Karl:  In response to your post before this one re: natural treatments, I was wondering if you could share with the group any alternative treatments or clinics that you've tried, if any worked or didn't work, and what your observations were? 

Reply:  

There are many reasons why I was not prepared to objectively evaluate medical claims when Joanne was first diagnosed. The first, being I had no formal medical or scientific training.

I didn't get off to a good start either. I bought into the conspiracy theory described in a book called "Options." Coincidently, a neighbor gave us this book when Joanne was first diagnosed in 1996. It planted mistrust in the medical system - in the so-called "chemotherapy concession." I began to look at alternative medicines in earnest.

Instead of watchful waiting, "we" decided to try Burzynski's antineoplastons, mainly because we talked to patients who said it helped them. Some said they were cured. Burzynski also said he could cure Joanne. 
A non-toxic therapy that can cure! How could we not try that? Which illustrates my second deficit: I did not understand that testimonials are not evidence. 

A second reason we chose Burzynski was that this was one of the alternative protocols listed as potentially useful by Dr. Ralph Moss, PhD, in a personalized Moss report we purchased.  It's worth noting that it was not apparent that Dr. Moss's background and degree was not in medicine.

A third skill is knowing what you do not know. I lacked this too. Burzynski's peptide theory seemed plausible to me, and I had an arrogance that I was able to recognize good and bad theories about treatments for cancer. After all, I spent many *months* reading up on it! And since the medical establishment could not be trusted, I had better take this on myself.

The event that began to slowly awaken me was Joanne's medical crisis. The necessity to treat with CHOP to deal with fast progression in 1997. Joanne's brain was in a fog from 10 months on the 24-hour pump infusion of 
Buryzinski's peptides (which smelled like urine). Although she had a 30% response* at one point (or was it?), the lymphoma began to progress rapidly and was now bulky. New nodes were appearing almost daily. When "we" finally went off study, the gallium scan lit up like a Christmas tree. I recall that the liver involvement scared me the most.

* We can anticipate that the temporary response to antineoplastons is being cited by others as "evidence" that this therapy works, ignoring what happened later ( the transient nature of the response), and that indolent lymphomas will wax and wane spontaneously.

Thankfully, the CHOP put the lymphoma into remission, even at this advanced stage. Clearly, without effective standard medicine she would have died... and so, with our crisis, my firm belief in the conspiracy theory began to erode.

Unfortunately, the remission from CHOP was short lived, perhaps a cost of delaying treatment.   It lasted but eight months. Thankfully the biopsy indicated the lymphoma was still indolent.

But I was not yet a convert to evidence-based medicine. Slow learner. Believing myself capable of doing my own research (I still did not know what I did not know), I spent perhaps thousands of hours reviewing the literature for promising natural compounds. My research led to trying many alternative practices during Joanne's short remission, and for a short time after her relapse.

Still she progressed. Again, Joanne started her next standard treatment, Rituxan, with bulky disease - that is to say, at a disadvantage. For indolent lymphomas the *variable* natural history of the disease could 
easily account for the outcomes reported in testimonials. This is the context that we *must use* to more objectively review study reports and testimonials. It's documented that some people with fNHL have never needed treatment. Others need it quickly. Recently, evidence from gene profiling research (LLMP) has shown that fNHL is not one disease, but at least four diseases affecting the same cell type. ...

It's estimated from clinical records that ~70% of people with indolent lymphomas have a truly indolent course, and that 30% will regress spontaneously. The jargon for the underlying variability of a disease is heterogeneity. fNHL is a heterogeneous disease. See http://content.nejm.org/cgi/content/full/351/21/2159  for a description 
(free registration req.)

So I think it follows that if 100 people with fNHL tried alternative strategies, 70 could easily *feel* that it's helping, and 30 would be absolutely convinced. Testimonials would soon follow. But the same results 
would be expected from use of a placebo, or if you followed any group of 100 patients with fNHL.

Eventually, I gave up hunting for leads on natural approaches, but it was not because of our negative personal experience, or because the light went on about what it takes to know if an intervention is really helping ...

.. the bright light came on when I learned that in vitro (cell culture) experiments are unreliable as sources of evidence. The literature is littered with articles on the anti-cancer activity of natural compounds in test tube experiments. The problem is that cancer cells are no more like themselves when removed from the body than a fish is itself in soda water. ...

