the smallest chance at life.

  4. #4 Roger Federer
    September 14, 2009

    The cancer pancreatic, a common form of cancer is a disease in which cells are cancerous (malignant) in the tissues of the pancreas. Cancerígenasno If these cells are treated or removed, over time can lead to a tumor, which can interfere with the proper functioning of the colon or rectum and spread to cause cancer in other parts of the body, so findrxonline indicates in his article on this disease. The cause for which the colon cancer is still unknown but there are certain risk factors that appear to favor disease: Risk common after 40 years of age for both men and women: Polyps in the rectum, cancer everywhere agency, or granulomatous Colitisulcerosa, for immunodeficiency diseases, Crohn’s disease. The type of diet seems to play an important role, since it occurs in people who eat little fiber, high cantidadesde proteins, fats and refined sugars, as well as smoking, certain chemicals, radiation and so on.

  5. #5 JJ
    September 14, 2009

    This video uses rap to convey some of the finer points of the Gonzalez protocol:
    http://www.youtube.com/watch?v=qr0ZS3YjBbs

  6. #6 Helena Constantine
    September 14, 2009

    All a press release is an e-mail sent to a list of reporters. Why Don’t you make one?

  7. #7 James Sweet
    September 14, 2009

    This is neither here nor there, but that graph gives me the willies. I was parsing it in my usual I’m-an-engineer-I-love-graphs kind of way, and suddenly I realized the reason it was so bumpy is because each downward notch represented a person succumbing to cancer.

    I suppose as an oncologist, you deal having to read that kind of graph all the time Orac. I don’t envy you.

  8. #8 HealthEd
    September 14, 2009

    On behalf of my fellow Brown University alums, I apologize that Gonzalez was unleashed upon the world. But at least he only studied English Lit at Brown. (He must have done well, too, considering his propensity with fairy tales and magical thinking.) According to his CV, he got the MD from Cornell.

    I was curious about stuff in the “Statements of Support” section of his website, where he claims funding from P&G and Nestle. What up with that? There’s even this claim, from a former (and skeptical) Pasteur Institute medical director: “Additionally, never did I see an instance where his treatment harmed people.” I guess the new study blows that out of the water.

    And Orac, thanks for taking a very complex subject and making it completely interesting and palatable to a humanities major. (So easy a caveman can understand it?)

  9. #9 Prometheus
    September 14, 2009

    After reading the details of the “protocol”, I think I have an idea why the patients in the “CAM” arm reported a lower quality of life.

    Patients receive magnesium citrate and Papaya Plus with the pancreatic enzymes.

    Magnesium citrate causes a pretty profound diarrhea in people without cancer – I can only imagine what it did to the poor people in this study. Also, what was the plan for patients with bowel obstructions?

    Additionally, patients receive nutritional supplementation with vitamins, minerals, trace elements, and animal glandular products 4 times per day on days 1-16, followed by 5 days of rest. [Emphasis added]

    What, exactly, did they mean by “animal glandular products”? Were they referring to “sweetbreads” (thymus and pancreas)? Or are they giving pancreatic juices, dried thyroid, etc.? I think I’d need a rest, too, after 16 days of that.

    Courses repeat every 21 days until death despite relapse.

    I think that pretty much sums it up.

    Patients consume a moderate vegetarian metabolizer diet during the course of therapy, which excludes red meat, poultry, and white sugar.

    What is a “metabolizer diet”? “Non-metabolizer” would be nice euphemism for “dead”.

    Coffee enemas are performed twice a day, along with skin brushing daily, skin cleansing once a week with castor oil during the first 6 months of therapy, and a salt and soda bath each week.

    Twice-daily coffee enemas would do a lot to bring down my “quality of life”, even though I am in good health. The skin brushing sounds like something that could also get tiring – anybody know what possible rationale there was for including that? And “cleansing” the skin with castor oil also seems to lack a viable rationale. The salt and soda baths might be refreshing, but I fail to see how they might affect pancreatic cancer. I guess I lack “vision” (i.e. the ability to permanently suspend disbelief).

    Patients also undergo a complete liver flush and a clean sweep and purge on a rotating basis each month during the 5 days of rest.

    Again we have that extremely vague term “liver flush” – how, exactly, do they “flush” the liver? I envision them hooking up a garden hose to the inferior vena cava and turning on the tap. And what is a “clean sweep and purge”?

    In my evaluation of this study, I first tried to imagine what the Insitutional Review Board (IRB) of my university would have to say about the study design. My imagination not being up to the task, I ran the “Gonzalez arm” of the study by one of the members (at lunch). Her response was – and I quote – “Not f*****g likely!” When I showed her the paper, she was astounded. I suppose things are different at a large, famous university like Columbia.

    Secondly, I tried to picture what the editors and reviewers of some of my favorite publications (Cell, Virology etc.) would say if I sent in a paper with methods like this. Usually, even the best studies get a few paragraphs of comments and suggestions; more mundane studies can get pages of questions, comments and suggestions. I suspect that this study would have received only a single sentence: “You’ve got to be kidding!”

    I’m of two minds about this study. On one hand, I agree with Dr. Atwood that this study should have been rejected – by the IRB, by the editors and by the reviewers. On the other hand, it is important that at least a few of these nonsensical “protocols” be investigated and the results published, to give doctors some solid data to show patients inclined to try coffee enemas over chemotherapy.

    I would suggest that the next “investigation” of the “Gonzalez protocol” be done by the Office of Research Integrity.

    Prometheus

  10. #10 D. C. Sessions
    September 14, 2009

    So far the MHA response has been one (1) reply by James Panozzi (who occasionally posts here) concluding that although the Gerson protocol looks like a loser, we should press on with investigating other alternative protocols [1] to find one that works.

    [1] Panozzi is a big fan of homeopathy, so throwing Gerson under the bus is not altogether surprising.

  11. #11 luna1580
    September 14, 2009

    uhm, if we now have shown that this gonzalez “protocol” does nothing to increase survival rates and decreases quality of life shouldn’t it be made illegal? if not on the grounds that it is fraud to say it extends survival rates, then what about on the grounds that it is harmful “medicine”, like a faulty pharmaceutical?

    and i know desperate and misinformed people would still go to border-town woo “clinics” to partake in it if it was banned in the states, so isn’t the most important thing to somehow help this get into the popular press and into the minds of the public before they become cancer patients?

  12. #12 Kismet
    September 14, 2009

    The protocol is really, really bizarre. I can’t imagine how they came up with a rationale for most of that stuff.
    Prometheus, are you sure about the magnesium citrate? I think at doses at, around or below the upper limit (350mg) it shouldn’t cause diarrhea…

    I like your other posts ORAC, but your cancer posts are even better.
    You are teh god of cancer blogging (ok, you’re the only person regularly blogging about cancer that I can think of but your still the best!)

  13. #13 IBY
    September 14, 2009

    That study is so unethical. How the hell did it get approval?! Jeez, the coffee enema alone would make me gag at the thought of the study.

  14. #14 Prometheus
    September 14, 2009

    Kismet comments:

    Prometheus, are you sure about the magnesium citrate? I think at doses at, around or below the upper limit (350mg) it shouldn’t cause diarrhea…

    That is absolutely correct. I made the assumption that the “Gonzalez Protocol” – since it is so outrageous and excessive in every other aspect – would include doses of magnesium citrate sufficient to perform a pre-colonoscopy bowel prep.

    On further reflection (prompted by Kismet), I realise that it probably doesn’t use such a high dose (I hope).

    Still, someone who thinks that coffee should go in through the wrong end of the alimentary canal is capable of anything.

    Prometheus

  15. #15 MikeMa
    September 14, 2009

    IBY,
    If the coffee enema makes you gag, you are doing it wrong :)

  16. #16 Tsu Dho Nimh
    September 14, 2009

    I can think of reasons for the high death rate: Exhaustion and unrelenting pain, complicated by malnutrition because they were to damned sick to eat.

    Those poor people were slaves to a schedule of pills, enemas, baths, liver flushes and the FSM knows what else. They were (if the protocol was followed correctly) denied pain relievers that are normal for cancer patients. They were on a restricted diet, and because of the medications and schedule, they couldn’t eat when they were actually hungry.

    Here’s a suggestion – let’s take 30 healthy alternative medicine proponents and run them through the Gonzalez regime for a year and see what it does to them.

    My father died of cancer – on a morphine pump, eating what and when he wanted to, getting his coffee by the normal route, sleeping when he could, not tortured to death by pill-pushing fanatics.

  17. #17 Rjaye
    September 14, 2009

    Well, this is off topic, but related. It was just reported that Patrick Swayze died today. He had pancreatic cancer.

