 |
DOES IT WORK OR NOT?
The evidence from both formal and informal trials suggest there is some possible benefit from decoppering. Both in the formal and informal trials there are a number of patients who have survived for several years while on the decoppering regimen. However it does not work on all patients, and it may only be a temporary solution for many other patients. So little is known about the long term effects, there is a strong need for ongoing research.
The reports, for example, from informal trials include both cases where patients report outright disappearance of turmors, and those who report no benefit. But there are also cases where the results are ambiguous.
Future work will have to address a major failing of informal clinicals: The ad libitum mixing and matching of other compounds ranging from conventional chemotherapeutic agents to restricted diets and nearly mysterious "nutriceuticals" and extracts. The search for what works for cancer patients facing certain death produces an astonishing array of combinations that need to be organized and studied for greater insight. But without that, all of this becomes a pure nightmare for scientists. The hopelessly convoluted array of confounding variables destroys any chance of saying anything definitive and certainly impairs the ability to decide what to concentrate on in order to find what really works.
It can only be hoped that some way of connecting the information of both formal and informal clinicals will produce a body of clinical data that informs future treatments.
One special note here is that the term "decoppering" has two senses here. The first is to lower the copper level in the body to a target value that is below normal. The second sense is to lower copper from dangerously high levels, as seen in Wilson’s Disease patients, down to a normal level.
WHAT ARE THE SIDE EFFECTS?
Among the major concerns are anemia and low white blood cell counts. For these reasons alone it is critical that a trained physician monitor CRT patients at all times. In addition, there are side effects from the drugs. There also appears to be some art in how they are best administered in order to minimize the side effects. In the cases where patients cannot tolerate one decoppering drug, they switch to another.
Another side effect that is of concern is enlargement (hypertrophy) of the heart muscle that can result from low copper conditions. Also, on the TM drug, though the most benign, some patients have reported worsened neuropathies. Copper is also an important cofactor in hemoglobin synthesis.
One significant concern that remains unresolved is whether or not lowered copper presents a greater risk of liver tumors. This is particularly odd because the liver has the highest concentration of copper of any organ in the body. There are some cases where lower copper appears to have reversed growth of liver tumors, but then there has been at least one study suggesting otherwise.
THE MYSTERIES OF COPPER METABOLISM
How copper is utilized in the body is astonishingly complex. Each organ in the body appears to have its own mechanisms for storing and releasing copper. Each organ needs copper to varying degrees. The liver will surrender copper easily while the brain is exceptionally stingy with copper. Also, zinc competes with copper for a place in some proteins. If the ratio of zinc to copper is altered that can alter a person’s health prospects.
Also, when decoppering, a number of patients report extraordinary variations in the rate and pattern of decoppering. Values can suddenly drop, or they can be at a low level and then suddenly spike up. There can be a veritable roller coaster ride of serum copper levels from month to month. The reasons why are not always clear. So, this illustrates that even though copper metabolism has been a subject of study for at least 70 years, there is still much to learn. For example, copper chaperones were discovered just five years ago in 1997, even though chaperones had been known for much longer than that.
THE DRUGS USED FOR DECOPPERING
To date, there are three drugs for decoppering: Tetrathiomolybdate [TM], Penicillamine, and Trientine. TM is the newest, and appears to be the best tolerated. Penicillamine has been used the longest and is still regarded by many physicians as the drug of choice. Trientine is used by patients who cannot tolerated the side effects of penicillamine. They all require several months time in order to achieve the target levels for decoppering.
Emphasis must be put on the point that these are the drugs known and used to date. Other possible drugs for decoppering exist. They just have not been found yet. Short of that, some patients have tried novel approaches to decoppering. In some cases, high zinc intake could slowly lower copper levels. Some have found that a combination of "natural agents" rich in sulfur and certain amino acids can achieve decoppering target levels. However, this should be considered anecdotal until there is better evidence. Nonethelss, it illustrates the fact that there may yet be found even better methods of decoppering than are currently in use.
COMBINATION THERAPIES WITH COPPER
Combination therapies constitute an area that is just emerging. Formal clinical trials have just started to look at the effect of radiation with decoppering. There is a host of chemotherapeutic agents and anti-angiogenesis agents to try in conjunction with decoppering. It is entirely possible that a number of anti-angiogenic agents that had been considered failures may actually succeed when used with CRT. The recognition that angiogenesis functions by several different mechanisms suggests a strategy where if some number of those mechanisms are inhibited, then the tumors will fail to grow.
Currently, there is some growing interest among some oncologists about the possibilities of using CRT in conjunction with low dose chemotherapy. The apparent logic is that since CRT can be a long term therapy, if other medicines can be administered which can also be tolerated for a long time, then this may be a way of managing cancer. This could be called a "you hold 'em while I hit 'em" type of strategy. One concern is that even under low dose conditions, tumors could develop resistance. If CRT impairs the mechanisms for developing resistance, that would be a great help. At this point though, how combination therapies would affect resistance is basically unknown.
