The Management of
Hormone-Refractory Prostate Cancer:
An Overview
Last Revised March 18, 1996
[Note: Treatment may have evolved since this was written. For education only.]
Introduction |
Warning to patients |
First considerations |
Secondary forms of hormonal therapy |
Radiation therapy |
Suramin therapy |
Chemotherapy |
Newer experimental approaches
Introduction
Many women who have breast cancer receive hormonal therapy with an
estrogen known as
tamoxifen. Tamoxifen can induce a prolonged response (several years),
and should it cease to be
effective there are then other forms of hormonal therapy which can be
initiated and to which prolonged
responses are also common. Unfortunately this is not the case in
the management of most
men with prostate cancer.
This section of The Prostate Cancer InfoLink will attempt to summarize
the major options which are
currently available to the hormone-refactory prostate cancer patient.
It should be recognized that this,
like therapy of other stages of prostate cancer, is an situation in which
there are multiple avenues of
ongoing basic and clinical research. The options which are listed in this
section should not be
considered to be exclusive. Your physician may well offer you any one of
several other therapeutic
possibilities (either as a part of a clinical trial or otherwise) which
are not mentioned below.
Warning to patients
Regrettably, at this time, no form of hormone-refractory prostate
cancer is curable. All the
available forms of therapy are palliative, which means that they
can be used only to slow the progression
of the disease and to relieve symptoms.
Regardless of the type of hormonal therapy which the patient has previously
received (e.g.,
orchiectomy,
combined hormone therapy,
or others), once a patient begins to fail
hormone therapy his
options are limited. Unfortunately, at the present time, there are no
forms of therapy available which
can offer prolonged responses to the hormone-refractory prostate cancer
patient.
The wise patient will listen carefully to his physician if he wishes to
participate in one or more of the
many clinical trials which open for enrollment regarding the treatment of
hormone-refractory prostate
cancer. A wide range of these trials should be properly categorized as
pilot trials. This means
that the trial is being carried out to see whether there is enough evidence
of clinical response in a small
number of patients to justify a larger and more elaborate trial. Pilot
trials are not usually carried out
with great hopes of prolonged clinical responses in the majority of
patients, and, because they are often
carried out on patients who have exhausted the known effective therapeutic
options, it should be
understood that there are significant risks involved in such clinical
trials.
First considerations
It is generally considered that for the patient who begins to fail
hormonal therapy there are two
immediate possible opportunities, depending upon the form of therapy he
has previously been
receiving:
- For the patient who has received combined
hormonal therapy
with an LHRH agonist and an antiandrogen or with an orchiectomy and an
antiandrogen, there is the
option of antiandrogen withdrawal (stopping the antiandrogen). In many
patients this action will result
in a short-term decrease in PSA level (usually of the order of weeks or
months). This so-called
"antiandrogen withdrawal
effect" is discussed
in more detail elsewhere. The precise nature of the response to
antiandrogen withdrawal appears to be
related to the form of antiandrogen used.
- For the patient who has received an LHRH agonist (with or without an
antiandrogen) to suppress
his testosterone level, this primary suppression of testosterone should be
maintained. This can be
achieved either by maintaining the patient on the LHRH agonist
or by giving the patient
an orchiectomy.
The patient who has already received an orchiectomy will clearly continue
to have a suppressed
testosterone level regardless of other forms of therapy which may be
considered.
Secondary forms of hormonal therapy
Secondary hormonal therapy has traditionally been used in a variety of
attempts to minimize the rising
levels of circulating androgens or to block the effects of those androgens
on prostate cancer cells and
thus limit growth of prostate cancer cells.
The variety of secondary forms of
hormonal manipulation
is considerable and they have been addressed in detail in a separate
section. Currently available classes
of secondary hormonal manipulation include:
- Forms of testicular androgen suppression
- Forms of adrenal androgen suppression
- Additional androgen receptor blockade
- Cellular receptor activation
- The use of estrogens and progestins.