  18. #18 T. Bruce McNeely
    September 14, 2009

    Perhaps, in this time of trouble, Dr. Gonzales would find Dr. Jay Gordon’s response useful:

    My experience is more valuable than your 14 slanted poorly-executed studies.

  19. #19 Joseph C.
    September 14, 2009

    It was just reported that Patrick Swayze died today.

    Bummer. I felt really bad for him whenever I’d see the tabloids exploiting his illness at the supermarket check out lanes.

    How long before Mike Adams shits out another tasteless rant about how Swayze didn’t have to die, was poisoned by “Western” medicine, etc?

  20. #20 DLC
    September 15, 2009

    I looked at the graph of survival and thought: “Holy Shit, the Gonzales “treatment” makes them die faster !”
    I put treatment in quotes, because the description — 150 pills, laxitives, coffee enemas — reminded me of the old slang “give him the treatment!” which meant to beat the living hell out of. I hope I never get pancreatic cancer, but if I do, I’m ice-picking the fist SOB to come at me with a coffee enema.

    PS: on a sad note: actor and pancreatic cancer patient Patrick Swayze died today. He was 57, and fought his cancer with the best available science based medicine.
    I wish to offer my condolences to his family and friends.

  21. #21 Judith
    September 15, 2009

    I know personally of two people cured of Stage 4 cancer with the enzymes and enemas.

    Keep believing those doctors to tell you what I presume want you want to hear… “I can cure your cancer.” The Dr’s make more money from you when you have cancer. They love it and when you walk in with cancer they see a new house or a new Mercedes. 60-70% of cancer patients eventually die from the chemo and results. Look at the statistical results of chemo which are probably skewed to make it look even better for them.

    They talk about the greed of Wall Street…how about the greed of doctors that are paid by the big pharma to administer chemo.

  22. #22 Orac
    September 15, 2009

    Do tell, Judith.

    Perhaps you can give us some details. Which cancers? What was the extent of disease? How were they diagnosed? Did they have surgery or other conventional therapy as well?

    Inquiring minds want to know.

  23. #23 MikeMa
    September 15, 2009

    Judith is likely FOS. Cured is rarely a word used with cancer at any stage.

    Greed, on the other hand, I’d freely associate with woo-meisters who dole out fairy tales for money when science would return more.

  24. #24 DebinOz
    September 15, 2009

    At this moment, my children’s paternal grandmother is dying of pancreatic cancer at the age of 70. She is about ready to leave the hospital after her last and fruitless attempt with chemotherapy, to go home with hospice care for the duration.

    No alternative therapies were attempted, unless one counts fundamentalist christian prayer meetings and such. All appropriate medical interventions were applied (probably more so than if I were in charge; I thought personally that she had more chemo than she needed).

    I can’t gloat about the inefficacy of prayer, because my children will now lose their first grandparent.

    Life and death can be a crap-shoot; and I detest the alternative medical business taking advantage of people.

  25. #25 MikeMa
    September 15, 2009

    DebinOz
    Sorry for the loss of your children’s grandmother. At least the religious woo is free.

  26. #26 Calli Arcale
    September 15, 2009

    Prometheus:

    What is a “metabolizer diet”? “Non-metabolizer” would be nice euphemism for “dead”.

    In some of the later, live variants of the Dead Parrot sketch, a metabolism joke is included in the ridiculously long list of death euphemisms.

    “His metabolic processes are extinct!”

  27. #27 trrll
    September 15, 2009

    Keep believing those doctors to tell you what I presume want you want to hear… “I can cure your cancer.” The Dr’s make more money from you when you have cancer. They love it and when you walk in with cancer they see a new house or a new Mercedes. 60-70% of cancer patients eventually die from the chemo and results. Look at the statistical results of chemo which are probably skewed to make it look even better for them.

    They talk about the greed of Wall Street…how about the greed of doctors that are paid by the big pharma to administer chemo.

    And yet…cancer strikes everybody, even cancer doctors. If they weren’t taking their own medicine, you can be sure that somebody would have noticed. I’ve known a number of oncologists who had cancer, or who had children with cancer. And they received the very same treatments that oncologists recommend to their “regular” patients.

  28. #28 Calli Arcale
    September 15, 2009

    I can think of one exception, of a doctor who didn’t take the treatments he’d recommended. But it was very much a personal decision, and had nothing to do with thinking they weren’t effective. My grandfather died recently, and he believed he had pancreatic cancer. He was a general surgeon, and a brilliant man; he was also in his 90s, and felt strongly that he’d lived a complete life. When he experienced symptoms consistent with advanced pancreatic cancer, he simply didn’t feel there was any point getting it diagnosed. The most they could do is delay his death a bit, and he did not feel there was anything to be gained by that. He called in hospice care instead. We’ll never know if that’s what really killed him, but it seems likely that if it wasn’t pancreatic cancer, it was *some* kind of cancer. (Actually, he was rallying a bit, making that theory a bit more unlikely, when he had a nasty fall while getting the mail in December, and wound up with hypothermia. He went back into hospice care after that, and died a month later, having consciously chosen to refuse all foods, drinking only liquid morphine and the highballs he loved so much.)

    But that’s a different situation. He knew full well that conventional medicine could extend his life. That was precisely why he chose not to use it. He felt it was time to go.

    I’ve never met any other doctor who would refuse standard medical care for cancer, though I have met many who would refuse heroic medicine for terminal patients, and who try to talk their patients out of it. That’s more a matter of understanding just how uncomfortable it is to be intubated, and just how low the odds of recovery are in certain circumstances.

  29. #29 Interesting...
    September 15, 2009

    I don’t know if it’s been linked above or not, but Dr. Gonzalez has posted a “rebuttal” to the Journal of Clinical Oncology article on his website.

    The text:

    Recently, to our astonishment we learned that the Journal of Clinical Oncology, considered to be one of the pre-eminent oncology journals in the country, published an article about our NCI-NIH clinical study which claimed that chemotherapy worked better than our treatment with patients diagnosed with inoperable pancreatic cancer.

    Though I originally earned the grant from the NCI in 1998, though I was an investigator on this study throughout its existence, and though the clinical trial was set up to compare the efficacy of my treatment with chemotherapy, no one involved with the publication – not the Principal Investigator, Dr. John Chabot of Columbia Presbyterian Medical Center, nor any of his associates, informed me of their intent to publish this article, nor had I seen it. I learned of it serendipitously when the online version appeared on PubMed.

    I believe the article to be fraudulent in many regards, seeking to discredit me and salvage the reputations of those involved in supervising the study in the face of devastating findings of mismanagement on their part determined after official government investigations instigated at my request. In their official determination letter appearing on their website after a two-year investigation, the Office of Human Research Protections, the NIH agency in charge of investigating mismanagement on government funded studies, found that Dr. Chabot, who was in charge of admissions of patients, had improperly approved 42 out of a total of 62 patients, including 40 for whom he had failed to obtain appropriate written informed consent. Furthermore, the determination letter states that the Principal Investigator (Dr. Chabot) admitted he committed the managerial lapses, and in their letter the OHRP requires Columbia set up a program for training in appropriate research methodology – a serious indictment of a major academic medical center.

    To my astonishment, the JCO article nowhere mentions the findings of the OHRP, as if this lengthy investigation never existed, leaving the reader with the impression this study was properly managed by Dr. Chabot. In that regard, the article is a gross misrepresentation of what actually transpired during the study’s sad eight year history.

    More recently, Congressman Dan Burton of Indiana and I have requested that the Inspector General of the Department of Health and Human Services begin an investigation to determine if the supervisors of the study committed fraud in the mishandling of the project and its data. We have learned, for example, that according to the published medical literature, Dr. Chabot, who as Principal Investigator should have been a completely neutral manager with no ties to either treatment being evaluated, had worked closely with his Columbia colleague developing the very GTX chemotherapy regimen used against us in the study – an obvious conflict of interest that had never been declared to us. We believe Dr. Chabot believed it was in his best interest to discredit our alternative therapy and instead prove the value of a treatment he helped develop.

    Ironically, with no knowledge of the pending JCO article, I had only recently completed a lengthy book detailing the problems with the study and the gross mismanagement committed by the so-called conventional academic researchers assigned to run the project, and the attempts of myself and my colleague Dr. Isaacs to abide by the tenets of appropriate scientific investigation. It makes a good story of deceit, collusion, and disregard for patient safety that reaches right into the highest levels of the academic medical community

    Below I include a number of documents, several extracted from the book itself, that summarize the study’s history, and its various well-documented problems.

    He also includes some links to “supporting documents” below this text.

  30. #30 Wholly Father
    September 15, 2009

    Wow,

    The deafening silence has ended! Things are about to get very interesting.

