We Can Reduce Cancer Deaths by Half

The possible reduction of cancer deaths involves for the most part, the prevention of death from cancer metastases, for 90% of all cancer deaths are caused by metastases. One could say that what is being proposed is adjuvant treatment for all forms of solid malignant tumors.

We now have the widespread use of adjuvant treatment for one form of cancer only, breast cancer. An overview of 61 trials carried out in our Western world over the past ten years was reported in the New England Journal of Medicine for December 29, 1988. In this review it was reported that among 16,513 women over age 50 maintained on tamoxifen for a period of one to two years after discovery of the malignancy, there were nearly 4,000 deaths in the five post discovery years. As compared to untreated controls this represented a reduction in deaths at the 5th year of about 1/5th.

Among 13,442 women under age 50, a bit over 4,000 women died in the first five year period who had had combination cytotoxic chemotherapy for a mean average time of six months after discovery. This represented a reduction of 1/4th the deaths as compared to women receiving no treatment at all. It should be mentioned here that most oncologists will put abreast cancer patient on either tamoxifen or chemotherapy, leaving the impression that this will be the end of the problem.

It is toward the 8,000 women in all these studies who died, notwithstanding that adjuvant treatment, that this article is addressed. Moreover this article addresses the problem of reducing death from all other forms of solid malignant tumors.

What is proposed is adjuvant therapy with the combination of digitalis and coumarin congener drugs.

First to be discussed is adjuvant treatment with anticoagulants such as coumarin. The first of the coumarin-type anticoagulant was warfarin sodium that was first used in medicine about 1945. When we have a bleeding wound we need the formation of a blood clot to prevent death from bleeding. When we have the type of heart attack called myocardial infarction (MI), we often have a blood clot in a coronary artery that can cause death. We have in our blood small cells called platelets. In both of the above kinds of blood clots, first our platelets, due to their adhesiveness, form the first stage of a blood clot, a platelet or white thrombus. Then the platelet thrombus throws off clotting factors and a more massive fibrin or red thrombus forms on top of the platelet thrombus. The main portion of a blood clot is composed of fibrin. The coumarin type of anticoagulants tend to prevent the formation of the red or fibrin portion of a blood clot. Too much of one of these drugs will cause death fro m bleeding but a low safe dose can prevent the major portion of a coronary blood clot from forming while posing no risk to health.

In 1945, cardiologists reasoned that coronary blood clots were causing the vast majority of deaths from MI. From then on, for year upon year, patients who survived an episode of MI were anticoagulated with warfarin sodium or coumarin -type drugs. The same was true of stroke patients where the strokes had been caused by arterial blood clots. The concept behind this treatment was that these anticoagulants would prevent the formation of a second and perhaps fatal blood clot

In 1958 Professor R.A.Q. O'Meara of Trinity College in Dublin, Ireland had two papers in the Irish Journal of Medical Science,[ 1, 2] which it is here suggested were of epochal importance in cancer treatment. Few doctors read this Irish medical journal so their report went largely unnoticed. O'Meara reported that solid malignant tumors are coated with a jel of fibrin which he felt was vital to the tumor's ability to grow and metastasize, resulting in the ultimate death of the patient.

One doctor who did pay attention to O'Meara was L. Michaels of the Winnipeg General Hospital, Manitoba, Canada. He reasoned that if what O'Meara said was true, then there would be fewer cancer deaths among the millions of heart attack patients treated for years with anticoagulant drugs such as warfarin sodium or coumarin.

He did a study for a total of 1,569 patient years among patients maintained on anticoagulants between 1951 and 1963. His results, which were astounding, were published in The Lancet, October 17, 1964 issue. In all these patient years, there was not a single death from a cancer metastasis. There was only one cancer death in this large group whereas eight would have been expected. In this paper he gives four references to the fact that anticoagulants tend to reduce the ability of a primary tumor to grow and prosper and also that they tend to prevent metastases from forming.[ 3, 4, 5, 6] He also gave references dating back to 1903 showing that vascular blood clots induce metastases.[ 7, 8]

