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Integrative Medicine for Colon Cancer - Part 1

by Nicholas Calvino DC(more info)

listed in cancer, originally published in issue 98 - April 2004

Conventional Cancer Care Overview

The World Health Organization has estimated there will be more than ten million documented new cases of cancer next year. Since 1971 according to official figures, over $1 trillion has been spent on conventional cancer research and treatment in the US The current cost is at least $110 billion a year – over 10 percent of all US medical expenditures, and two percent of the entire GNP. Despite, or perhaps because of these unprecedented costs, the cancer establishment remains largely closed to most truly independent, innovative treatments. More people make a living from conventional cancer research and treatment than die from the disease on an annual basis. The average cancer patient spends in excess of $100,000 treating the disease via the conventional medical protocol. Thus, there is a tremendous vested interest in the status quo of current cancer therapy. A 1986 report in the New England Journal of Medicine assessed progress against cancer in the United States during the years 1950 to 1982. Despite progress against some rare forms of cancer, which account for 1 to 2 per cent of total deaths caused by the disease, the report found that the overall death rate had increased substantially since 1950. "The main conclusion we draw is that some 35 years of intense effort, focused largely on improving treatment must be judged a qualified failure." The report further concluded,"We are losing the war against cancer."[2]

Colon image

Clearly, there are appropriate conventional treatments that seem able to remove the immediate threat to life. Surgery, chemotherapy and radiation are used with some degree of success in killing cancerous tissue. However, that degree of success must be weighed against the possible side effects and after effects that are to be expected. For a period of time in the mid-1970s, Nobel laureate James Watson, one of the world's most respected biologists, repeatedly called the war on cancer scientifically bankrupt, therapeutically ineffective and wasteful.[1] In 1975, reporter Daniel S Greenberg broke a virtual media blockage with a celebrated piece in the Columbia Journalism Review (CJR). This was the first time a respected journalist had dared to openly criticize the cancer establishment. The article quoted criticisms by oncologists and statisticians working within the 'war' itself. In March, Greenberg wrote a follow-up article for the New England Journal of Medicine. Both articles showed that many of the claims of progress in the 'war against cancer' were a sham, a statistical construct.[2] What this research, and current research today show, is that survival rates for the most common types of cancer (those that make up 90% of cases), have remained virtually unchanged, except in the forms of rare types of cancers and one or two other exceptions.[3,4] Patients with advanced disease are often told their treatment will do more good than it is likely to and chemotherapy is presented as more effective (and less toxic) than it really is.

The side effects of chemotherapy are routinely understated. Proof of this is the discrepancy between what oncologists tell patients to do, and what oncologists themselves do (or would do) if they have cancer. Do they believe in their own treatments so much that they would take it themselves? When celebrated chemotherapist Dr Kettering found out he had advanced cancer, he told his colleagues, "Do anything you want – but no chemotherapy!" And when Dr Kettering's mother got cancer, she was sent to Germany for unconventional treatment. Further proof of medicine's own lack of belief in some forms of oncology was a shown in 1986 when McGill Cancer Centre scientists sent a questionnaire to 118 doctors who treated cancer. All of them were affiliated with the Princess Margaret Hospital in Toronto or with the Ontario Cancer Research and Treatment Foundation, which operates seven cancer clinics. These Canadian specialists were asked to imagine that they themselves had cancer, were asked if they would they consent to chemotherapy. 74% of specialists would not consent to chemotherapy. The reason they gave: the ineffectiveness of chemotherapy and its unacceptable degree of toxicity.[5]

Generally, patients treated with chemotherapy have good initial results, but this results in a poorer long-term prognosis. For example, in two studies in which previously untreated patients were given paclitaxel with platinum compound, between fifty-nine and eighty-two percent of treated patients responded to therapy. However, these patients showed recurrent disease rather quickly, with median progression free survival times of roughly seventeen months being reported. In studies where this regimen was given to patients with recurrent cancer, results were more variable but generally worse. Moreover, median progression-free survival times as low as three months were reported, with median overall survival times ranging eight to thirty-one months.