  31. #31 trrll
    September 15, 2009

    It becomes clear from Gonzalez’s rebuttal how he can claim, and perhaps even deceive himself into believing, that his treatment is effective. His treatment is so complex and difficult that hardly any patients are actually “suitable.” For example, he requires that they have a sufficiently good “appetite” (and these are patients with pancreatic cancer). Indeed, it is clear that only a patient whose disease is progressing unusually slowly is capable of keeping with the regimen. As patients become sicker, and unable to maintain the regimen, he attributes their failure to survive as due to their failure to maintain the regimen, when it is actually the other way around. Only a patient with an unusually slowly progressing cancer–a “Patrick Swayze”–is actually capable of maintaining the regimen. And then Gonzalez take the credit for their survival.

    I have a great idea for a novel cancer therapy. The therapy will be a five mile run every day for three years. After all, running is healthy! Cancer is just a disease of indolence. I predict with great confidence that those patients who keep with the therapy will show much better survival than the average patient who accepts those horrible chemotherapy poisons.

  32. #32 Pablo
    September 15, 2009

    “Cessation of metabolic function prevented a large number of participants from continuing in the program, and they were excluded from the study.”

  33. #33 Andrew
    September 16, 2009

    The trial, as it has been reported, concludes that the Gonzalez protocol is a failure. The trial was not necessary to conclude that chemotherapy for this type of cancer is also a failure. With that in mind why not trial other alternate therapies. There must be something out there that works.

  34. #34 T
    September 16, 2009

    @ Andrew #33: The trial, as it has been reported, concludes that the Gonzalez protocol is a failure. The trial was not necessary to conclude that chemotherapy for this type of cancer is also a failure.

    You use “failure” twice for two separate events. If you think it’s a “failure” when a 100% cure rate isn’t achieved, then all medicine is a failure. Pancreatic cancer, as has been explained, is one of the single most difficult cancer diagnoses to treat. That nothing has been successful “curing” it is no surprise. It’s been demonstrated that current front-line evidence-based medical therapies can extend one’s post-diagnosis lifespan. That’s not a complete failure, and can reasonably be called a success based on the expectations of a pancreatic cancer diagnosis.

    What was demonstrated was that the Gonzalez protocol fails to live up to its claims of greater success than chemotherapy; in fact, failing to get close to the effects of chemo. That’s a much bigger failure.

    With that in mind why not trial other alternate therapies. There must be something out there that works.
    It’s not necessarily true that there will ever be something “that works” depending on your definition of treatment success.

    Wherever you set your bar, though, the greatest likelihood of achieving treatment success lies in building upon evidence-based foundations. Alternative therapies are often claimed to have phenomenal and frankly unrealistic success rates and generally lack any supporting evidence beyond unreliable anecdotes. To justify expensive medical trials with patients not taking the best known medical therapies there needs to be a true foundation of evidence and plausibility.

  35. #35 Scott
    September 16, 2009

    The trial, as it has been reported, concludes that the Gonzalez protocol is a failure.

    Correct.

    The trial was not necessary to conclude that chemotherapy for this type of cancer is also a failure.

    Entirely incorrect – extending life and easing suffering is most definitively NOT failure. It’s not complete success, but is still a major accomplishment, entirely owed to science.

    With that in mind why not trial other alternate therapies.

    Because there’s zero reason to believe they might work, they divert resources from research that has the potential to actually provide useful treatments, AND it’s grossly unethical to do human experimentation on “therapies” that don’t have a solid scientific foundation.

    There must be something out there that works.

    Pure wishful thinking. There doesn’t necessarily have to be any such thing.

  36. #36 oderb
    September 16, 2009

    The conflict of interest of Dr Chabot is more than enough to discredit the entire study. If there’s anyone who reads this site who has the slightest open mind about Gonzalez then read the detailed rebuttal on his website linked in comment 29. It’s quite compelling – of course I’m biased as I’ve been a patient of Dr Gonzalez for almost 20 years, and find him to be extraordinarily dedicated, knowledgeable, caring and most importantly effective.

  37. #37 Chris
    September 16, 2009

    oderb, you’ve been asked some questions. Perhaps you should consider answering them if you wish to be taken seriously.

  38. #38 trrll
    September 17, 2009

    The conflict of interest of Dr Chabot is more than enough to discredit the entire study.

    One of the hallmarks of the crank is the inevitable insistence that any “flaw” completely discredits a study whose results they find awkward. Even if we suppose that Dr Chabot had some kind of conflict of interest (when in fact Dr Gonzalez probably had a greater conflict of interest, considering that his lucrative practice rests upon belief in his protocol), how, specifically, is Dr. Chabot’s supposed conflict of interest responsible for the disastrous outcome in patients treated with the Gonzalez protocol, some of whom were clearly treated by Dr. Gonzalez (who complains bitterly about late payments for his services) himself? Are we to believe that Dr. Chabot crept into their rooms at night and murdered them? Are they still alive and doing well and being hidden by Dr. Chabot? If Dr. Gonzalez’s treatment really works, then where are his surviving patients?

  39. #39 trey
    September 18, 2009

    why can’t any other alternative treatments come into the U.S. Why do the big pharm. companies have compleat control over all drugs that the fda tests. how many jobs would be lost if they did find a good cure for cancer that didn’t cost 4,ooo per iv. I don’t think the doctors are to blame. No more than a cook who makes a read bake cake,knows about the proscess of making the mix.

    Chemo does kill more people than cancer. so why cant we choose other treatments for ourselves. Choose for ourselves. Now thats something we havent done in a long time.

  40. #40 trey
    September 18, 2009

    Why cant i find any info on Daniel Hauser that is of this week. I wonder why I cant find out how he is doing.

    I cant believe tht we have allowed the government to get so out of controle that they can tell us that they know whats best for our children. They orderd Daniel’s parents to make him take Chemo. We don’t live in a free country anymore. It doesn’t matter what was the best thing in someone elses mind. Thats his parents. Patric Schwazy made his own choices. He chose the path that they told him was best. He chose to believe it. Why can’t we have our own choices.

    My wife recovered from (what the doctors called ) stage four breast cancer. They didn’t give her much hope. When the insurance dropped her, they didn’t even give her a phone call.All help ended on the spot.Just a dollor not a name.
    We chose a path that is not allowed in the us. It has cost under $1000.00. We just got word that the cancer is gone.Just this week. I cant chose a path for another person. I believe God helped us on this one. 100%

  41. #41 Chris
    September 18, 2009

    trey, please read: Daniel Hauser Continues to Do Well (it was from last Saturday, since he is doing well I assume there will be no daily updates)

    Please also read: Understanding alternative medicine “testimonials” for cancer cures

    Also, what alternative cancer cures do you want to come to the US? What documentation do you have that they work? Why would we want to encourage people to do treatments that do not work, and may actually cause harm? For example, during a clinical test in the 1970s it was found that laetrile caused the patients to have symptoms of cyanide poisoning, and the cancers were not affected, and some “black salves” have been known to destroy perfectly good tissue — and again, not do anything for the cancer.

  42. #42 alison
    September 19, 2009

    Thanks, Orac, this is excellent. I’m going to use the info you’ve provided here in a critical thinking class tomorrow :-)

  43. #43 Neuroskeptic
    September 19, 2009

    Ridiculous treatment that obviously can’t work in “fails to work” shocker. Paper published. Believers in ridiculous treatment continue to believe.

    I don’t think these trials should be conducted. There’s a 5% chance that a treatment will perform better than placebo at p=0.05 and that only has to happen once for the whole alt. med world to throw a field day. Whereas the other 95% of the time when it doesn’t work they ignore it. Who benefits?

  44. #44 E.
    September 21, 2009

    Sadly, none of the comments or analysis on this paper are accurate because Dr.Chabot’s paper is bogus. How can you trust the outcomes of a ‘scientist’ who fails to comply with the law and gain written informed consent for his patients, (OHRP found him at fault with 2/3rds of the patients in the trial) and who fails to disclose this is his paper.

    You are all so ready to attack the ‘alternative guy’ and his protocol and yet you refuse to step back and question the misdeeds of Dr. Chabot. How are any of you helping cancer patients? Where would the world be today with out the greats of Lister and Marshall? Their views were ‘alternative’ after all but proved to be accurate.

    And please define ridiculous – nutrition to support the body’s own healing mechanisms or the use of a highly toxic chemotherapy drug or combination of drugs that kills both cancer cells and other healthy tissue as well…and in some cases can result in new cancers being created. The reality is there is a role for both and both deserve a fair and appropriate analysis. Chabot’s management of this trial was criminal and has put the world a decade behind on getting answers that pancreatic cancer patients truly need.

  45. #45 Orac
    September 21, 2009

    Oh, please, give me a break. I did criticize Chabot.

