The Use of Suramin in the Treatment of
Hormone-Refractory Prostate Cancer
Last Revised January 6, 1996
[Note: developments since this was written may change the information.]
Introduction |
The questions that have been answered |
The predicted clinical uses |
Adverse reactions to suramin |
Concluding remarks
Introduction
The use of suramin as a drug for the treatment of parasitic infestations
dates back to the early years of the 20th Century. Although it was an
effective form of treatment, it was also associated with a significant
number of well recognized but potentially severe side effects and the
added drawback that it has
to be given intravenously. (It is not available in an oral formulation.)
Recent interest in the activity of suramin as a form of therapy for patients
with advanced prostate cancer resulted from investigation of suramin as a
promising compound for the treatment of patients with acquired immunodeficiency
syndrome (AIDS). Although suramin was found to have no clinical value in the
management of patients with AIDS, it was noted suramin appeared to induce
adrenal insufficiency and that it appeared to have effects on growth factors
involved in prostate cancer cell growth.
Extensive studies have now been carried out to improve our understanding
of the mechanisms of action of suramin and how we can avoid the serious
side effects which have been commonly observed in the past. The Prostate
Cancer InfoLink does not intend to provide a detailed analysis of this information.
Rather, for patients and interested health professionals, it is perhaps more
important to understand the potential uses for this product based on
the expected results of clinical trials which are nearing completion and
publication.
The questions that have been answered
One of the first questions that had to be answered regarding the use of
suramin in the treatment of advanced prostate cancer was whether researchers
could find an appropriate and useful dose of the drug which produced
effective clinical responses in patients with a minimum level of adverse reactions.
Two basic approaches have been taken to this question. The first approach has
assumed that drug levels of suramin must be titrated (managed) on a patient
by patient basis or that a dosing schedule could be developed which
would maintain plasma levels of suramin between acceptable levels to provide
therapeutic efficacy without risk of serious adverse reactions. The second approach
was to seek a standard therapeutic dose of suramin which would be clinically
effective and safe in the vast majority of patients. These studies are
still going on. However, it appears that both approaches may
be successful. One large clinical trial has now been completed which was
designed to evaluate the relative value of suramin at three different doses
(600, 1000, and 1400 mg/m2 per day. Other studies have shown that
it is possible to maintain certain plasma concentrations of suramin. Clearly,
it would be easier if it was possible to determine a specific dose of suramin
that was effective and safe for the majority of patients.
A second question that has had to be addressed is the necessity for adjuvant
therapy with glucocorticoids and mineralocorticoids (different classes of
corticosteroids). Because suramin clearly induces adrenal insufficiency in
the majority of patients, it now appears probable that patients receiving
suramin will certainly need adjuvant therapy with low-dose hydrocortisone and
possibly with other agents.
The predicted clinical uses of suramin
Clinical researchers are currently awaiting the results of two major
randomized prospective trials
designed to evaluate the potential future uses of suramin.
The first of these two trials has been designed to test the use of suramin +
hydrocortisone in the treatment of patients failing combined hormonal therapy.
This has always been the setting in which most clinicians felt that suramin
was most likely to have clinical value if an appropriate dose could be established.
The second trial has been designed to test the use of suramin + hydrocortisone
in the treatment of patients with stage M+ (stage D2) prostate cancer who have
never received hormonal therapy of any type. This trial will only
provide us with useful information if it compares this form of therapy to
complete hormonal therapy in a comparable patient group.
Adverse reactions to suramin
Under no circumstances should patients or health professionals overlook the
fact that historically suramin has been associated with a series of potentially
serious side effects. These side effects appear to be closely correlated with
the plasma levels of suramin in individual patients.
Although recent studies have allowed clinicians to significantly reduce the
incidence of severe side effects, suramin has been associated with dose-limiting
malaise and fatigue,
coagulopathies, sensory and motor neurotoxicities, parasthesias, neutropenia, anemia,
lymphopenia, thrombocytopenia, and a whole range of other adverse reactions.
The incidence of these adverse reactions in randomized clinical trials will be
important to our understanding of the potential uses of this drug.
Concluding remarks
The Prostate Cancer InfoLink expects to see publication of the results of
randomized clinical trials of suramin in different patient populations in
1996 and 1997. Whether these trials will definitively indicate a place for
suramin in the treatment of some patients with advanced prostate cancer is
still open to question. Information received by The Prostate Cancer InfoLink
has suggested that suramin may offer a significant survival benefit in some
patient groups. However, as yet there is no published data to support this
preliminary information.
It seems very probable to The Prostate Cancer InfoLink that suramin will
indeed prove to be a drug which can induce significant clinical responses
in some patients with prostate cancer. The question is going to be
whether the risk of adverse reactions associated with suramin can be
managed down to a sufficiently low level that the possibility of effective
treatment is associated with a high probability of successful outcome
outside very carefully controlled clinical trials.
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