The medical establishment's open criticism of Integrative or Alternative Medicine, is said to be its lack of research, specifically, the holy grail of Randomized Controlled Trials (RCTs). However, this criticism is largely untrue; although it is true there are a lot of unsubstantiated therapies in the alternative medicine arena. Nonetheless, there is a lot of research on many integrative therapies; however, there is a bias against them. For instance, much of the research published on these therapies occur outside the US and are published there, where alternative therapies are more accepted. US publications have shown that there is a research bias among US Medical Doctors and the Medical Establishment against accepting non-US articles or publications as valid – a kind of 'scientific nationalism'. Also, there is a bias among many medical journals against publishing research on natural therapies. Furthermore, there is a financial disincentive against funding such studies. Since most natural therapies cannot be patented, they are not attractive to pharmaceutical companies, which fund a significant portion of all research in the US Finally, although many of these studies on integrative therapies appear in peer reviewed journals, many are journals that conventional doctors do not read.

The argument against a scientific basis for alternative medicine is not valid, and in fact, it is hypocritical. Less than 20% of all medical therapies are backed by the holy grail of RCTs, and in the case of chemotherapy and cancer treatment, it may be less. Although RCTs are done on chemotherapeutic agents, 90% are done comparing one chemotherapeutic agent to another. There is little data comparing the effectiveness of chemotherapeutic agents to 'nothing alone' or to 'alternative therapies.' Most chemotherapy agents aren't proven useful, they are just proven less harmful than another or more effective than another. And if statistical 'Jerry Mandering' isn't enough, political pressure from lobbyists have convinced states and governing bodies to pass laws that make it a crime to treat cancer with anything but chemotherapy, radiation and surgery – intimidating those who would like to carry out valid research with non-status quo therapies.

Another way the data about the effectiveness of chemotherapy is twisted is 'dose effect studies' which attempt to find out whether higher doses of drugs cause longer survival. If patients in a high-dose study live longer than lower dose ones, one might assume the high-dose regimen is the better of the two. But this is not always true. For often the high-dose study requires that patients be in better overall physical condition before enrolling.

Another argument given by the medical establishment to validate the effectiveness of the 'war on cancer' is historical trends, which shows an upward trend in survival for almost all forms of cancer. However, there has been improvement in survival even of untreated patients over the years. This increase in survival across the board, is more likely to be due to better supportive care, earlier detection, and a general increase in life-span.[6] Even though proponents of chemotherapy believe better chemotherapy is responsible for the increase in cancer survival, viewed historically, careful analysis of the statistical data show that age-adjusted cancer rates are actually stable or on the increase.[7] This sort of historical analysis used by proponents of chemotherapy is regarded by statisticians as the weakest form of indirect evidence. The National Cancer Institute agrees with this.[8]

Unfortunately, in cancer research there is existence of bias and even fraud. For example, in 1994, one of the largest and most important chemotherapy testing trials, National Survival Adjuvant Breast and Bowel Project (NSABP), was the subject of investigations of unethical behaviour and fraud. The issue was known three years prior by the Office of Federal Research Integrity, but never reported. What is so significant, however, about this one case is that the entire basis of chemotherapy is built upon the program, which was the basis for the study. The program started in 1954 as the first randomized trial of chemotherapy for breast and bowel cancer and was the outcrop of the formation of the Cancer Chemotherapy National Service Centre, a division of the NIH (National Institutes of Health). Is this type of unfortunate conduct and misrepresentation representative of all cancer research? No. However, Dr Bernard Fisher's response (the head of the project) was not very reassuring: "I challenge those in authority to audit other clinical trial databases and see how well they fare."[9] It is likely that many studies would not fair well. In order to make their results appear better than they really are some researchers often employ "strategies of torturing their data until it confesses."[10] Recent studies have shown that 50 percent of faculty members reported that they had been exposed to two or more types of misconduct and questionable research practices (American Scientist,[11-12/93]).