    Also, the difference in survival between the two groups was so enormous that, given that they were matched reasonably well, it’s highly unlikely that the design or administration of the study was enough to account for such a spectacularly bad result for Gonzalez. His patients, in essence, survived not detectably longer than patients with untreated pancreatic cancer, which is about the result I would have expected because they were patients with untreated pancreatic cancer given that the Gonzalez protocol is quackery.

  46. #46 fooker
    September 23, 2009

    All cancers are cured by restoring PH balance, taking superfoods, a lot more oxygen, adequate exercise and sunlight. Cancer cannot survive in an alkaline, oxygen lacking environment. Around 90% of cancer victims have cured themselves by following these ways reasonably well.

  47. #47 Chris
    September 23, 2009

    fooker, you made that all up, didn’t you? Well, if you didn’t you should able to provide evidence for your claim.

  48. #48 oderb
    September 30, 2009

    To Chris; # 37

    I chose to wait to respond to Chris and others until after my semi annual appointment with Dr Gonzalez earlier this week. (my comment is above at #36)

    How exactly does the nature of my cancer and its treatment by Gonzalez affect whether my comments should be taken seriously? I have learned from reading blogs such as this – over and over again – that the plural of anecdote is not data, so saying I had metastatic cancer and am alive 21 years later since I first saw Dr. Gonzalez is utterly irrelevant to my comments about his protocol – or that’s what you and others would say were I to make the case for Gonzalez based on the efficacy of his treatment for me.

    What I can say is that few patients have been with him longer. I have spent over 40 hours with him and find him to be honest, compassionate, incredibly knowledgeable and very patient in explaining the rationale for all aspects of his program. I believe him 100% when he says in his rebuttal and said to me personally earlier this week that only a small handful of patients sent to him were ones he thought were suitable and able to do his program. He also showed me a chart from the 2006 article that was attempted to be published by Dr. Chabot in JAMA (which he discusses in his rebuttal at dr-gonzalez. com) behind Dr. Gonzalez’ back, that showed that the longest lasting survivors were Gonzalez patients, not chemo patients, the opposite of the chart in JCO!! He said flatly – not that his patients lived longer on average – how could they when many died before or just after they first saw him but that the longest surviving patients were his.

    I don’t expect anyone here to still have an open mind about his work after the JCO study – in part because few if any of you had an open mind to begin with – but if the fraud investigation is carried out fairly and thoroughly and after publication of Dr. Gonzalez book on the study I am very sure that most open minded people will conclude the study was so riddled with biases intentional or not, that no conclusion about the Gonzalez protocol efficacy can be made as a result of the JCO article, and that his work still deserves further investigation.

    And as far as the scientific plausibility of his protocol, if you listen to the tapes of his all day talk in London a few months ago – available at New Spring Press, he talks at great length of the science behind his approach to cancer, and the convergence of recent discoveries of the importance of cancer stem cells to the ‘germ’ cells and trophoblasts discovered by Dr Beard 100 years ago. To simply say that cancer is a genetic disease and therefore enzymes have no possibility of working is illogical.

    Finally regarding plausibility if his work is so utterly implausible how then can one explain the study where mice were given the Gonzalez pancreatic enzymes and had significantly less cancer than the controls without concluding that further research on his enzymes was warranted. This research was peer reviewed and published in the major journal Pancreas.

    See http://www.dr-gonzalez.com/mice04.htm

    In retrospect I believe that funding animal and molecular research on his program before the current trail as suggested by some would have been useful and maybe led to a more unbiased human trial. In the meantime stay tuned for more in the months ahead when the book and the fraud investigation come to light.

  49. #49 Joseph
    September 30, 2009

    @oderb: You apparently claim to be open minded. (That’s usually a canard used by cranks, but that’s neither here nor there.) Let me ask you this. Are you open minded about the distinct possibility that Dr. Gonzales’ protocol just doesn’t work?

  50. #50 oderb
    October 9, 2009

    Joseph,

    I wouldn’t have strongly advocated further trials or other means of weighing the efficacy of Gonzalez work If I wasn’t open minded. I would have simply said that his method works and all the criticism is misplaced, so yes I am open minded. I have invested much time, money and effort in complying with his program and If I believed that the study was valid I would stop following his program today.

    The bottom line is who do you believe – the study author, who has been discredited for severe protocol violations – or Gonzalez who says only a handful of the patients he treated were able or willing to follow the protocol. Knowing Gonzalez well I believe in his integrity and so am willing to give him the benefit of the doubt – at least for now.

  51. #51 titmouse
    October 9, 2009

    oderb, even honest doctors can be mistaken.

  52. #52 Scott
    October 9, 2009

    oderb,

    You completely miss the point. Hugely so. Gonzalez’s integrity or lack thereof has absolutely nothing to do with anything. The fundamental question is, does his protocol work? And the answer is quite definitively NO. None of the criticisms of the study are anywhere near enough to account for the massive difference in survivability.

    You’re wasting your time and money on something that is not helping you one whit.

  53. #53 Carolyn
    October 9, 2009

    I’m neither for or against the coffee enema, but I do know that almost everyone dies from pancreatic cancer. I know that chemo causes tumors elsewhere in the body as well as you are sick as a dog and loss of hair so I don’t understand why all of you are rushing over to the chemo side either. You all sound a little crazy to me.

  54. #54 oderb
    October 16, 2009

    Scott,

    His integrity is exactly the point – which you miss. I believe him when he says that only a handful of the patients sent to him complied with the program, and that’s why they died before the chemo patients. They essentially had no treatment. I also believe him when he shows me a chart that indicates several of his patients lived longer than the longest lasting chemo survivor. So it comes down to who you believe. If the investigations are fairly carried out Gonzalez will be vindicated.

    If anyone is still interested I understand Gonzalez will be Larry King Monday night along with a conventional doctor or two – needless to say it will be a lively discussion.

  55. #55 Ramel
    October 16, 2009

    Hmmm, is this the alt med equivalent of Stockholm syndrome?

  56. #56 Chris
    October 17, 2009

    oderb:

    I also believe him when he shows me a chart that indicates several of his patients lived longer than the longest lasting chemo survivor.

    My, you are gullible. Aren’t you?

    Why were the survivors not part of the study this post is about?

  57. #57 titmouse
    October 17, 2009

    oderb,

    You argue that the patients who requested the Gonzalez protocol couldn’t do it and so they died.

    Consider the other possibility: dead men take no enemas –i.e., the Gonzalez patients died and so they could not do the protocol.

    Look at the study results graph. Note that about half of the Gonzalez patients are dead by about month 4. Contrast that with the chemo arm, where nearly all patients are still alive.

  58. #58 Chris Foley MD
    May 6, 2010

    Just found this. although your vitriol is certainly your right, your understanding of the concepts behind the study is really pathetic. If you do not understand the principles of detoxification (and you clearly do not) nor the mechanism whereby dig enzymes might be of value, then you should just move on, report the findings, and otherwise keep your inaccurate editorial tongue to yourself. It adds little.

  59. #59 Sandra D.
    June 18, 2010

    In February I was diagnosed with stage IV colon cancer (it is in my liver). I refused all conventional recommended treatments (surgery, radiation, chemo).

    Dr. Gonzalez would not take me as a patient because, based on my medical records, he believed I was destined for a colon blockage. I then contacted a nutritionist who worked many years with Dr. Kelley and he is coaching me on the Kelley/Gonzalez protocols.

    It has been more than four months. Yes, the protocols are tedious, but I have no doubt that I am healing. I am working full-time. I feel good. I am not turning yellow from liver failure. My liver enzyme tests are normal (as is everything else except cholesterol). Since my life expectancy at diagnosis was 6-12 months, I should be pretty sick by now. I am not. I will contact you again in 3 or 4 months an let you know how my colonoscopy and ultrasound went.

    Gonzalez treats many physicians (including oncologists) and their relatives. That is saying a lot.

    Is the AMA paying you rabid anti-alternative health care bloggers to blog? For shame.

  60. #60 Chris
    June 18, 2010

    Chris Foley, MD: was your medical training from an online college? Because it is obvious you missed out on basic biochemistry and the function of the liver.

    Sandra D., you have a nice anecdote. It is hard to believe. Perhaps you are being paid by Kelley. Oh, the shill gambit can go both ways.

  61. #61 RF
    July 9, 2010

    In fairness to Gonzalez,

    if the published study had no actual control arm

    and

    the paper was initially rejected for publication

    and

    the raw survival data has been improperly manipulated, the study may be completely worthless.

    Am I correct that there was no control group? If there was no control, (Jesus Christ!) and the raw SURVIVAL data has been manipulated (double Jesus Christ!), should we be jumping to a whole lot of conclusions about Gonzalez’s treatment.

    I’ve got an idea for an experiment: Try getting a paper about an experiment published in a peer reviewed journal that has no control and tell me how your results.

    Gonzalez’s treatment may be of no use, but are we sure that the study proved ANYTHING if the data has been improperly tinkered with.

