Are Heart Drugs Better for the Treatment of Cancer

Digitalis is the right drug being used to treat the wrong disease.
Wayne Martin.

Introduction

Several different types of drug, used or developed for the treatment of heart disease, have been found to have dramatic beneficial effects on a wide range of cancers.

Digitalis

Extracts of the foxglove have been documented in folk remedies for a number of conditions and for hundreds of years. Since William Withering published his book, An Account of the Foxglove and Some of its Medical Uses , in 1785, digitalis has been used by conventional medicine in the treatment of cardiac congestion and some cardiac arrhythmias.

As a student at Purdue University in 1930, Wayne Martin had as a tutor a seventy-year old medical doctor who had lost his money in the 1929 stock market crash and had taken a $60.00 a month instructorship at the university. Using the files of the Indiana University School of Medicine this doctor had done a survey between 1900 and 1930 of patients maintained on digitalis for life (digitalis was then used for heart patients). What he found was that not one of them had died of cancer. He was unable to get his survey published. At Purdue, Wayne says, the staff thought him to be suffering from dementia and he soon learned that if he wanted to keep his instructorship it was best not to talk about digitalis and cancer. ⁽¹⁾

In 1974, Dr Bjorn Stenkvist of University Hospital, Uppsala, Sweden, made application to the United States National Cancer Institutes for funds to conduct a clinical trial of the therapeutic effects of digitalis in breast cancer. The funds were granted, the study done. In 1980, they found that tumours in patients on digitalis medication at the time of diagnosis of breast cancer seemed to develop much more slowly than tumours in patients not on such medication. ⁽²⁾ and the results, published in 1982, ⁽³⁾ were not just good, they were astounding. In this study forty-four breast cancer patients were maintained on digitalis from the time of surgery fro five years. Among them there was only one recurrence of cancer. The trial's control group consisted of eighty-eight breast cancer patients who were not taking digitalis. In this group there were twenty-one recurrences of cancer - 9.6 times as many. In other words, the digitalis reduced cancers by almost ninety percent.

In 1984 Drs A G Goldin and A R Safa, of the National Cancer Institutes (NCI), Bethesda, Maryland confirmed Stengkvist's results. Conducting a retrospective study of 127 cancer patients in their records, of a total of twenty-one deaths they found only one cancer death among those who had taken digitalis. ⁽⁴⁾

For many years Martin was surprised that there was no follow-up to Stenkvist's most promising trial, particularly as it had NCI support. In the mid-1990s Dr Johan Haux of the Institute of Cancer Research and Molecular Biology at the University of Trondheim, Norway, had shown an interest in Coley's Toxins and Martin had had a correspondence with Haux on this subject. Martin asked Haux if he could find Dr Stenkvist which he did. Dr Stenkvist was in retirement. However, he reported that the Chief oncologist at University Hospital at the time took no interest in his work and he, Stenkvist, had been unable to interest any pharmaceutical firm in a cancer treatment on which they could not get a patent and which sold for fifteen cents a day.

At that time Haux was looking for a subject for his PhD thesis. In May 1997 Martin sent Haux the digitalis story and suggested he pursue it. Haux started his work with two breast cancer cell lines, one oestrogen positive and one oestrogen negative. Using highly sophisticated testing methods, he treated these two cultures with digitoxin, the natural form of digitalis from the common foxglove ( Digitalis purpurea ), and in six days preparations used are digitoxin, and digoxin, saw an almost complete inhibition of growth of these two breast cancer cell lines. He determined that this inhibition was due to apoptosis (cell death). Haux also tested the more widely used digoxin, a preparation from the white foxglove ( Digitalis lanata ) the drug of choice in Britain and the USA today. This had very little anti-cancer effect. (In the Stenkvist report of 1982 one third of his patients were getting digitoxin, the other two thirds were getting digoxin. In the NCI letter of 1984 there was a cancer death in the patients taking digitalis but by then the vast majority of patients taking digitalis were getting digoxin.)