Response Rates vs. Survival

It is one of the common misconceptions of chemotherapy that 'shrinkage, or 'response rates' have been proven to correlate with increased survival time. Yet, in answer to a patient's question, "What are my chances?", the doctor may give impressive-sounding response rates of, say, 60 percent. You need to understand that response rates do not often correlate with increased survival or improved quality of life. Response rate alone is a poor parameter by which to assess therapeutic benefit in cancer and does not predict survival. And its effect on quality of life is very much determined by the nature of the treatment used.[11] This makes chemotherapy seem more effective than it is. The FDA defines a 'response' in cancer as a reduction by 50 percent or more in all measurable tumours for 28 days or more. It is easy to see how this terminology can be misunderstood, especially when talking about drugs that really don't increase lifespan or absolute survival. Even more confusing is the talk of 'disease-free survival' rates, which implies a cure, but really means something different. Even more confusing is that disease-free survival is not equivalent to absolute survival. Response rates can be as high as 90%, but disease-free survival rates only 10%. Big difference! Much of the research done on chemotherapy today, uses 'response rate' as the only criteria for gauging the effectiveness of that agent. Disease-free survival refers to an increase in time that the patient is free of cancer before a relapse occurs. Absolute survival is increased lifespan. Almost none of the studies on chemotherapy are measuring absolute survival.

Other biases, intentional and unintentional, exist in interpreting the usefulness of chemotherapy, and include such things as lead-time biases, stage migration, publication biases, and selection biases. Although beyond the scope of this paper, I highly recommend the book: Questioning Chemotherapy, by Ralph Moss, PhD, that illustrates the complex issues behind research and the fallacies of interpretation.

Chemotherapy is a dose-limiting treatment. That means at a certain point doctors have to stop giving it or it will kill the patient. Guyton's textbook on medical physiology (standard in many medical schools) states: "The goal of chemotherapy is to kill the cancer, before it [chemotherapy] kills the patient." Furthermore, some chemotherapy agents actually cause cancer. The International Agency for Research on Cancer (IARC) has identified 20 singe chemo agents or regiments which cause cancer in humans, and about 50 more which are suspect. For example, one study showed that survivors of ovarian cancer treated with chemotherapy have a 100 times higher incidence of leukaemia. This phenomenon is called 'secondary cancers' which are caused by chemotherapy employed to treat the 'primary cancer'. By combining various forms of chemotherapy and then mixing them with radiotherapy, the risk of secondary cancers is increased. Chemotherapy can also promote the resistance of tumours to treatment, the occurrence of metastasis, and can suppress the immune system, damage the vascular system, and act directly in a thoroughly unpredictable way on tumour cells.[12]

Cancer is a systemic, not a local disease

"Let me tell you what really convinced me that the immune system has a lot to do with cancer," relates Neil Riordan, MS, PA-C, Founder and Director of Aidan, Inc. "There was a paper published in the Annals of the New York Academy of Sciences in 1993 by Dr James McCoy. It was a study of women with breast cancer. They had 77 women enrolled who were about to undergo surgery. When the surgery was performed they took tumour tissue and co-cultured this tissue with the patient's own lymphocytes (white blood cells). In some of the women, the lymphocytes had no reaction to the tumour tissue, and in other women the lymphocytes were stimulated and proliferated. This was nothing but the women's own natural immune response. Then they followed these women for more than 12 years. At that time, 47% of those women who showed no immune response had died. But of those women who had had an immune reaction, 95% were still alive." People develop cancer, says Riordan, because of 'immune tolerance'; that is, their immune systems are tolerating these tumours or cancers to grow. "The whole idea is to break immune tolerance," Riordan says. "If you have a tumour, then your body is letting it be. Otherwise, it would have rid itself of the tumour a long time ago, before you could even feel it. And that immune tolerance is what we're all about. That's what we try to get rid of."