    –RJ

  62. #62 Someone who read the paper
    July 9, 2010

    RF/RJ,

    There was a control arm: those receiving standard chemotherapy for the given diagnosis. A “placebo” arm would not be ethically appropriate as it would withold treatments known to have at least some success in relevant medical outcomes. The use of standard-treatment controls is common and perfectly acceptable.

    Papers are initally rejected all the time. This can be for any number of reasons: doesn’t fit the editor’s vision of a journal’s content, not sufficiently “impactful” for a given publication (esp. those with high impact factor scores), flaws in conclusions or methodologies were too substantial, requested revisions may have demanded too much (e.g., additional experiments that couldn’t be performed)…it’s a safe bet that a large percentage of journal articles have been submitted to more than one journal based on one or more of these issues. Being rejected for publication is not uncommon, nor is it a particularly shameful thing; in this case it was published in an appropriate peer-revied journal.

    Improper data manipulation is a serious charge. If this is actually the case, Gonzalez should take the calim to the journal editor directly, possibly publicly via a letter to the editor, to which the (other) authors will generally respond with a rebuttal or correction of some sort. Otherwise, it sounds like he’s blowing smoke and trying to salvage some of his now-tarnished reputation, dontchya think?

  63. #63 theresa
    July 9, 2010

    When you are told that you have a 1 in 10 chance of still being alive in 1 yr with chemotherapy for your stage 4 cancer…. WHY would you not look into something else? WHY would I be that stupid. The alternative therapy odds couldnt be any worse! As a doctor, how could you sit there and not give me other options? Your chemo or nothing else. I smoked, I ate crap, high stress job, 4 young children, deployed husband… dont you see other areas that could improve health besides just chemo. You know my immune system is shot, I am overall unhealthy, but the only suggestion I get is start chemo right away. I would think I was too unhealthy to endure chemo. I was, so I didnt. They said I was dying, but the only thing they can think of is to hook me up to chemo drugs. That is a very expensive travesty, and they should be sued. They said they could not cure me, but they would treat me… with poison and then nauseau drugs, pain pills, and antibiotics to help my side effects. what? needless to say, I didnt do chemo. I ate extremely well(very specific diet), exercised, massages, yoga, enjoyed my family, absolutely no pain medications or anything else. I am feeling great! It has been 14 mos, and all the sites of metastasis have either disappeared or greatly reduced in size. I am discussing some treatment options with my physician for possible surgery or radiation for one of the sites of metastasis. Yes, my physician did not recommend my choice of treatment to begin with, but continued to monitor me throughout and make treatment recommendations.

    Why do you insist on tearing down people with pancreatic or stage 4 lung cancer or a few other cancers that chemo does nothing for? We are dying. Why do we have to be tortured with poisons, pain, weakness, vomiting etc for the 4 months the patient tries to live through the chemo? Some cancers have better odds with chemo, others just dont! The body needs the peace.

  64. #64 Scott
    July 9, 2010

    When you are told that you have a 1 in 10 chance of still being alive in 1 yr with chemotherapy for your stage 4 cancer…. WHY would you not look into something else? WHY would I be that stupid. The alternative therapy odds couldnt be any worse!

    Actually, as this case showed, the alternative therapy odds most certainly can be worse. People died even faster under the Gonzalez protocol.

    As a doctor, how could you sit there and not give me other options? Your chemo or nothing else. I smoked, I ate crap, high stress job, 4 young children, deployed husband… dont you see other areas that could improve health besides just chemo. You know my immune system is shot, I am overall unhealthy, but the only suggestion I get is start chemo right away. I would think I was too unhealthy to endure chemo. I was, so I didnt. They said I was dying, but the only thing they can think of is to hook me up to chemo drugs. That is a very expensive travesty, and they should be sued. They said they could not cure me, but they would treat me… with poison and then nauseau drugs, pain pills, and antibiotics to help my side effects.

    They don’t offer anything else because there is nothing else to offer. Just because you don’t like the truth doesn’t make it false.

    what? needless to say, I didnt do chemo. I ate extremely well(very specific diet), exercised, massages, yoga, enjoyed my family, absolutely no pain medications or anything else. I am feeling great! It has been 14 mos, and all the sites of metastasis have either disappeared or greatly reduced in size. I am discussing some treatment options with my physician for possible surgery or radiation for one of the sites of metastasis. Yes, my physician did not recommend my choice of treatment to begin with, but continued to monitor me throughout and make treatment recommendations.

    So you were either lucky, the diagnosis was mistaken, or you’re not telling the truth. (No way to tell that online.) No evidence whatsoever than anything you listed had any effect whatsoever on anything.

    Why do you insist on tearing down people with pancreatic or stage 4 lung cancer or a few other cancers that chemo does nothing for? We are dying. Why do we have to be tortured with poisons, pain, weakness, vomiting etc for the 4 months the patient tries to live through the chemo? Some cancers have better odds with chemo, others just dont! The body needs the peace.

    It’s quite true that chemo doesn’t help odds with some cancers. And you know what? Doctors know that, and don’t recommend it for those cases!

    You seem to be laboring under the misconception that There Must Be An Answer. The real world doesn’t work that way. Sometimes crappy things happen to good people and there’s nothing effective that can be done about it.

  65. #65 triskelethecat
    July 9, 2010

    @ Scott: she could be telling the truth about her colon cancer. What I don’t believe is that the doctors gave her any certain length of time she had left to live.

    According to a colon cancer website:In general, approximately 8-15% of people with stage 4 colon cancer are still alive five years after their diagnosis. It does not say whether those persons underwent conventional treatment or not. So, even without treatment,she could be feeling fine still however long after her diagnosis (5 months or 14 months…her diagnosis time range has changed).

  66. #66 Scott
    July 9, 2010

    She certainly could be, yes. But we have no way to confirm, and there are people around who would make up such a story. So we can’t be sure.

    Also, theresa didn’t mention a type of cancer; the assumption of colon seems unjustified.

  67. #67 RJ
    July 9, 2010

    To Someone who read the paper:

    My comment about the lack of a control arm, and please correct me if I’m wrong, is based on the following suppositions:

    The use of Gemzar plus Taxotere and Xeloda (“GTX”) was being compared to the Gonzalez treatment.

    The problem is that GTX was an experimental treatment itself. An experimental treatment is as a rule not a control arm.

    I’m unsure what conclusions can be drawn from this study.

    –RJ

  68. #68 Someone who read the paper
    July 10, 2010

    The use of Gemzar plus Taxotere and Xeloda (“GTX”) was being compared to the Gonzalez treatment.

    The problem is that GTX was an experimental treatment itself. An experimental treatment is as a rule not a control arm.

    I’m unsure what conclusions can be drawn from this study

    Simplest valid conclusion: the Gonzalez regimen cannot hold a candle to the success of GTX chemotherapy. The difference was so huge that the study was stopped early because withholding a more successful treatment from patients was considered ethically improper. Isn’t that obvious?

    Also obvious: chemotherapy is a continually evolving treatment option. By 2002 the medical literature was already growing with data that suggested that Gemcitabine alone was not as efficacious as Gemcitabine combined with other chemotherapeutic agents, including Docetaxel & Capecitabine. It would not be ethically appropriate to withhold combination treatments that had plausible and demonstrated survival benefits to keep using a Gemcitabine-only control group for Gonzalez’s ego or whatever.

    You’ll also note in the manuscript that there are comparisons to population survival data from the SEER database. Even without the GTX arm, it would be valid to conclude that the Gonzalez regimen did worse than historical averages; it was clearly not as successful as the doctor has bragged about.

    The study has many flaws. (Not least of which was ever risking people’s lives investigating Gonzalez’s largely unbelievable claims about a dubious treatment.) It is, however, light years better than any other published data on the Gonzalez regimen and it is not improper to draw some basic conclusions: a treatment with low prior plausibility–despite great claims of success–performed so poorly compared to chemotherapy and historical survival data, and was associated with dismal quality of life data, that it was an ethical necessity to discontinue the treatment.

  69. #69 RJ
    July 11, 2010

    Can we agree that from a scientific standpoint that a control arm did NOT exist.

    You may disagree with Gonzalez or think his treatment is junk…however, from a scientific standpoint, not using a proper control may be considered a, uh, no-no?

    Imagine if you ran a different study and then in explaining to the editorial board of NEJM or JAMA that the reason you used an experimental treatment as a control, you used the following comment:

    “well, it’s obvious that chemotherapy is evolving so uh, we went ahead with a treatment that, well, you know might be experimental right now, but…”

    This is extraordinarily serious business involving people’s lives.

    If what happened is people thought that they were going to get either the experimental Gonzalez treatment or the current standard treatment, and then instead they got an experimental non-Gonzalez treatment, then I think that is worth noting.

