What is Intermittent Hormonal Therapy?
Last Revised December 5, 1995
[developments in hormone therapy since 1995 may change this material]
Introduction |
Benefits and risks |
Current recommendations for intermittent CHT
Introduction
The concept of intermittent hormonal therapy is not new. Whitmore and
some of his colleagues attempted to apply the principle of this type of
therapy using diethylstilbestrol (DES) in the 1970s. However, the drugs
then available were not appropriate to this type of hormonal
manipulation and the patients also may not have been early enough in
their disease.
The basic concept behind intermittent hormonal therapy for advanced
prostate cancer is very simple. Combined hormone therapy is first used
to lower the patient's PSA level. If the PSA level stabilizes at an
appropriately low level, treatment is stopped and the patient's PSA is
carefully monitored. Should the PSA start to rise again, the combined
hormone therapy is reinitiated. In theory this cycle of events can be
repeated multiple times.
Intermittent hormonal therapy has been given a new lease on life by the
availability of the LHRH agonists and the nonsteroidal antiandrogens. In
the early 1990s, Goldenberg and his colleagues in Vancouver, Canada,
carried out the work which gave the momentum for current and extensive
trials to ascertain the real clinical value of this technique.
Benefits and risks
Intermittent hormonal therapy comes with a number of potential benefits
and a number of potential risks. It is important for the patient to
understand these.
Potential benefits
The potential benefits of intermittent hormonal therapy are largely to
do with the patient's quality of life. The following is a general list
of the more important perceived benefits:
- When the patient is off therapy, he will normally
recover sexual function, thus overcoming one of the major perceived
drawbacks of hormonal therapy for advanced prostate cancer, which is
impotence.
- When the patient is off therapy, he will not suffer from the
other common side effects of treatment with LHRH agonists and
antiandrogens (e.g., hot flashes, gynecomastia, loss of muscle tone,
gastroenterological problems, etc.), and will thus have an improved
quality of life.
- Reduction in the overall quantity of hormonal therapy may reduce the
likelihood of the proliferation of androgen-independent prostate cancer
cells and thus the likelihood of development of hormone resistance.
Potential risks
By contrast, the only real risk associated with the use of intermittent
hormonal therapy is that the disease may progress faster because of its
ability to progress while the patient is not actively receiving
treatment.
Assessing the risk/benefit equation
As is often the case in assessing how to treat prostate cancer, doctor
and patient are faced with a decision about their valuation of the
potential benefits as compared to the potential risks. The patient who
values life at all costs, regardless of the quality of that life, is
likely to consider (based on currently available data) that continuous
long-term hormonal therapy is most likely to offer him the longest
possible survival opportunity. On the other hand, the patient who
values life only if it comes with certain levels of quality may be more
likely to consider that intermittent hormonal therapy is a reasonable
option to think about.
Current recommendations for intermittent CHT
[Reminder: This was written in 1995.]
There are, as yet, no absolute recommendations for "correct" methods for
carrying out intermittent hormonal therapy. This form of therapy is
still experimental, and a number of clinical trials are either in
progress or in the development stage. The Prostate Cancer InfoLink
wishes to emphasize that the true value of intermittent hormonal therapy
will only be known when we have data that clearly indicate the survival
opportunity available using this type of therapy and the associated
adverse reactions to the pharmaceuticals used.
Having said that, the following generalized protocol indicates the type
of treatment program which is being tested or is under discussion as a
method of testing the value of intermittent hormonal therapy. It could
be several years before the true value of such a protocol is known.
- Patients with advanced prostate cancer (stage D2 or M1) are
eligible. They must have received no prior long-term hormonal therapy
(and in some trials no prior hormonal therapy at all).
- The patients are randomized to receive either standard CHT
or intermittent CHT. CHT is normally given in the form of
monthly LHRH agonist injections together with oral nonsteroidal
antiandrogen therapy.
- All patients are initially treated for a period of 1-3 months unless
they either show clear signs of disease progression and must be
withdrawn from the trial or they have to withdraw from the trial for
some other reason (e.g., adverse reactions to pharmaceuticals).
- Patients receiving intermittent CHT, and whose PSA level drops to
below 4 ng/ml (i.e., to normal levels), are maintained on CHT for a
total of 6-8 months until the physician is sure that the PSA has
stabilized at this normal level.At this point their therapy is
stopped. (The patients in the so-called "control group" who are
receiving continuous hormonal therapy for purposes of comparison are
maintained on their CHT throughout the trial.)
- Once therapy has been stopped, intermittent CHT patients are
monitored on a regular basis for any indication that their disease has
started to progress again. (The commonest sign of such progression is a
rising PSA.)
- The PSA of patients receiving intermittent hormonal therapy is
normally allowed to rise to a previously determined level (e.g., 20
ng/mL). Once it reaches that level, the entire cycle of combined
hormonal therapy, stabilization of PSA level, cessation of therapy,
etc., can be reinitiated.
The objective here is to determine whether stopping and starting CHT is
as good or better than continuous CHT with respect to the development of
hormone-resistant prostate cancer, the ultimate survival of the patient,
and the quality of life of the patient throughout this period of
time.
There are many centers at which intermittent hormonal therapy is being
tested in a variety of forms. Patients who are interested in the
possibility of participating in clinical trials of this type of therapy
should consult their doctors. Patients who wish to receive this type of
therapy without participating in clinical trials can also ask
their doctors about this. The Prostate Cancer InfoLink has been
informed that some physicians will already provide this type of therapy
to appropriately informed patients, usually with the understanding that
there are few data to support the long-term survival benefits of this
type of therapy at this time.
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