Riordan finds that by rescuing and rehabbing the immune system cells with unique, advanced methods, the patient's immune tolerance transmutes into immune competence. This means that the patient's immune system recognizes, attacks and destroys tumours and cancer cells, with lower doses, thus avoiding their destructive side effects. Cancer, therefore, is partly a failure of the immune system, and all forms of treating cancer should include support for the immune system. The problem with chemotherapy is that it destroys the immune system. Therefore, use of chemotherapy in my opinion is best if it is short-term, and in combination with scientifically sound nutritional strategies. Long-term chemotherapy increases the risk of side effects.

Colon Cancer

Colon Cancer Overview

Colon cancer is the second biggest cancer killer in the United States and other industrialized countries, after lung cancer. It is strongly linked to a diet heavy in red meat and animal fat, as well as to smoking and heavy alcohol use, nutritional deficiencies and low fibre intake. A study, which appeared in the 1998 issue of the Proceedings of the National Academy of Sciences found a human gene that stops the growth of cancer cells when activated by fibre processing in the colon. In 1995, there was an estimated 140,00 new cases of colorectal cancer in the US About half that many die each year from colorectal cancer.

In its early stages, localized colon cancer is considered curable through surgery. Most if not all colon cancers are now believed to derive from pre-malignant polyps in the intestinal tract which nutrient deficiencies are documented to play a major role in their aetiogenesis.[13] Unlike other cancers which use a staging system of Roman Numerals (e.g. stage I-IV), or the TNM system, colon cancer staging is based on what is known as Duke's staging (named after pathologist, Cuthbert E Dukes). Dukes' A is essentially the equivalent of stage I, Dukes' B1 and Dukes' B2 of stage II, Dukes' C1 and Dukes' C2 of stage III, and Dukes' D of stage IV. While surgery is largely 'curative' in early stages, the five-year survival rate in Dukes' D is only 5 percent. In stages Dukes' A, B and C, the primary treatment of choice is surgery. In Dukes' B, five-year survival rates are 70 to 80 percent. In Dukes' C, survival rates for five-years have been stated from 5 percent to 70 percent. The confusing issues stems from contradicting data, concerning the use of certain chemotherapeutic agents, 5-FU and levamisole. It has now been shown that 5-FU has benefit, whereas, levamisole may be detrimental. Whether one or the other is used, or whether both are used in combination, determines the 5-year survival rate. 5-FU used alone shows the greatest positive impact.[14-18] In Dukes' D, where the cancer has already spread to distant sites surgery is sometimes palliative, but the disease is considered virtually incurable by conventional means.

Nutrition and Colon Cancer Overview

Long-term use of multi-vitamins may reduce the risk of colon cancer by 50 percent. Consumption of 200 international units (IU) of vitamin E per day may reduce the risk by 57 percent. A new study published in the October 1997 Journal of Cancer, Epidemiology, Biomarkers and Prevention shows there is a significant relationship between supplemental use of vitamins A, C, E, folic acid and calcium and lower colon cancer rates. Another study, published in the Journal Nature Medicine in 1997, found Vitamin E enhanced the cancer-fighting effects of five-fluorouracil (5FU), a chemotherapy drug regarded as the most effective treatment against colorectal cancer.

Intestinal Ecology and Colon Cancer

A paper in Nutrition and Cancer (1997:27:250) studied high- and low-risk diets and their relationship to gut flora-associated biomarkers of colon cancer, and increased beta glucuronidase activity. The study showed that a high-fat, low-fibre, high-refined-carbohydrate diet increased beta glucuronidase, whereas a diet high in protein, higher in unrefined carbohydrate, lower in fat, and rich in fibre (particularly fibres such as those of the fructooligosaccharide family like inulin) lowered the beta glucuronidase and the risk of colon cancer. One benefit of the indigestible carbohydrates found in fibre is, that they can be fermented by friendly bacteria in the gut to produce short-chain fatty acids like acetate, propionate, and (probably most important) the 4-carbon, short-chain fatty acid butyrate. Colonocytes (intestinal cells) use butyrate as a fuel. Butyrate is produced by gut bacteria through fermentation of non-digestible carbohydrate, is also very important as an anti-cell-transforming agent. It helps keep genes in the colonocytes in order, so to speak, to prevent the up-regulation of onco-genes. Therefore, production in the stool of the 'friendly' short-chain fatty acids, acetate, propionate, and butyrate, is very important and can be assessed with commercially available laboratory testing.