    –RJ

  70. #70 W. Kevin Vicklund
    July 11, 2010

    Can we agree that from a scientific standpoint that a control arm did NOT exist.

    No, we can’t.

    If what happened is people thought that they were going to get either the experimental Gonzalez treatment or the current standard treatment, and then instead they got an experimental non-Gonzalez treatment, then I think that is worth noting.

    But that’s not what happened. The patients got either the experimental Gonzalez treatment, or the current standard treatment of gemcitabine (Gemzar), which was approved in 1996.

  71. #71 W. Kevin Vicklund
    July 11, 2010

    My apologies to RJ, I thought I had read all of the thread but I had missed his comment prior to the one to which I responded. I still stand by my first half of my comment, but my second half is invalid. I’m going to follow up with another comment, but I thought getting out my apology as quickly as I could was in order.

  72. #72 RJ
    July 11, 2010

    My understanding is that Gemzar alone was the standard treatment for pancreatic cancer (the cancer that was looked at in the study).

    I think the standard treatment would be considered a control arm. (and I think you may agree with that)

    GTX, which is a combination of drugs (ie Gemzar plus Taxotere and Xeloda) is a different treatment than Gemzar alone. (and I think a clinical oncologist may agree with that).

    If you think that GTX is identical to Gemzar alone, I disagree with you.

    –RJ

  73. #73 Someone who read the paper
    July 11, 2010

    I’m perfectly willing to agree that a gemcitabine-alone control would be cleaner from an experimental design standpoint. However, I’m sure you would agree that, since the 1998 approval of the initial study protocol, there have been relevant advances in chemotherapy. (The 2001 change in the protocol was due to the abject failure of any sort of proper randomization and the progress in chemo treatments.)

    What this study offers is two groups of fairly similar patients, one receiving a gemcitabine-based chemotherapy and the other receiving an experimental arm of proteolytic enzyme treatment. It’s perfectly valid to compare the outcomes of treatment 1 versus treatment 2, is it not? One treatment was clearly superior in objective measures of survival and quality of life, right? So much so that it might be unethical to continue to force patients to take the other treatment, don’t you think?

    We can also compare these two treatments against historical sruvival data–the SEER database–to provide a further perspective on the survival of the two treatment arms. Now we can compare treatment 1 and treatment 2 to the general historical outcomes.

    Since gemcitabine-based chemotherapy was (and still is) the best science-based treatment option, the control arm did get an appropriate treatment. Contrary to popular alt-med belief, treating physicians do tailor their pharmacotherapies to the individual patients. The control arm did not receive the same treatment across the board, though 19/23 did receive gemcitabine+capecitabine+docetaxel. This combination was “experimental” in the sense that it hadn’t yet been the subject of published clinical trials, but there is PubMed literature from ~2002 that suggests this was a reasonable next step given the success to-date with gemcitabine-based combo therapies in comparison to gemcitabine alone. The current literature is clear that the GTX combo seems to be a treatment of some promise. For a cancer with such a generally dismal prognosis, there is still much trial-and-error experimentation going on to find therpaeutic combinations that may provide benefit.

    I’d like to throw RJ a few further questions:

    *If gemcitabine had been given alone to the control group, we can’t say what the results of the control treatment would have been. For the sake of argument, lets say it was similar to the historical SEER numbers (which would probably underestimate its effect based on gemcitabine’s FDA approval following success in improving survival rates). None of that would change the results of the Gonzalez Regimen arm…would you still think there was nothing that could be concluded from this study?

    *What if there had been no chemo treatment arm at all? Would it have been a reasonable course of action to compare the regimen with historical survival data alone? If not, why? If so, what do the present results suggest?

    *Should this study have even been done given how implausible the treatment regimen is to begin with?

    *Given the present state of the published literature, would it be justified to study this regimen any further? Would it be justified for any physician to prescribe such a regimen over chemotherapy to any patient for which a gemicitabine-based therapy would be appropriate?

  74. #74 Someone who read the paper
    July 11, 2010

    I’m perfectly willing to agree that a gemcitabine-alone control would be cleaner from an experimental design standpoint. However, I’m sure you would agree that, since the 1998 approval of the initial study protocol, there have been relevant advances in chemotherapy. (The 2001 change in the protocol was due to the abject failure of any sort of proper randomization and the progress in chemo treatments.)

    What this study offers is two groups of fairly similar patients, one receiving a gemcitabine-based chemotherapy and the other receiving an experimental arm of proteolytic enzyme treatment. It’s perfectly valid to compare the outcomes of treatment 1 versus treatment 2, is it not? One treatment was clearly superior in objective measures of survival and quality of life, right? So much so that it might be unethical to continue to force patients to take the other treatment, don’t you think?

    We can also compare these two treatments against historical sruvival data–the SEER database–to provide a further perspective on the survival of the two treatment arms. Now we can compare treatment 1 and treatment 2 to the general historical outcomes.

    Since gemcitabine-based chemotherapy was (and still is) the best science-based treatment option, the control arm did get an appropriate treatment. Contrary to popular alt-med belief, treating physicians do tailor their pharmacotherapies to the individual patients. The control arm did not receive the same treatment across the board, though 19/23 did receive gemcitabine+capecitabine+docetaxel. This combination was “experimental” in the sense that it hadn’t yet been the subject of published clinical trials, but there is PubMed literature from ~2002 that suggests this was a reasonable next step given the success to-date with gemcitabine-based combo therapies in comparison to gemcitabine alone. The current literature is clear that the GTX combo seems to be a treatment of some promise. For a cancer with such a generally dismal prognosis, there is still much trial-and-error experimentation going on to find therpaeutic combinations that may provide benefit.

    I’d like to throw RJ a few further questions:

    *If gemcitabine had been given alone to the control group, we can’t say what the results of the control treatment would have been. For the sake of argument, lets say it was similar to the historical SEER numbers (which would probably underestimate its effect based on gemcitabine’s FDA approval following success in improving survival rates). None of that would change the results of the Gonzalez Regimen arm…would you still think there was nothing that could be concluded from this study?

    *What if there had been no chemo treatment arm at all? Would it have been a reasonable course of action to compare the regimen with historical survival data alone? If not, why? If so, what do the present results suggest?

    *Should this study have even been done given how implausible the treatment regimen is to begin with?

    *Given the present state of the published literature, would it be justified to study this regimen any further? Would it be justified for any physician to prescribe such a regimen over chemotherapy to any patient for which a gemicitabine-based therapy would be appropriate?

  75. #75 Someone who read the paper
    July 11, 2010

    I’m perfectly willing to agree that a gemcitabine-alone control would be cleaner from an experimental design standpoint. However, I’m sure you would agree that, since the 1998 approval of the initial study protocol, there have been relevant advances in chemotherapy. (The 2001 change in the protocol was due to the abject failure of any sort of proper randomization and the progress in chemo treatments.)

    What this study offers is two groups of fairly similar patients, one receiving a gemcitabine-based chemotherapy and the other receiving an experimental arm of proteolytic enzyme treatment. It’s perfectly valid to compare the outcomes of treatment 1 versus treatment 2, is it not? One treatment was clearly superior in objective measures of survival and quality of life, right? So much so that it might be unethical to continue to force patients to take the other treatment, don’t you think?

    We can also compare these two treatments against historical sruvival data–the SEER database–to provide a further perspective on the survival of the two treatment arms. Now we can compare treatment 1 and treatment 2 to the general historical outcomes.

    Since gemcitabine-based chemotherapy was (and still is) the best science-based treatment option, the control arm did get an appropriate treatment. Contrary to popular alt-med belief, treating physicians do tailor their pharmacotherapies to the individual patients. The control arm did not receive the same treatment across the board, though 19/23 did receive gemcitabine+capecitabine+docetaxel. This combination was “experimental” in the sense that it hadn’t yet been the subject of published clinical trials, but there is PubMed literature from ~2002 that suggests this was a reasonable next step given the success to-date with gemcitabine-based combo therapies in comparison to gemcitabine alone. The current literature is clear that the GTX combo seems to be a treatment of some promise. For a cancer with such a generally dismal prognosis, there is still much trial-and-error experimentation going on to find therpaeutic combinations that may provide benefit.

    I’d like to throw RJ a few further questions:

    *If gemcitabine had been given alone to the control group, we can’t say what the results of the control treatment would have been. For the sake of argument, lets say it was similar to the historical SEER numbers (which would probably underestimate its effect based on gemcitabine’s FDA approval following success in improving survival rates). None of that would change the results of the Gonzalez Regimen arm…would you still think there was nothing that could be concluded from this study?

    *What if there had been no chemo treatment arm at all? Would it have been a reasonable course of action to compare the regimen with historical survival data alone? If not, why? If so, what do the present results suggest?

