This is about the anti-cancer effect of dipyridamole.
It is a harmless widely-used drug in treating patients who have survived
an episode of thrombotic stroke or coronary thrombosis, that has a vast
potential of being a harmless anti-cancer drug.
First let us look at the report in The Lancet
in the March 23, 1985 issue, p. 693, by E.H. Rhodes et al. of St. Hileir
and Kingman Hospital in Surrey, England. These doctors for the past
11 years had been maintaining melanoma patients with ClarkÕs
level IV and III disease on dipyridamole, 300 mg a day. Thirty of these
patients were maintained on this dose of dipyridamole. Of them, 26 had
level IV disease and four had level III disease. At five years, the
survival of the level IV patients was 74%. The five-year survival for
the total of the 30 of level IV and III disease was 77%. None of the
level III patients died. Reference was given that the expected five-year
survival for level IV melanoma is 32%. In the case of melanoma, 100%
of deaths are caused by distant metastases. Reference was given that
when metastases in many forms of solid malignant tumors are formed from
the vascular network, the tumor cells moving in the blood circulation,
at the beginning of metastasis formation, are attached to the vascular
endothelium. Reference is also given that dipyridamole tends to prevent
this attachment of cancer cells flowing in the blood circulation to
the endothelium and thus tends to prevent the formation of metastases.
Dipyridamole, like aspirin, inhibits platelet adhesion,
and thus tends to prevent the vascular thrombosis of heart attacks and
strokes. In the Lancet in the December 12, 1987 issue (pp. 1,371-4)
was the report of the European Stroke Prevention Study. The introduction
to this report reviewed the indicated lack of benefit in treating with
aspirin, patients who had survived a small stroke, a TIA, a temporary
ischemic attack. In this trial, dipyridamole 300 mg a day was added
to treatment with aspirin and the results were outstanding. Over a two-year
period, stroke deaths were decreased by 50%, deaths from myocardial
infarction decreased by 38% and deaths from cancer by 25%.
The numbers of patients involved were small, however
here is another indication of an anti-cancer effect of dipyridamole.
I have had a long exchange with Dr. Betty Rhodes
who has been in retirement for about eight years. She treated melanoma
with dipyridamole because she is a dermatologist and that is the kind
of cancer that she treated. She has been disappointed that there has
been no followup on this most hopeful indication that she has demonstrated
of dipyridamole in treating melanoma. She feels that dipyridamole may
be just as effective in treating many other forms of solid malignant
The above-indicated anti-cancer effect of dipyridamole
may be due only to its prevention of metastases, however Eva Bestida
et al. of the University of Barcelona had a report in Cancer Research
in the September 1985 issue (pp. 4,048-4,062) on the inhibition of certain
human cancer cell growths by dipyridamole. It caused an inhibition of
greater than 80% of adinosine, thymidine and uridine. These are substances
needed by cancer cells to prosper. This may indicate an anti-cancer
effect of dipyridamole other than in the prevention of metastases.
In 1958, Professor R.A.Q. OÕMeara of Trinity
College, Dublin Ireland, had a report on Coagulation and Cancer in the
Irish Journal of Medical Science, vol. 394, pp. 474-9. I met
with him briefly in 1965. At that time he felt that with both the primary
tumor or a metastasis, clotting factors are given off by cancer cells
and then cancer cells tend to become coated with fibrin. He felt that
our cancer cell-killing immunocytes can kill cancer cells more effectively
if they can make contact with cancer cells. He felt that this fibrin
coat on cancer cells acts as a protective barrier to prevent them from
being killed by immune attack.
I think that L. Michaels may have been one of OÕMearaÕs
students. In any event Michaels had a report in The Lancet in
the October 17, 1964 issue (pp. 832-5) with the title ÒCancer
Incidence and MortalityÓ in patients having Anticoagulant Therapy.
In that time frame nearly every patient who had survived a heart attack
or a thrombotic stroke was maintained for year after year on warfarin.
The concept was that warfarin would prevent the formation of the red
or fibrin thrombus. Michaels did a study of such patients to the extent
of over 1,500 patient years. There was among them only one death Ð
that of a primary lung cancer when in this group eight cancer deaths
had been expected.
Warfarin will tend to prevent the red or fibrin
part of a blood clot. Dipyridamole, by preventing the formation of the
white or platelet thrombus, will also be preventing the formation of
a fibrin thrombus.
The tendency of cancer cells to give off clotting
factors puts cancer patients at a far greater risk of death from vascular
thrombosis. They are greatly more at risk of death from a heart attack
In 1958 at the time of the first OÕMeara
report, there was very little thought being given to the role of platelets
in heart attacks and thrombotic strokes. Beginning in 1945, the standard
treatment for survivors of heart attacks or thrombotic strokes was to
anticoagulate with warfarin or similar anticoagulating drugs. By 1970
the practice had almost completely come to an end. It was decided that
anticoagulant treatment was not increasing survival. By then it was
understood that in the vascular tree, there will never be the formation
of a red or fibrin thrombus without there first being a white or platelet
thrombus. The discovery of the factors in the arachidonic acid cascade
and of the platelet aggregation substance thromboxane A2 was the basis
for the Nobel Award for Medicine in 1982. It then followed that a platelet
thrombus with no fibrin thrombus could be enough of an occlusion to
cause a thrombotic stroke or a heart attack.
With this understanding, along with the knowledge
that aspirin will tend to reduce the aggregation of platelets, the entire
medical establishment replaced warfarin with aspirin in treating heart
attacks and thrombotic strokes.
Since that time there have been three trials in
England in using aspirin in the prevention of a heart attack and two
in the USA. Of these five trials only one, the Physicians Health Study
in the USA showed any benefit at all. This one trial that did show some
benefit in the prevention of a heart attack used Bufferin and Bufferin
contains aspirin and magnesium.
There are many reasons to believe that dipyridamole
at 300 mg a day will be far more effective in the prevention of heart
attacks and strokes than aspirin. Moreover dipyridamole has none of
the harmful side effects of aspirin.
As of March 1999, there is now a new light thrown
on the harm of platelet aggregation, this time with respect to cancer.
In Cancer Research March 1999, pp. 1295-3000, B. Nieswandt et
al. of the University of Regensburg, Germany had a report on platelet
aggregation and cancer. Using three different tumor cell lines in mice,
it was demonstrated that tumor cells can activate platelet aggregation
and that platelet aggregates deactivates cytotoxic NK cells, preventing
NK cells from killing cancer cells.
This is to suggest that dipyridamole is a harmless
drug. The generic form of it costs less than one dollar a day for treatment.
It has in one small trial been demonstrated that it is effective against
melanoma. There is every reason to feel that it may be effective against
a broad spectrum of cancers.
If it were granted that all cancer patients are
at a greater risk of heart attacks and strokes, it is hoped that many
doctors will treat cancer patients with dipyridamole for this reason.
However if they do so, it will soon be found that dipyridamole will
be having a marked anti-cancer effect.
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