The intestinal microflora number in the trillions and are comprised of 100 to 400 different bacterial species. Maintaining the delicate balance of intestinal microflora is critical. Microbial balance is a key factor that determines whether substances in the intestine are converted into compounds that are beneficial or detrimental to the host.[19] There is considerable interest in the metabolic activities of the intestinal microflora, especially in relation to the aetiology of colon cancer.[20] Epidemiological studies indicate a correlation between regular consumption of fermented dairy products and low incidence of colon cancer.[21,22] To investigate this, several studies measured faecal bacterial enzymes, such as b-glucuronidase, nitroreductase, and azoreductase, which have been shown to catalyze reactions that convert procarcinogens to carcinogens.[21] In one study oral administration of L. acidophilus to meat-fed rats substantially reduced the activities of these faecal bacterial enzymes.[21] Similarly, in a study with seven human subjects, it was found that supplementing the diet with L. acidophilus for one month significantly reduced faecal b-glucuronidase and nitroreductase activities.[22] In a larger study with 21 human subjects, reductions of 2- to 4-fold in the activities of the three faecal enzymes were observed during a 4-week period of L. acidophilus supplementation.[22] To investigate the role of L. acidophilus in prevention of chemically induced colon tumours in rats, two groups of rats were challenged with a colon cancer inducing agent.[20] The experimental group, which was fed a supplement of the L acidophilus strain, showed a lower incidence of colon cancer after a 20-week induction period than the control group.

In researching how diet affects colon cancer British and American subjects on a typical Western diet with a high proportion of meat in their diet were compared with Indian and Ugandan subjects who consumed strict vegetarian diets. Subjects with significant amounts of meat in the diet were found to have many more gram negative, non-spore forming anaerobes such as Bactericides in their faeces, whereas subjects who consumed a vegetarian diet were found to have a higher proportion of Streptococci and Enterobacteriaceae. Therefore, the anaerobe to aerobe bacterial ratio was higher in those people consuming a typical Western diet, manifesting in individuals as an increased risk of colon cancer.[23] Kruis et al reported significant increases in gut transit time, fermentative colonic bacterial activity, and intestinal bile acids in healthy subjects who were fed a diet high in refined sugar. The lengthened transit time caused an increase in secondary bile acid concentration, which may be associated with the development of colorectal cancer.[24]

Two recent papers discussing Lactobacillus acidophilus stimulating production of trophic factors from murine macrophages and Bifidobacteria showed they inhibited colon cancer by modulating intermediate biomarkers of colon carcinogenesis.[25,26] These studies again looked at various kinds of biochemical markers for colon carcinogenesis and showed they are lower after supplementation with Bifidobacteria, and improved after supplementation with Lactobacillus acidophilus.

To Be Continued.

Part II will fully consider many nutritional elements in the treatment of colon cancer.

