The Gonzalez protocol: Worse than useless for pancreatic cancer

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The 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:

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:

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:

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:

The two arms of the study were described thusly: