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CHAPTER XII
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PHASE II STUDY OF MULTIFORM
GLIOBLASTOMA |
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SURVIVAL OF PATIENTS WITH
GRADES Ill AND IV ASTROCYTOMA
(GLIOBLASTOMA MULTIFORM) USING
AMYGDALIN
PHASE II STUDY
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Dr. Ernesto Contreras Rodriguez,
M.D.
Dr. Salvador Rubio Veliz, M.D.
Dr. Jose Ernesto Contreras
Pulido, M.D.
Medical Personnel of the
Hospital y Centro Medico Del Mar
Playas de Tijuana, B.C.N, Mexico
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Summary
Nineteen patients with
histopathologically proven persistent Grades
Ill and IV Glioblastoma following surgery
and/or radiotherapy, were treated with
AMYGDALIN for a minimum of six weeks. The 12
months survival from the time of diagnosis
was 21% and 19% from the initial AMYGDALIN
treatment. The median survival was seven
months from diagnosis and five months from
the initial usage of AMYGDALIN. It is
suggested that AMYGDALIN increases the life
expectancy of these patients when used
sequentially to conventional therapy or as a
third alternative in those patients with
failure to the latter. It is mentioned that
there is also subjective improvement in
patients with Glioblastoma Multiform who are
exposed to AMYGDALIN.
GLIOBLASTOMA MULTIFORM
/ AMYGDALIN I PHASE II STUDY
Introduction
The frequency for neoplasms of the Central
Nervous System in the USA and other highly
industrialized countries varies between 3.8
and 5.1 per 1,000 inhabitants. Approximately
1.7% of the diagnosed neoplasms and 2% of
the deaths from cancer correspond to
patients with neoplasms of the C.N.S.
Although these neoplasms can be found at any
age, they are most frequent in the sixth and
seventh decades of life, and females are
slightly more frequently affected than
males.
The
majority of cerebral tumors are
histologically benign, but approximately 25%
correspond to Glioblastomas Multiform. These
neoplasms include 54% of all
Gliomas and their prognosis oscillates
between a median survival of 4.5 months from
the initial diagnostic craneotorny. Survival
to 18 months is scarcely 18%.
Up to now
there is no cure and the best results are
obtained after surgical resection
(frequently in complete) and/or
radiotherapy.
The
palliative value of this treatment is beyond
question because of the improvement in the
quality of life (subjective and objective)
which the patients experience, as well as,
in the significant, statistical in crease of
their survival.
Until the
advent of the nitrous agents, there had not
been found any chemotherapeutic agents that
were successful in the treatment of
cerebrial neoplasms and even now, it is
continuing to be accepted that the value of
chemotherapy against these tumors is very
limited, although sporadically some
heartenng results in selected patients are
reported.
All this
has been explained by the so-called
blood-brain barrier which, although it does
not have an anatomical explanation, is
indeed a well documented physiological
discovery. Many medicines, including the
majority of the antineoplastic agents,do not
achieve therapeutic levels in the cerebral
tissues.
This all shows the urgency of the search for
new methods of palliative treatment for
these patients with fatal or short-term
prognosis.
Patients and-Methods
With the purpose of analyzing the value of
AMYGDALIN in patients with Grades Ill-IV
Astrocytoma (Glioblastoma Multiform), a
retrospective study was performed on the
evolution of all the patients who had
entered the Centro Medico Del Mar with
histopathotogical confirmation of
Glioblastoma Multiform between Jan. 1, 1975,
and Dec. 31, 1979, and had received a
minimum of six weeks of treatment with
AMYGDALIN with the schedule shown in Chart
1.
All
patients had a complete, clinical history
and specialized, neurologic examination,
hematic biometry, blood work (computerized
analysis of 12 to 23 tests), urinalysis, P-A
and lateral chest and head x-ray studies. In
some patients the study was complemented
with a brain scan, CAT scan of the brain, or
other specialized study. Follow-up was
individualized.
Survival
was determined to be twelve months and the
average survival figured from the time of
diagnosis as well as from the first dose of
AMYGDALIN compared to that reported in world
literature.
Results
Nineteen patients were included: eight males
and eleven females. The average age was 47;
the youngest, 27, and the oldest, 65.
All of the
patients had submitted to partial, ablative
surgery and complementary radiotherapy. The
majority had clinical history of tumoral
persistence but this was not confirmed
radiographically in all cases.
The survival
of twelve months, from diagnosis, was 21%
(four out of nineteen patients) and 19%
from the first application of AMYGDALIN (two
out of nineteen patients). The median
survival was seven months from diagnosis and
five months from starting treatment with
AMYGDALIN.
Comment
Upon comparing these figures with those from
world reports, we can conclude that the
sequential use of AMYGDALIN following
surgery and radiotherapy, in the treatment
of Glioblastoma Multiform, appears to
increase survival to twelve months in a
Substantial number of patients, and the
overall average survival of these patients
from the time of diagnosis. In addition, we
conclude that the use of AMYGDALIN as the
sole treatment for those patients with
failure to respond to conventional therapy,
because of persistent or tumoral recurrence,
seems to offer survival of twelve months and
increased average sur vival from the initial
application of AMYGDALIN, at least equal to
that offered by conventional treatment for
the untreated patient.
This becomes
more significant if one takes into account
that the patients who fail to respond to
conventional treatment generally have a
short-term survival.
Subjective Response
We should mention that although not
documented statistically, it was observed
that the patients with Glioblastoma
Multiform who received AMYGDALIN experienced
subjective improvement greater than that
expected with only symptomatic treatment.
We believe
that other studies with a larger number of
patients must be completed before drawing
definite conclusions, but with this Phase II
study, one can mention as a valid conclusion
that AMYGDALIN demonstrated a clear,
antineoplastic effect in patients with
Glioblastoma Multiform which was persistent
or recurrent to conventional treatment.
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Chart 1.
Treatment
Schedule with AMYGDALIN
Used for Patients with Glioblastoma
Multiform |
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Initial Phase (Six
Weeks): |
AMYGDALIN 6 g, LV,
per day, 6 days per
week for 3 weeks.
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Subsequent Phase:
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AMYGDALIN 6 g, LV.,
1-3 days per week
AMYGDALIN 1-2 g,
orally, the
remaining days.
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CLARIFYING NOTES
This study was performed under
the sponsorship of KEMSA LABS of
Playas de Tijuana, B.C.N,,
Mexico.
In this study KEMDALIN-S 1100%
pure AMYGDALIN in injectable
solution of 3 mg/ml of acqueous
solution) was used.
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