And this serious limitation of in vitro "evidence" is compounded by the second hurdle, which is bioavailablity: it is many times not feasible to take the oral dose needed to reach levels in the blood that showed activity in cell culture experiments. Often the body changes, or merely excretes, the active compounds. 

The promise of natural medicine gets even thinner when you examine the track record. The odds of success is roughly 1 in 5,000 that any compound showing activity in assays will win marketing approval (PHRMA report).

So for all of these reasons I think we are better served by looking at new agents that have reached at least phase I *clinical* development. That is, human testing. The compounds don't get this far without having shown activity and preliminary evidence in assays and animal models. Here the odds of reaching the market (being clinically useful - the benefits outweigh risks) improve to about 1 in 10.

We all want to believe that a non-toxic natural way to treat lymphomas is out there somewhere. It's only human. It should be noted that many times new treatment agents are analogs of natural compounds that have been tweaked to improve bioavailablity and to target molecular pathways with greater affinity. It's a myth that natural compounds are ignored by researchers and the pharmaceutical industry. Vincristine to name just one. There is an NCI department of Natural Products, which is dedicated to this work.  

The conspiracy theory raises the level and urgency of our personal pursuit to find natural medicines; it leads to reliance on untrained persons to find the way. The people who take the lead are sometimes sincere and 
intelligent, but this does not make them correct. A signal of their inner doubt, I think, is a reluctance to publish or share their ideas with professional scientists for review.

The conspiracy theory does not hold up to scrutiny. It can't address the 80% cure rate of childhood cancers with standard chemotherapy; or the fact that everyone gets cancer,  including researchers, doctors, regulators ... and their children. Or that a conspiracy would require the complicity of the parents of children with cancer.

It's a myth that natural medicines are kept from us to protect the profits of the industry. The profits are a necessary driver of the research. Patent law was designed to make the risky path of drug development worth trying. Most often they fail, and lose incredible sums of money. Only a few make it through the independent FDA review process. Yes, the industry has a bias. Yes, they have conflict of interest. This is why the role of FDA is vital.

I know that belief in the "evidence" supporting natural medicine can provide comfort and a sense of control. And I'd probably leave it unchallenged if the stakes weren't so high. That is, *strong belief* in unproven therapies can do harm if a person delays, or avoids, proven treatments because of it.

Alt med's appeal is understandable, particularly for cancers that have no effective treatments, but it's a red herring. There are many more promising directions in clinical research to review and participate in - ideas that are being developed by trained scientists and independently reviewed; that are built on a growing body of scientific evidence based on scientific method: controlled studies that demonstrate. instead of merely claiming safety and efficacy.

We might better exercise our energy and apply our intelligence to advocate for standardized biobanks and routine gene profiling so that we can learn what molecular signatures correlate with prognosis and response to different treatments, and more rapidly identify new drug targets. We might participate in clinical trials that test immune and biological therapies that may be many times safer than chemotherapies ... We might inform the industry about obstacles to trial participation, or help to increase investments in cancer research.

~ KarlS

Postscript:  Ten years later, Dr. Burzynski has still not published his outcome data on lymphomas. 

JoanneS DX 1/96 = nhl-low follicular, Stage III, no bone marrow
involvement - initial W&W, but with progression

11-96 Antineoplaston Clinical trial 
PR - 30%, followed by progression ...

11-97 ... suspected transformation, not confirmed by core biospy

12-97 6 x CHOP 

CR , relapse 8 mo DX = same as original (low grade)

12-99 Rituxan 8x 
Stable

06-00 LL-2 (anti-cd22) Clinical trial 
Stable

04-01 Rituxan 4x (4/20) seq with oral low dose PEP-C 
PR ~ 80%

12-01 Repeat PEP-C 
PR ~ 70%

04-02 Favrille idiotype vaccine 
Stable

11-02 Rituxan + CpG Clinical Trial 
Stable

01-03 oral low dose PEP-C 
PR ~ 80% 

04-03 Inteferon-alpha-2b
(rationale: to maintain response during rest)

07-03 Favrille idiotype vaccine Clinical trial 
Stable

07-04 MRI detects some progression.
Begin oral low dose PEP-C 4 week + 2 week every other day 
Result: ~ 90% response *
Bone marrow negative (PCR)

11-04 High dose cytoxan, Neupogen, Stem cell harvesting
(Harvesting while PCR negative, 
as precaution, and to reduce tumor burden further)

02-05 Bexxar
(Neck nodes increased by 5x after dosimetric dose,
probably inflammation)

01-09 No palpable nodes detected (~4 yrs out)