    *Should this study have even been done given how implausible the treatment regimen is to begin with?

    *Given the present state of the published literature, would it be justified to study this regimen any further? Would it be justified for any physician to prescribe such a regimen over chemotherapy to any patient for which a gemicitabine-based therapy would be appropriate?

  76. #76 Someone who read the paper
    July 11, 2010

    I’m perfectly willing to agree that a gemcitabine-alone control would be cleaner from an experimental design standpoint. However, I’m sure you would agree that, since the 1998 approval of the initial study protocol, there have been relevant advances in chemotherapy. (The 2001 change in the protocol was due to the abject failure of any sort of proper randomization and the progress in chemo treatments.)

    What this study offers is two groups of fairly similar patients, one receiving a gemcitabine-based chemotherapy and the other receiving an experimental arm of proteolytic enzyme treatment. It’s perfectly valid to compare the outcomes of treatment 1 versus treatment 2, is it not? One treatment was clearly superior in objective measures of survival and quality of life, right? So much so that it might be unethical to continue to force patients to take the other treatment, don’t you think?

    We can also compare these two treatments against historical sruvival data–the SEER database–to provide a further perspective on the survival of the two treatment arms. Now we can compare treatment 1 and treatment 2 to the general historical outcomes.

    Since gemcitabine-based chemotherapy was (and still is) the best science-based treatment option, the control arm did get an appropriate treatment. Contrary to popular alt-med belief, treating physicians do tailor their pharmacotherapies to the individual patients. The control arm did not receive the same treatment across the board, though 19/23 did receive gemcitabine+capecitabine+docetaxel. This combination was “experimental” in the sense that it hadn’t yet been the subject of published clinical trials, but there is PubMed literature from ~2002 that suggests this was a reasonable next step given the success to-date with gemcitabine-based combo therapies in comparison to gemcitabine alone. The current literature is clear that the GTX combo seems to be a treatment of some promise. For a cancer with such a generally dismal prognosis, there is still much trial-and-error experimentation going on to find therpaeutic combinations that may provide benefit.

    I’d like to throw RJ a few further questions:

    *If gemcitabine had been given alone to the control group, we can’t say what the results of the control treatment would have been. For the sake of argument, lets say it was similar to the historical SEER numbers (which would probably underestimate its effect based on gemcitabine’s FDA approval following success in improving survival rates). None of that would change the results of the Gonzalez Regimen arm…would you still think there was nothing that could be concluded from this study?

    *What if there had been no chemo treatment arm at all? Would it have been a reasonable course of action to compare the regimen with historical survival data alone? If not, why? If so, what do the present results suggest?

    *Should this study have even been done given how implausible the treatment regimen is to begin with?

    *Given the present state of the published literature, would it be justified to study this regimen any further? Would it be justified for any physician to prescribe such a regimen over chemotherapy to any patient for which a gemicitabine-based therapy would be appropriate?

  77. #77 Someone who read the paper
    July 11, 2010

    I’m perfectly willing to agree that a gemcitabine-alone control would be cleaner from an experimental design standpoint. However, I’m sure you would agree that, since the 1998 approval of the initial study protocol, there have been relevant advances in chemotherapy. (The 2001 change in the protocol was due to the abject failure of any sort of proper randomization and the progress in chemo treatments.)

    What this study offers is two groups of fairly similar patients, one receiving a gemcitabine-based chemotherapy and the other receiving an experimental arm of proteolytic enzyme treatment. It’s perfectly valid to compare the outcomes of treatment 1 versus treatment 2, is it not? One treatment was clearly superior in objective measures of survival and quality of life, right? So much so that it might be unethical to continue to force patients to take the other treatment, don’t you think?

    We can also compare these two treatments against historical sruvival data–the SEER database–to provide a further perspective on the survival of the two treatment arms. Now we can compare treatment 1 and treatment 2 to the general historical outcomes.

    Since gemcitabine-based chemotherapy was (and still is) the best science-based treatment option, the control arm did get an appropriate treatment. Contrary to popular alt-med belief, treating physicians do tailor their pharmacotherapies to the individual patients. The control arm did not receive the same treatment across the board, though 19/23 did receive gemcitabine+capecitabine+docetaxel. This combination was “experimental” in the sense that it hadn’t yet been the subject of published clinical trials, but there is PubMed literature from ~2002 that suggests this was a reasonable next step given the success to-date with gemcitabine-based combo therapies in comparison to gemcitabine alone. The current literature is clear that the GTX combo seems to be a treatment of some promise. For a cancer with such a generally dismal prognosis, there is still much trial-and-error experimentation going on to find therpaeutic combinations that may provide benefit.

    I’d like to throw RJ a few further questions:

    *If gemcitabine had been given alone to the control group, we can’t say what the results of the control treatment would have been. For the sake of argument, lets say it was similar to the historical SEER numbers (which would probably underestimate its effect based on gemcitabine’s FDA approval following success in improving survival rates). None of that would change the results of the Gonzalez Regimen arm…would you still think there was nothing that could be concluded from this study?

    *What if there had been no chemo treatment arm at all? Would it have been a reasonable course of action to compare the regimen with historical survival data alone? If not, why? If so, what do the present results suggest?

    *Should this study have even been done given how implausible the treatment regimen is to begin with?

    *Given the present state of the published literature, would it be justified to study this regimen any further? Would it be justified for any physician to prescribe such a regimen over chemotherapy to any patient for which a gemicitabine-based therapy would be appropriate?

  78. #78 Someone who read the paper
    July 11, 2010

    I’m perfectly willing to agree that a gemcitabine-alone control would be cleaner from an experimental design standpoint. However, I’m sure you would agree that, since the 1998 approval of the initial study protocol, there have been relevant advances in chemotherapy. (The 2001 change in the protocol was due to the abject failure of any sort of proper randomization and the progress in chemo treatments.)

    What this study offers is two groups of fairly similar patients, one receiving a gemcitabine-based chemotherapy and the other receiving an experimental arm of proteolytic enzyme treatment. It’s perfectly valid to compare the outcomes of treatment 1 versus treatment 2, is it not? One treatment was clearly superior in objective measures of survival and quality of life, right? So much so that it might be unethical to continue to force patients to take the other treatment, don’t you think?

    We can also compare these two treatments against historical sruvival data–the SEER database–to provide a further perspective on the survival of the two treatment arms. Now we can compare treatment 1 and treatment 2 to the general historical outcomes.

    Since gemcitabine-based chemotherapy was (and still is) the best science-based treatment option, the control arm did get an appropriate treatment. Contrary to popular alt-med belief, treating physicians do tailor their pharmacotherapies to the individual patients. The control arm did not receive the same treatment across the board, though 19/23 did receive gemcitabine+capecitabine+docetaxel. This combination was “experimental” in the sense that it hadn’t yet been the subject of published clinical trials, but there is PubMed literature from ~2002 that suggests this was a reasonable next step given the success to-date with gemcitabine-based combo therapies in comparison to gemcitabine alone. The current literature is clear that the GTX combo seems to be a treatment of some promise. For a cancer with such a generally dismal prognosis, there is still much trial-and-error experimentation going on to find therpaeutic combinations that may provide benefit.

    I’d like to throw RJ a few further questions:

    *If gemcitabine had been given alone to the control group, we can’t say what the results of the control treatment would have been. For the sake of argument, lets say it was similar to the historical SEER numbers (which would probably underestimate its effect based on gemcitabine’s FDA approval following success in improving survival rates). None of that would change the results of the Gonzalez Regimen arm…would you still think there was nothing that could be concluded from this study?

    *What if there had been no chemo treatment arm at all? Would it have been a reasonable course of action to compare the regimen with historical survival data alone? If not, why? If so, what do the present results suggest?

    *Should this study have even been done given how implausible the treatment regimen is to begin with?

    *Given the present state of the published literature, would it be justified to study this regimen any further? Would it be justified for any physician to prescribe such a regimen over chemotherapy to any patient for which a gemicitabine-based therapy would be appropriate?

  79. #79 UBS
    July 18, 2010

    Mark Levine’s article was published at the JCO’s website (JCO = Jornal of Clinical Oncology = the same journal that published the Chabot et al article).

    Chabot et al should be congratulated on their persistence and determination to compare pancreatic enzymes versus chemotherapy. Can it be concluded that their study proves that enzyme therapy is markedly inferior? On the basis of the study design, my answer is no. It is not possible to make a silk purse out of a sow’s ear. Given the scarcity of resources for cancer research, there are many more important questions to address.