References

1. Greenberg D. A Critical Look at Cancer Coverage. CJR. Jan-Feb: 40-44. 1975.
2. Greenberg D. Progress in Cancer Research – don't say it isn't so. NEJM 292: 707-708.1975.
3. Illich I. Medical Nemesis: The Expropriation of Health. Bantam Books. NY. 1976.
4. Braverman A. Medical Oncology in the 1990s. Lancet. 337: 901-902. 1991.
5. Hansen HH. Advanced non-small cell lung cancer: to treat or not to treat? JCO. 5: 1711-1712. 1987.
6. Rankin EM. Non-small-cell Lung Cancer. Slevin and Staquest. 447-491. 1986.
7. Ries, LAG, et al. Cancer Statistics Review 1973-1990. Bethesda. NCI. 1990.
8. Miller BA et al. SEER Cancer Statistics Review: 1973-1990. NIH Pub. No. 93-2789. Bethesda. MD: NCI. 1993.
9. Crewdson J. Head of Federal Cancer Institute Plans to Resign. Chi. Trib. 22.12.1994.
10. Smigel K. Experts agree to disagree on adjuvant therapy for breast cancer. JNCI. 82: 640-641. 1990.
11. Macaulay V and Smith IE. Advanced Breast Cancer. Slevin and Staquest. 273-258. 1986.
12. McMillan TJ and Hart IR. Can Cancer Chemotherapy Enhance the Malignant Behaviour of Tumours? Cancer and Metas. Rev. 6: 503-520. 1987.
13. Weir DG and Scott JM. Colonic Mucosal Folate Concentrations and their Association with Colorectal Cancer. Am J Clin. Nutr: 68: 763-4. 1998.
14. Mortel CG et al. Levamisole and Fluorouracil for Adjuvant therapy of Resected Colon Carcinoma. NEJM. 322: 352-358. 1990.
15. Steele GDJ et al. National Cancer Data Base: Annual Review of Patient Care. Atlanta: American Cancer Society. 1994.
16. Chlebowski RT et al. Late mortality and Levamisole Adjuvant Therapy in Colorectal Cancer. Brit J Cancer. 69: 1094-1097.1994.
17. Davis S et al. Combination Cyclophosphamide, Doxorubicin and Cisplatin (CAP) Chemotherapy for Extensive Non-small Cell Carcinomas of the Lung. Cancer Treat Rep. 65: 955-958.1981.
18. National Cancer Institute. PDQ. Statement on Colon Cancer. 4.14.1994.
19. Donaldson RM. Normal Bacterial Populations of the Intestine and Their Relation to Intestinal Function. NEJM. 270: 1050-56.1964.
20. Goldin BR, Gorbach SL. The Effect of Milk and Lactobacillus Feeding on Human Intestinal Bacterial Enzyme Activity. Amer J Clin Nutr: 39: 756-61.1984.
21, Goldin B Gorbach SL. Alterations in Faecal Microflora Enzymes Related to Diet, Age, Lactobacillus Supplements, and Dimethylhydrazine. Cancer: 40: 2421-26.1977.
22. Goldin BR, Swenson L, Dwyer J et al. Effect of Diet and Lactobacillus Acidophilus Supplements on Human Faecal Bacterial Enzymes. J Nat Cancer Institute. 64: 255-61.1980.
23. Hentges R. Does Diet Influence Human Faecal Microflora Composition? Nutr Rev. 38: 329-335. 1980.
24. Kruis W, Forstmaier G, Sheurlen C, Stellard F. Effects of Diets Low and High in Refined Sugars on Gut Transit, Bile Acid Metabolism, and Bacterial Fermentation. Gut. 32: 367-371.1991.
25. Hambly RJ, Rumney CJ, Fletcher JM, Rijken PJ, Rowland IR. Effects of High and Low-risk Diets on Gut Microflora-Associated Biomarkers of Colon Cancer in Human Flora-Associated Rats. Nutr Cancer. 27(3): 250-255. 1997.
26. Singh J, Rivenson A, Tomita M, Shimamura S, Ishibashi N, Reddy BS. Bifidobacterium Longum, a Lactic Acid-Producing Intestinal Bacterium Inhibits Colon Cancer and Modulates the Intermediate Biomarkers of Colon Carcinogenesis. Carcinogenesis. 18(4): 833-841. 1997.

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About Nicholas Calvino DC

Nicholas Calvino DC is a practising clinician, nutritional consultant and author and lecturer on the subject of health and nutrition. He is currently the president of Natural Health Partners, LLC, a practice 'enhancement' company focusing on assisting doctors in marketing and managing secondary profit centres. He can be contacted at PO Box 160, North Street, MI 48049; Tel: 810-385-6737; drcalvino@msn.com

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