Between 1964 and 1981 medical literature has very little on the potential benefits of anticoagulants in cancer treatment. In 1981, there was a report from the VA Hospital at White Water Junction, Vermont on some success in treating small cell carcinoma of the lungs with warfarin sodium along with other treatment.[10] In 1983 Dvorak, Senger, and Dovrak of Beth Israel Hospital and Harvard Medical School had a long report on fibrin in malignant tumors in which they speculated on the possible benefits of anticoagulant therapy in cancer treatment. They gave compelling evidence that most malignant tumors are coated with a fibrin jel. They speculated that this fibrin jel fosters tumor growth in several ways. It acts as a barrier to prevent the body's immune cells from killing the cancer cells. It also acts as a barrier that holds within the tumor the antigens given off by tumors that marks them as being enemy or foreign. These are the antigens that could bring down the destructive force of o ur immune system on cancer cells. But most importantly, this fibrin jel seems to foster angiogenesis.[ 12]

Preventing angiogenesis may be a hidden white hope in both preventing and treating cancer. Judah Folkman of the Children's Hospital in Boston has been a lone voice in the wilderness, suggesting that the toxic and destructive therapies such as chemotherapy, and radiation with megavolt rays may not be needed in the prevention of and treatment of cancer, that cancer may be controlled by the simple control of angiogenesis. He first set forth his concept in the New England Journal of Medicine in 1971.[ 13] In the May 4th, 1989 issue of the same journal in an editorial, he said that his concept has now been widely accepted. His concept is as follows: All solid malignant tumors require angiogenesis to thrive and to form the metastases that are responsible for 90% of cancer deaths. Angiogenesis is the process by which new blood vessels are formed. According to Folkman, when a small cancer colony reaches the size of about 1,000,000 cancer cells, if this very small cancer cannot form by the processes of angiogenesis, a new system of blood vessels to feed and nourish the growing small cancer, then the small and harmless cancer will either withe r and die of starvation or remain a small, dormant and harmless cancer. It is his contention that if the complete inhibition of the process of angiogenesis can be achieved, it will follow that the first small harmless cancers can be prevented from ever growing into the large primary and secondary tumors that cause 90% of all cancer deaths.

Back to the Dvorac et al. paper,[ 12] these authors suggested that the fibrin jel, which coats nearly all solid malignant tumors, is a principle instigator of the process of angiogenesis. These authors made no mention of the 1964 Michaels paper but had they done so, they could well have concluded that in his report in 1964, what had happened to prevent a single death from a cancer metastasis in his large group was that the anticoagulants used had prevented the fibrin jel from forming on the small new metastases in his patients and that in the absence of the process of angiogenesis, no metastases were able to grow into a killing size.

One could say that the basis for the use of coumarin-type drugs in the adjuvant treatment of all types of solid malignant tumors is sheer speculation, but it is here suggested that the speculation is no greater than the speculation that resulted in the many trials of adjuvant chemotherapy and tamoxifen in the attempt to prevent recurring breast cancer.

So how benign would adjuvant coumarin therapy be to prevent cancer metastases and cancer recurrences in a broad spectrum of patients with solid malignant tumors? Between 1944 and 1970, millions of MI patients were anticoagulated for year upon year with coumarin-type anticoagulants. Three studies in this time frame showed little or no benefit of anticoagulants in preventing a second heart attack after a first one.[ 14, 15, 16] The potential danger in using these anticoagulants would be that overuse of them could cause internal bleeding. There was very little concern about internal bleeding by doctors who used these anticoagulants so freely in the period 1944 to 1970 and indeed, the record had shown very little in bleeding problems. Today doctors use these anticoagulants on a routine basis without concern in treating phlebitis.

As the use of anticoagulants was phased out in the 1970s, in treating MI patients, the use of the new beta-blocker drugs was phased in. However, in Holland in 1980 there was a large and highly successful test on coumarin-type anticoagulants in treating MI patients.[ 17] In this test in Holland a new test was used to determine the safe limit of anticoagulants that could be used, with the result that larger dosages of anticoagulants were used than had been used before. The results were better than any that had been obtained or would in the future be obtained, with the beta-blocking drugs. Over a two-year period, death among the anticoagulated patients was 7.6% as compared to 13.4% among the non -anticoagulated controls. Even with a higher dosage of anticoagulants than had been used before, bleeding episodes were not a significant problem.

This test came seven years after doctors had made up their collective minds to stop treating MI patients with anticoagulants. Beta-blocking drugs had replaced anticoagulants and there was to be no turning back. It is to be regretted that such was the case for rejecting or paying no attention to the excellent results of this Dutch test, doctors missed an opportunity to reduce deaths from cancer metastases. Like the Dvorac et al. paper, the doctors in this Dutch study also took no note of the great promise of the 1964 report by Michaels, and indeed they took no note as to what was happening with cancer metastases among their patients.