Haux then grew cultures of malignant human T cell line Jurkat and B lymphoblastoid cell line Daudi These cancer cell lines were inhibited to an even greater extent than the breast cancer cell lines, again by apoptosis. Digoxin was even less effective. Digitoxin and digoxin were also tested against a fifth cell line, K562, and against normal cells. With these there was no effect.

Haux sent his first report to the medical journal, Cancer Research . It was rejected. The first reaction from conventional medicine to the suggestion that digitoxin could be an anti-cancer drug was "ridiculous". He then sent it to the British Journal of Cancer . In this submission Haux only claimed that in a harmless concentration to humans, digitoxin will inhibit Jurkat cells. Again it was refused. The study was finally published in 1999 in the Journal of Oncology . ⁽⁵⁾

The hospital where Haux worked were using a chemotherapeutic drug, Actinomycin D in treating cancer at the hospital. The belief is that if an anti-cancer drug will inhibit the Jurkat cell line, it has a bright future. Haux did a test that got the attention of the management at the Trondheim hospital. Haux tested Actinomycin D against his Jurkat cell line at a concentration used to treat cancer patients. It had almost no inhibitory effect at all. In September 1997 a decision was taken at Trondheim to begin treating breast cancer patients with digitoxin.

In a subsequent study, Haux tested digitoxin and digoxin against three brain cancer (glioblastoma) cell lines with similar results to his other trials. ⁽⁶⁾ He is currently studying whether the cancer rate is changed in a cohort of 8,000 cardiac patients on digitoxin compared with controls.

Encouraged by Hauk's research, Stenkvist conducted a long-term follow-up (22.3 years) of 175 of his previous patients with breast carcinoma, of which 32 were on digitalis treatment when their breast cancer was diagnosed. He found only two (six percent) of the thirty-two patients on digitalis had died from breast cancer compared to forty-nine (thirty-four percent) of the patients not on digitalis. Stenkvist says that although the few deaths in the digitalis group made statistical analysis difficult, nevertheless, "serious consideration should be given to the effects of digitalis derivatives on cancer cells in cancer drug design. This field of research is not sufficiently explored and holds promise to contain drugs superior to present-day adjuvant therapy both with respect to effects and side-effects". ⁽⁷⁾

Hawthorn

In the 1920s there were many doctors using an extract of the hawthorn berry for treating what was then called 'dropsy'.They were nearly all put out for business by 1926. The medical journal, Medical World , fostered unorthodox modalities. It carried a report in 1930 about how the glycoside in the hawthorn berry was much like digitalis. It also said that, unlike digitalis, the hawthorn glycoside was not toxic in an overdose. Thus it may be worthwhile studying the anti-cancer effects of hawthorn too.

Anticoagulation drugs

Cancers which do not spread are called 'benign' and generally not considered particularly dangerous. It is the 'malignant' ones which metastasise (spread) which are the killers, for once a cancer has metastasised, conventional medicine has no effective remedy. It is vital, therefore, that once a cancer has been discovered, it is not allowed to metastasise. Fortunately, there seems to be a simple way to stop, or at least inhibit, a cancer's spread. That is the use of an anticoagulation drug such as warfarin or heparin. These are cheap, generic drugs routinely used in cases of heart attack and blood clots (thromboembolism).

It was demonstrated as long ago as 1903 that distant metastases from cancer cells circulating in the bloodstream couldn't end up just anywhere, that for a distant tumour to form, it needed a thrombus (clot) at the site of the metastasis to be. ⁽⁸⁾ This was confirmed in 1915 ⁽⁹⁾ and 1956 ⁽¹⁰⁾ . In 1956 and 1957 ⁽¹¹⁾ two groups of scientists also demonstrated independently that anticoagulants inhibited local tumour growth.