    (UBS note: I omitted a footnote indicator from the quote above)

    Levine also gives an interesting discussion in the same article:

    Is the study design valid? I would like to focus the discussion on the validity of the use of a controlled observational design to establish efficacy in the Chabot et al study. Although 55 patients were enrolled onto the cohort study, nine more enzyme-treated patients than chemotherapy patients were analyzed. This imbalance is troubling. Fifteen patients were excluded, but one wonders whether they received treatment and were excluded after the analysis was performed. If this occurred, it could lead to bias. Second, in any observational study, there is the possibility of an imbalance in baseline prognostic factors between intervention groups that could confound analysis and potentially lead to bias. There was no statistically significant difference detected in baseline characteristics for many factors except total bilirubin and albumin. One wonders whether there were more liver metastases in the enzyme-treated group than in the chemotherapy group, but this information is not provided. The authors used multivariate analysis and propensity score adjustment to attempt to control for any potential imbalance in baseline characteristics; however, such adjustment does not correct for potential unknown confounders.

    (UBS note: I also omitted a footnote indicator from the above; please also note that fonts used may differ (from above) in the original source material.)

    Levine’s editorial is posted (it’s free) at the JCO website:

    http://jco.ascopubs.org/cgi/content/full/28/12/1979

    —UBS (ie Unconvinced by Study )

  80. #80 titmouse
    July 18, 2010

    Blah blah blah “control group”…

    Look, doesn’t matter what the non-Gonzalez group got. For the sake of argument, let’s say they all got friggin’ Fred Flintstone’s multivitamins.

    The point is, the take-home message is:

    THE GONZALEZ REGIMEN IS POOP!

  81. #81 Lewriter
    July 20, 2010

    To Someone who read the paper:

    I looked at Mark Levine’s article at the JCO’s site.

    Did you?

    The live metastasis comment makes sense. So does the excluded patients comment.

    Any ideas?

  82. #82 lewriter
    July 22, 2010

    Sorry for the mistake above. I should have said “liver metastases”.

  83. #83 Someone who read the paper
    July 22, 2010

    Levine’s editorial read:

    Fifteen patients were excluded, but one wonders whether they received treatment and were excluded after the analysis was performed. If this occurred, it could lead to bias.

    Chabot et al. stated the exclusion criteria in the paper and explained the excluded patients thusly:

    Of 70 patients with pancreatic cancer who expressed interest in the study, 15 patients were excluded (Fig 1); nine did not meet the trial inclusion criteria; and one additional patient signed a consent form that was misplaced because of a change in staffing. Five additional patients had a delay in enrollment of greater than 8 weeks from the date of diagnosis and, thus, were ineligible.

    My interpretation of this is that the 15 excluded patients are 9 that didn’t meet the defined criteria + 1 with a lost consent form + 6 that didn’t start the treatment within the predetermined window = 15 total exclusions. I think the language used by Chabot et al. is muddled, so I cannot be certain this is 100% correct. Levine was clearly confused.

    Of this, I will make one note: it is possible that the 6 patients excluded due to the enrollment criteria of enrollment with a “signed[,] witnessed and dated consent form within 8 weeks of diagnosis” was a post-hoc exclusion criteria. If so, this could be a major ethical violation if it excluded treated patients that had some biased outcome. However, there’s no present indication that these patients ever received treatment, and the paper states that only 55 patients received an intervention. Levine’s question would possibly have been better answered if one of the journal’s editor’s, such as Mark Levine himself, had demanded such a clarification prior to publishing. I actually think it’s irresponsible of him to make allusions to ethical violations when he clearly has/had some leverage to actually address the given question directly!

    Regarding the liver tests: Chabot et al. stated

    Bilirubin and albumen were significantly higher in the chemotherapy group, but all values were clinically within normal limits and met eligibility criteria.

    Diagnoses of liver metastases and other liver diseases is more typically associated with elevated bilirubin blood test levels. If anything, the chemotherapy would more reasonably be hypothesized to have a greater likelihood of liver metastases. Levine’s pondering doesn’t seem to make much sense…

    Furthermore, let’s play a thought experiment: pretend this study had no chemo control group at all, it was simply following the survival and quality of life of 32 patients on the Gonzalez protocol that couldn’t be cherry-picked in the same way as Gonzalez’s previous case reports (such as PMID 10368805) upon which he bases his boasts that his protocol has results that are

    far above the 25% survival at one year and 10% survival at two years for all stages of pancreatic adenocarcinoma reported in the National Cancer Data Base from 1995. This pilot study suggests that an aggressive nutritional therapy with large doses of pancreatic enzymes led to significantly increased survival over what would normally be expected for patients with inoperable pancreatic adenocarcinoma.

    He also proudly displays on his website case studies of individuals with 10-20 survival of pancreatic cancer that he attributes to his regimen. Now we have independent data on 32 patients under this type of care that clearly does not show the type of success Gonzalez has previously claimed. That seems foolish to deny. Of all the things we might learn from this flawed study, it seems most clear that the Gonzalez protocol did not perform consistent with Gonzalez’s claims of prior success, had survival numbers that compared unfavorably with historical data, and did not seems to confer any benefit to quality of life measures.

    Look, the Chabot et al. study isn’t great; it’s got plenty of flaws. The study should probably never have been done in the first place given the paucity of biological plausibility or published evidence in favor of such an intervention. It is, however, the highest-quality evidence to-date evaluating the Gonzalez protocol. If anyone has any actual evidence of violated ethics in this paper they need to present it to the relevant authorities. If there is any real evidence of unethical data manipulation, for example, I will seriously reconsider my position on this paper. Until then, however, these appear only to be empty insinuations that are themselves ethically dubious, in my opinion.

  84. #84 The other perspective
    November 30, 2010

    Here is Dr. Gonzalez explaining the inconsistencies between the results in his practice and the results in the study.

    http://www.dr-gonzalez.com/nci_nccam_timeline.htm

  85. #85 Oracle
    November 30, 2010

    Here is Dr. Gonzalez explaining the inconsistencies between the results in his practice and the results in the study. To eliminate bias within this commentary, I believe that everyone who has decided to conclude anything before reading this has done so prematurely, as many legitimate critiques of the study Dr. Gonzalez has detailed have not been addressed here by the beloved and seemingly un-biased “Orac”.

    http://www.dr-gonzalez.com/nci_nccam_timeline.htm

    I await further rebuttal.

  86. #86 Stay busy
    November 30, 2010

    3 things of which you’ve said:

    -I know of no science-based cancer protocol that requires a patient to consume 150 pills a day.

    -Sadly, the “scientific” rationale behind the Gonzalez protocol…etc

    -How such a study was ever approved by an Institutional Review Board, I’ll never know.

    Show me the “science-based, scientific rationale, Institutional Review Board approved” evidence for the implementation of this – http://www.kepstein.com/2009/07/30/“they-used-our-kids-as-guinea-pigs/

    You demonize Dr. Gonzalez for expediting the death of a couple dozen people in efforts to study a potential cure, but not only was this study robbed from him and completed improperly by Dr. Chabot who has ties and investment in the opposing gemcitabine treatment, but your cohorts who fund every dollar for your drugs and vaccines commit outright deception and fraud as shown in the above link (and thousands more that are mysteriously absent from your blog).

    You are either financially tied to your words or uneducated in your own field. Either way, you are arrogant and represent the western model of sick-care.

  87. #87 Steve
    January 31, 2011

    With the in depth study into flu vaccines by the Cochrane Library one wonders why the flu vaccine is still given at all, it’s almost as effective as Chemo for pancreatic cancer. 1% effectiveness versus NOT getting the flu shot, ZERO effectiveness against transmission.

    The UK three weeks ago ruled that the flu vaccine program will no longer be given to infants 6 months and up, but rather for those 5 years old and up. Good for them.

    Here we have the FDA and Health Canada (North America) still announcing on their websites that the best preventtion againts the flu is the flu vaccine, containing thimerosol, 2-PE, aluminium, MSG, formaldehyde, etc. Why would anyone take the flu shot when there are no studies done showcasing any effectiveness at all greater than 1%?

    Chemo is the biggest farce. Big Pharma used Lance Armstrong as a poster boy for chemo, yes chemo gives you the best chance at beating cancer, without mentioning that testicular cancer is one of three cancers that actually responds favourably to chemo.

  88. #88 Chris
    January 31, 2011

    Hi, Steve the Necomancer! What prompted you to grace us with your silly opinions after it was dormant for so many months?

  89. #89 Scott
    January 31, 2011

    Not just threadomancy, but also a complete lack of evidentiary support AND grossly off-topic! It’s a trifecta!

  90. #90 Orac
    January 31, 2011

    My guess: Someone was searching Google for the Gonzalez Protocol and somehow came across this almost year and a half old post. Steve’s also wrong: There are many other cancers that respond well to chemotherapy. There are also quite a few that do not, and, unfortunately, pancreatic cancer is one of the most chemoresistant.

    In any case, whenever necromancers start posting drive-by nonsense, it’s time to close the comment thread.