It is proposed that adjuvant coumarin therapy should be used in preventing cancer recurrence in patients with a broad spectrum of solid malignant tumors, at a safe dosage of about half the dosage used in this Dutch study.

On the use of digitalis in adjuvant cancer treatment, there is a communication to The Lancet in the May 19, 1984 issue on "Digitalis and Cancer." In this paper, a review had been done of hospital patients which indicated that cancer developed less often in patients who took digitalis. It was also noted that digitalis is toxic to HeLa cells.[ 18] HeLa cells are a highly malignant line of ovarian cancer cells that came from a woman by the name of Henrietta Lack who died in the 1950's. Her cancer cells live on in tissue cultures. Any substance that is toxic to HeLa cells is presumed to have some anti-cancer activity.

There was a greatly exciting report in the February 25, 1982 issue of the New England Journal of Medicine from Sweden. In this study it was found that recurrence and death from breast cancer was 9.6 times more frequent among women NOT taking digitalis. It was also noted that breast cancer cells are smaller and that the disease is less aggressive in women taking digitalis.

Digitalis is estrogen-like and no doubt benefits patients by binding estrogen receptors. For nearly 200 years digitalis was the leaf of the foxglove. Now leaf digitalis has been replaced by synthetic digoxin and digitoxin which has the glycoside from the foxglove leaf. Digitoxin most likely is the form of digitalis that should be used in treating cancer.

It has now been shown that tamoxifen causes endometrial cancer to about the same degree as it prevents recurring breast cancer.[ 9] A woman over 50 can take but little satisfaction in being told that if she takes tamoxifen for two years, her chance of dying of recurring breast cancer will be reduced by one-fifth while her chance of developing endometrial cancer will increase to the same degree.

No one offers a lung cancer patient any form of adjuvant treatment. It is to be hoped that doctors may read this proposal and want to use low safe doses of both digitalis and coumarin-type drugs in the adjuvant treatment of all types of solid malignant tumors. Both digitalis and coumarin-type drugs are inexpensive and at half the therapeutic dosages, may be presumed to be harmless.

There is much evidence that the combination of low doses of digitalis and coumarin-type drugs as adjuvant therapy will work far better for all types of solid malignant tumors than are adjuvant tamoxifen and chemotherapy, in preventing recurring breast cancer. To repeat, in the 1964 study by Michaels, in a large group maintained on anticoagulants, there was not a single death from cancer metastases and only 1/8th the expected cancer deaths, and in the 1982 Swedish study there was almost a 90% reduction in recurring breast cancer among women taking digitalis.

It would also be helpful in reducing cancer deaths if all patients would practice iron restriction. In the New England Journal of Medicine for October 20, 1988 is a report on "Body Iron Stores and the Risk of Cancer." In this study among 14,000 adults, it was found that there was a decided increase in the risk of cancer deaths among men who had higher levels of body stored iron. It was concluded that the same situation seemed to prevail among women but that more study was needed.

In my paper in Medical Hypotheses for January 1984, I tell of the situation that prevailed in Africa prior to 1923. In the British Medical Journal in June and July of that year is a series of letters on the subject of the freedom from cancer among African natives who lived out of contact with Europeans. One doctor who had spent many years in Nigeria wrote about the freedom from cancer among the natives there. This prompted other letters from other doctors in various parts of Africa taking note of the freedom from cancer among natives in all parts of Africa.[ 19, 20, 21, 22] Albert Schweitzer took note of the freedom from cancer in 1913 among the natives when he established his hospital at Lambar&eacute]n[é in Gabon.[ 23] There may have been other reasons for the freedom from cancer among these African natives but they were strict vegetarians with a very low iron intake.

In 1982 Maria de Sousa, then at the Sloan-Kettering Institute for Cancer Research, showed that high body iron stores are highly immunosuppressive. Anything that is immunosuppressive can and does cause cancer. She suggested that one way to treat cancer was by iron withholding.[24]

Most bacterial infections thrive by using body stores of iron. Helen Nauts in her Monograph No. 8, Cancer Research Institute, has reviewed 449 cases over the past 150 years where far advanced cancer patients were stricken with bacterial infections, and having survived the bacterial infections were cured of cancer. In part she attributed these remarkable regressions to the fact that the bacterial infections depleted the body's iron stores and that with immunosuppressive iron depleted, the body's immune system was able to attack and kill all cancer cells. Another thought along this line is that in pre-antibiotic days, patients survived bacterial infections in the same manner. As the body's iron stores were depleted by the bacterial infection, the body's immune system was activated and was able to rid the body of the bacteria causing the infection.

