Nicholas Gonzalez is a controversial doctor practicing in New York.  He has been promoting for years a largely dietary treatment for cancer including an individualized organic diet, large amounts of supplements, and pancreatic enzymes. He is a case study in why we need rigorous science to decide which treatments are safe and effective, of the lure of quack claims, the power of bias, and the inadequacy of our current regulations.

Dr. Gonzalez has managed to have a thriving practice despite, in my opinion, violating the basic standard of care and medical ethics. He has done so partly by riding the wave of so-called “health care freedom” which confuses (I think deliberately) the public about the nature of standards in medicine.

The Gonzalez treatment, which is based on prior claims made by James Beard and William Kelley, lacks plausibility or basic science support. While you can find studies to show that an individual supplement may have some effect that potentially could have some clinical effect, you have to extrapolate wildly and recklessly from such information to clinical claims. Such information is at best a source of hypotheses – not treatments.

And in the final analysis Gonzalez’s claims are just recycled CAM propaganda – claiming that supplements will boost the immune system and detoxify the body.

Medical ethics also requires that before we subject patients to new treatments we at least test them in animals to have some idea about safety and at least the hope of benefit. There have been animals studies on the pancreatic enzymes, but not the treatment as a whole. The National Cancer Institute reports:

In 1999, an animal study tested the effect of different doses of pancreatic enzymes taken by mouth on the growth and metastasis (spread) of breast cancer in rats. Some of the rats received magnesium citrate in addition to the enzymes. Rats receiving the enzymes were compared to rats that did not receive the enzymes.

• Results showed that the enzyme did not affect growth of the primary tumor (where the cancer started).
• The cancer spread to the most places in the rats that received the highest dose of enzymes.
• The cancer spread to the fewest places in the rats that received the lowest dose of enzymes plus magnesium citrate.

Another animal study looked at the effects of pancreatic enzymes on survival rates and tumor growth in rats with pancreatic cancer. Rats receiving the enzyme treatment lived longer, had smaller tumors and fewer signs of disease, and were more active than the rats in the control group, which did not receive the enzyme.

So results are mixed at best, but the study showing a worsening of cancer with the treatment should have been cause for extreme caution before giving the therapy to humans.

Dr. Gonzalez did publish a case series of his treatment for pancreatic cancer, which is a particularly deadly form of cancer with a 1 year survival of only 2%. He reports that in his case series of 11 patient their average survival with his treatment was 17.5 months.  That is very impressive, if true. Proponents used this data to support the Gonzalez treatment and dismiss critics, while science-based physicians pointed out the fatal weaknesses of case reports – namely they are not controlled, and therefore are subject to a host of biases.

To resolve the dispute a prospective trial was planned, and the results of this trial have now finally been reported – four years after the trial was complete. Kimball Atwood gives a thorough discussion of the trial itself at Science-Based Medicine, so I won’t go into detail about the trial’s history. Suffice it to say it was controversial. There were significant ethical concerns about studying an implausible treatment with inadequate pre-clinical justification in a disease as serious as pancreatic cancer. Most curious and disturbing is, considering the results, the four year delay in making the results public. This is a scandal, in my opinion.

But finally we have the results and they show:

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).

That’s right – standard therapy mean survival was 14 months and on the Gonzalez treatment 4.3 months. That is a dramatic difference, and supports what critics have been saying for years.

There is only one weakness to the trial that I can detect – it was not randomized. The reason is that too many patients refused to be randomized. They did not say if patients refused to go on the Gonzalez treatment, refused not to go on the treatment, or both. Regardless, this opens the door for the claim that patients who self-selected to go on the Gonzalez treatment were sicker. There is no evidence to support this claim in the study and the researcher tried to compensate for the lack of randomization by making sure the two groups were as comparable as possible. So while this criticism is legitimate it is highly unlikely to explain the dramatic difference in  survival between the two groups.

The bottom line is this – that Gonzalez treatment is not only worthless it is harmful and reduces quality of life. This is an important cautionary tale. But first this raises an interesting question – how did Gonzalez get his impressive 17.5 month survival in his case series when a prospective study shows a 4.3 month survival? We will never know for sure – the possibilities include that some of the patients did not have pancreatic cancer (he says they were biopsy proven), but most likely is that he simply cherry-picked the cases that did well.

In any cases, this shows the relatively low value of case series. They are useful for detecting new phenomena and for generating hypotheses – but not for testing hypotheses, not for telling if a treatment works. This is a dramatic example of why we don’t rely on anecdotal evidence, and why science-based practitioners are appropriately dismissive of anecdotes.

But further, the Gonzalez case taken as a whole shows us that you can promote a treatment that actually causes harm and yet still create a faithful following, bamboozle regulators, charm the media, and delay (sometimes indefinitely) definitive testing of your claims.

It further justifies why many science-based physicians believe such trials are themselves unethical. The 32 patients in this study that selected the Gonzalez treatment were victims – they lost quality of life and on average 10 months of life. Was their sacrifice justified? I and others say no – before the Gonzalez treatment was given to a single person far more basic science and animal testing should have been done. Then, if the treatment looked promising and safe (at least equivalent to current standard treatment) small pilot studies in humans would be next, and then definitive clinical trials.

We use this sequence for a reason – because most new ideas in medicine are wrong. Because in order to “first do no harm” we need to proceed carefully with experimental treatments and only give them to people when there is sufficient plausibility and pre-clinical data to justify it. This is the ethical standard in medicine, but the public has fallen victim to the successful creation of a double standard with clever marketing of terms like “alternative,” “holistic,” “natural,” and “detoxify.”

Finally, I want to know where the media attention is on this issue. I only heard about it because of my involvement as a proponent of science-based medicine. This study was published online on August 17th and I have seen no mainstream coverage of it. (I’m sure it’s out there, but it certainly did not grab my attention.) The National Cancer Institute needs to update their website with this information yesterday. And I would really like to hear why there was a four year delay in the results being published at all – four years during which Gonzalez continued to use his therapy. He still is, and his website gives no hint that his claims have just been blown out of the water.

Now we have to wait and see what the response will be from Gonzalez and regulators. The true test of an ethical science-based practitioner is what they do in the face of evidence against a treatment they currently favor. The Gonzalez treatment, in my opinion, was never ethical and now it is outrageously unethical. It needs to stop immediately.