The other critical issue with combination therapies is what constitutes the best "strategy" in the sense of which combination of mechanisms need to be attacked? Among the properties of cancer cells that need to be addressed are: Motility, angiogenesis, proliferation and penetration. Will stopping any two of those do the job? Will complete stoppage of just one do the job? Or will it ultimately be required that all the key mechanisms be brought to a halt?
RELATED INTERVENTIONS
The related interventions most commonly discussed are zinc supplementation, lowering iron levels in the body, and reducing sugar levels. The CuZn Yahoo group has extensive discussions on these subjects. There is also some discussion about other agents that get mentioned from time to time. Collectively, they represent a body of alternatives that need additional investigation. These related interventions are potentially very important, but as noted above, are a scientists nightmare. Each subject can be focused on separately, but there will come a time when it all needs to be integrated into one system for the benefit of both patients and doctors.
RETHINKING DECOPPERING
Decoppering raises at least two other issues: 1) The redundant systems in the body for angiogenesis, and 2) The larger academic question of how all metals interaction with amino acids and proteins in the body. On the first point, there has been some discussion recognizing that some angiogenesis may be copper-independent. In those cases, cancer patients would presumably not benefit. However, it is not clear if zinc has some secondary role besides competing with copper that could impact on angiogenesis, or stimulate it. A more complete picture needs to be produced by further basic research into the underlying mechanisms. For example, what is known about the relationships between various metal chaperones and angiogenesis? Can chaperones be manipulated to control angiogenesis? If, for example, Wilson’s Disease is a case of mutated copper chaperones, mutating cancer-specific or angiogenic-specific chaperones might kill tumors. But again, more research is needed to answer such questions.
The subject of interactions between metals and proteins is a huge and awesomely complex area, but it is also one that can produce key insights into the most fundamental mechanisms of life, as well as the basis for the origin of life. Dr. Brewer noted that copper appears to have played a significant evolutionary role across species in a variety of growth and repair mechanisms for the body. If, for example, molecular evolution for the ultilization of certain metals is particularly conservative across time, then that would suggest a relationship that could lead to other types of therapeutic interventions in cancer and other diseases.
BEWARE OF CONFUSED INFORMATION...
There is enough inconsistency in research to demand that patients be skeptical at all times. In one case, a researcher may draw a certain conclusion from the results of the experiment. However, closer scrutiny would reveal that the results may be correct, but the conclusion does not logically follow from the results. In another case, results of one researcher cannot be replicated in other labs. Or, different researchers will announce contradictory results. For example, one researcher, in his lab, can show that a drug stimulated apoptosis. But, later, another research may show that the same drug block apoptosis. All of the above are actually common problems. In addition, there was the recent admission by the Journal of the American Medical Association, that they have been unduly influenced by drug advertisers, that their peer review is not always so good, and that the quality of the studies they have published in the past have been less than stellar.
Confession is good for soul, and even for publishers. It is a recognition that vigorous debate is critical to intellectual progress. So, also, with the considerable volume of confused information, there needs to be loud and persistent warnings conclusions are unwarranted.
...AND, ABOVE ALL, REMEMBER THE CANCER PARADOX!
Cancer is a contradictory disease. Epidemiologists note that infectious diseases tend to evolve to a more benign state so they don’t kill the host. This confers survival advantage on the more benign agent. Cancer is self-destructive. It has not evolved to any benign state, but there are enough different cases of remissions, and other changes to make any generalization impossible. Nonetheless, there is another dimension to the cancer paradox that is important to keep in mind: A drug that kills one cancer, may feed another cancer. That can include tumors of the same type, but which mutate over time.
TIMELINE AND NEWS
January 2000 – Results of first Phase I trial for decoppering cancer patients announced by Dr. Brewer and coworkers
March 2001 – First decoppering board started on Yahoo
November 2001 – Second decoppering board started on Yahoo
Feb. 25, 2002 - Dr. George Brewer recently spoke at a nutrition conference in San Diego, CA. He described some of the current work and discussed future directions for CRT.
FORMAL CLINICALS
1. Results of a Phase II clinical trial managed by Dr. Stephen Brem at the Moffitt Center has been pending since at least September 2001. Dr. Brem has noted that the data is still being evaluated.
2. A Phase II trial at the University of Michigan is also in process. It will be at least a year before results are learned from that trial.
INFORMAL CLINICALS
There are at least two known chat boards dedicated to understanding decoppering for treating cancer. There may be other groups, but if they exist, they have not been found yet. For information about informal clinicals, please contact Sue Gallant at ElCajonSue@aol.com.
|
|
|