The Prostate Cancer InfoLink wishes patients to be very clear that
secondary forms of hormonal
manipulation are generally of limited benefit. To quote from a recent
major text:
Responses are primarily subjective in nature, and there is no evidence
that any of these therapies
increase patient survival or have consistent palliative effects. ... In
those patients who are ineligible or
unwilling to consider [participating in clinical trials of invetigational
agents], a second hormonal
intervention is not unreasonable. The choice of therapy is dependent upon
numerous factors, including
the performance status of the patients, intercurrent illnesses, and prior
hormonal therapy. Treatment
must be individualized based on these factors, and it must be emphasized
to the patient and family that
this approach is purely palliative.
[From Smith DC, Bahnson RR, Trump DL. Secondary hormonal
manipulation. In Vogelzang NJ, et al., eds, Comprehensive Textbook of
Genitourinary Oncology,
Williams and Wilkins, Baltimore, MD, 1995; 885-890.]
Radiation therapy
Radiation therapy is used extensively in the management of
hormone-refractory prostate cancer in order to help manage pain associated
with the growth of bone metastases. There are two basic forms of radiation
therapy available to assist patients with such problems:
- External beam radiation therapy directed
to alleviate pain at specific sites of growth of bone metastases (e.g., the
spine, the long bones)
- Injectable radiotherapeutic agents
such as strontium-89 (radionuclides) which tend to be absorbed into
growing areas of bone (such as bone metastases) and therefore are able to
give relief by slowing the growth of bone metastases.
It is not uncommon for these two form of radiation to be used in
combination.
Suramin therapy
In the late 1980s it was discovered that a very old pharmaceutical known
as suramin had activity in the treatment of patients with hormone-refractory
prostate cancer. For the past few years a number of clinical research
groups have been attempting to define the precise value of
suramin in the treatment of
hormone-refractory prostate cancer.
There are significant problems related to the widespread use of suramin,
and these problems still have to be resolved. We do not completely
understand how it works. If improperly used it has a range of
severe potential toxicities. It induces adrenal insufficiency and patients
are therefore likely to require permanent glucocorticoid and
mineralocorticoid replacement therapy following suramin therapy.
Chemotherapy
Cytotoxic chemotherapy, one of the commonest forms of therapy for the
majority of cancers, has been relatively unsuccessful in the treatment of
hormone-refractory prostate cancer. Quite why this is the case we still do
not know. However, it probably has something to do with the fact that, by
comparison with other cancers, prostate cancer is a very slowly growing
disease.
A detailed discussion of
cytotoxic chemotherapy in hormone-refractory prostate cancer
is available. The basic content of this section includes:
- Discussion of the use of single chemotherapeutic agents
- The potential role of combination chemohormonal therapies.
Other forms of treatment for hormone-refractory disease can be learned
about in the section on experimental therapies (see below).
Newer experimental approaches
In the past there were a limited range of methods available for attempting
to kill metastatic cancer cells. However, the vast increase in our
knowledge of molecular biology and biochemistry in the past 20 years has
led to a whole series of potential new therapeutic strategies for the
management of hormone-refractory prostate cancer.
It is extremely important for patients to recognize, however, that
the majority of these new therapeutic stategies are in early experimental
stages of their evolution. It is always possible that a piece of
outstanding research will lead to a sudden advance in knowledge and,
consequently, a sudden evolution in the treatment of hormone-refractory
prostate cancer. At the present time, however, The Prostate Cancer
InfoLink strongly advises patients to understand that the types of therapy
which will be discussed in this section are unlikely to offer major
clinical benfits to patients who are already afflicted with
hormone-refractory disease. Regrettably, we still have too much to learn
about the biology of prostate cancer and how it can be transformed.
The section on
emerging and experimental approaches to the treatment of hormone-refractory prostate cancer
includes information on
- Gene therapy
- Immunotherapeutics
- Differentiation therapies
- Induction of apoptosis (programmed cell death)
- Regulation of cell signalling systems
.
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