In 1958 Professor R A Q O'Meara of Trinity College, Dublin, showed that dividing cancer cells were surrounded by fibrils which gave off clotting factors just as platelets do, causing the deposition of fibrin. ⁽¹²⁾ He suggested that this was essential for tumour growth. In this way, he taught, a cancer colony becomes coated with fibrin which prevents cancer cell killing immunocytes from making contact with and killing it. When Martin met him in 1966, O'Meara had expanded his hypothesis in line with Schmidt and was teaching that a cancer cell travelling in the bloodstream could not form a distant metastasis without there being a small fibrin clot at the site of the metastasis to be.

O'Meara had a student, L Michaels, who when qualified went to Canada. In 1960, nearly all patients who had survived a heart attack or a thrombotic stroke were being anticoagulated for year on year with warfarin or other anticoagulation drug. These drugs prevented the formation of fibrin. Michaels reasoned that if O'Meara was right, then there should be far fewer cancer deaths among the several million anticoagulated population. So Michaels did a 1,500 patient-year study of these patients. ⁽¹³⁾ What he found was that they had only one-eighth the expected numbers of cancer deaths. He also found that in his study population there was not a single death from a metastasis. There was only one death and that was from primary lung cancer. Among the study group were two breast cancer patients. Neither developed metastases.

Streptokinase - the clot (and cancer) buster

When a person has a heart attack one of the first things that is done on his reaching hospital is an infusion of a fibrinolytic (clot-busting) drug, streptokinase. This is to break down any clot that may be blocking a coronary artery.

Professor Leo Zacharski, Department of Medicine, Dartmouth Medical School, Lebanon, New Hampshire, has researched anticoagulant drugs extensively. He talks of a spectacular case of a woman who had widely metastatic endometrial cancer. She was already in a very bad way when she suffered a heart attack which may actually have saved her life. Because of the heart attack she was given streptokinase. "One week later" says Zacharski, "her tumor showed marked regression which has persisted for many months". ⁽¹⁴⁾

Professor Zacharski wrote a comprehensive review of anticoagulant drugs in The Cancer Journal - Volume 6, Number 1 (January-February 1993).

Conclusion

Many, if not all, of the drugs used to prevent or control heart attacks have a long history of efficacy in the fight against cancer. Despite this few, if any, are used for this purpose. The problem, I believe, is that the clinical trials required by regulatory bodies today before any drug can be licensed for use are so costly that no drug company, with no chance of a patent on the drug, would be willing to sponsor such a trial. It is left, therefore, for the cancer patient to hope that he or she develops heart problems along with the cancer so that he/she gets the better treatment than oncologists offer.

References

1. Martin W. Personal communication, 1997.
2. Stenkvist B, et al. Evidence of a modifying influence of heart glucosides on the development of breast cancer. Anal Quant Cytol 1980; 2: 49-54.
3. Stenkvist B, et al. Cardiac glycosides and breast cancer, revisited. N Engl J Med 1982; 306:484.
4. Goldin AG, Safa AR. Digitalis and cancer. Lancet 1984;1:1134.
5. Haux J, et al. Digitoxin, in non toxic concentrations, induces apoptotic cell death in Jurkat T cells in vitro. Germ J Oncol 1999; 31: 14-20.
6. Haux J. Digitoxin is a potential anticancer agent for several types of cancer. Med Hyp 1999; 53: 543-8
7. Stenkvist B. Is digitalis a therapy for breast carcinoma? Oncol Rep 1999; 6: 493-6.
8. Schmidt MB. Cited by Iwasaki T. J Path Bact 1915; 20: 85.
9. Iwasaki T. J Path Bact 1915; 20: 85.
10. Wood S jr, Holyoke ED, Yardley JH. Proc Am Assn Cancer Res 1956; 2: 157.
11. Lacour F, Oberling CH, Guerin M. Bull Assn Franç Cancer 1957; 44: 88.
12. O'Meara RAQ. The coagulative properties of cancer. Irish J Med 1958; 394: 474-9.
13. Michaels L. Cancer incidence and mortality in patients having anticoagulant therapy. Lancet 1964; ii: 832-5.
14. Leo R Zacharski. Fax to Wayne Martin, 7 February 1994.

Last updated18 December 2000