One adjuvant treatment of all forms of cancer would be to reduce iron intake. Red meat is rich in iron and in the USA all bread and most breakfast cereals have added iron. Most vitamin pills contain iron. Cancer patients would do well to turn vegetarian and otherwise avoid iron.

Breast cancer patients would do well to avoid sugar like a plague. Horrobin and Seely had in the July 1983 issue of Medical Hypotheses a paper with the title "Diet and Breast Cancer: the Possible Connection with Sugar Consumption." In this report it was shown that worldwide, among women over 50, breast cancer is proportional to sugar consumption. As examples, England has the highest sugar consumption of any nation in the world and at the same time the highest breast cancer death rate. The English figures are 145 grams of sugar consumption per day and among women aged 65-74, 122 breast cancer deaths per year per 100,000. In Greece the figures are 52 grams of sugar per day and 52 breast cancer deaths per 100,000.

When one eats sugar, one's body produces insulin and insulin may be as potent as is estrogen in inducing breast cancer. Indeed in the USA among women over age 50, a high consumption of sugar may be causing more breast cancer than is estrogen. Among younger women in the Horrobin/Seely study the same relationship between sugar consumption and breast cancer deaths existed but to a lessor extent, the reason no doubt being that younger women produce more estrogen and with them a greater portion of breast cancers may be estrogen -induced.

The use of a combination of iron restriction, sugar restriction and adjuvant therapy in the treatment of all solid malignant tumors with low doses of digitoxin and a coumarin-type drug could well lead to a 50% reduction in cancer deaths.

Correspondence:

Wayne Martin

25 Orchard Drive

Fairhope, AL 36532

References
1. O'Meara RAQ Jackson R.D: Cytological observations on carcinoma. Irish Journal of Medical Science (6): 327-328, 1958.

2. O'Meara RAQ: Coagulative properties of Cancers. Irish Journal of Medical Science (6): 474-479, 1958.

3. Wood, S., Jr. (1958) Arch. Path. 66 550.

4. Lacour, F. et al., Bull Assn. Franc. Cancer, 44:88.

5. Wood, S. Jr. et al., (1956) Proc. Amer. Assn. Cancer Res. 2:157.

6. Cliffton, E.E, Agostino, D. (1962)Cancer(Philad.), 15:276.

7. Iwasaki, T. (1915) J. Path. Bact. 20:85.

8. Schmidt, M.D. (1903) cited by Iwasaki, T. (1915) J. Path. Bact. 20:85.

9. Fornander, T. et al., Adjuvant tamoxifen in early breast cancer: occurrence of new primary cancers. Lancet Jan. 21, 1989, pp 117-19.

11. Zacharski L.R. et al., Effect of warfarin on survival in small cell carcinoma of the lung. JAMA (245): 832-835, 1981.

12. Dvorak, Harold, Senger, Donald R., and Dvorak, Ann, Cancer Metastases Reviews 2:41-73, 1983 Martinus Nijhoff Publishers. Printed in the Netherlands.

13. Folkman, J. Tumor angiogenesis: therapeutic implications. New England J. of Medicine: 285:1182-6.

14. Wright, I.S. et al., American Heart Journal, 36: 801 (1948).

15. JAMA 189:183 (1964)

16. JAMA 225:724 (1973).

17. deVries, W.A. et al., A double-blind trial to assess long term oral anticoagulant therapy in elderly patients after myocardial infarction. Lancet 8 Nov. 1980 pp 989-993.

18. Shiratori, Y. et al., Growth inhibitory effect of cardiac glycosides and aglycones on neoplastic cells. Gann (1967) 58: 521.

19. Fouché, F.P. Freedom of the negro races from cancer. British Medical Journal, June 30, 1923, p 1116.

20. Hollander, Bernard. Freedom of the negro races from cancer. British Medical Journal, July 7, 1923.

21. Sharp, N. Dyce. Freedom of the negro races from cancer. British Medical Journal, July 14, 1923.

22. Blair, M.C. Freedom of the negro races from cancer. British Medical Journal, July 21, 1923.

23. Schweitzer, Albert. On the Edge of the Primeval Forest (MacMillan) 1931.

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By Wayne Martin

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