Injectable Radiopharmaceuticals in
the Management of Hormone-Refractory Prostate Cancer
Last Revised January 21, 1996
[NOTE: Developments in the subject may change this information. For education only.]
Introduction |
General overview |
The types of radiopharmaceuticals |
Clinical use of strontium-89 |
Combination of strontium-89 with local field radiation |
Relative efficacies of strontium-89 and wide-field radiation |
Future possibilities
Introduction
Editorial note: This introduction is very similar to that at the
beginning of the section on use of external beam radiation therapy in the
management of hormone-refractory prostate cancer patients and can be skipped if
you have already read that section. [Note was on original page.]
The value of radiation therapy in the management of metastatic prostate cancer
lesions is undisputed. Basically, three forms of radiation therapy are
available for management of such lesions: local field external beam
radiation, wide-field external beam radiation, and the use of injectable
radiopharmaceuticals. The use of
external beam radiation therapy has been addressed in a separate section.
In the past, about half of all newly diagnosed prostate cancer patients
presented with evidence of metastatic prostate cancer, and in the majority
of those patients, the metastases included bone metastases. However, with
the introduction of the PSA test it appears that only about 30% of
patients diagnosed now have any clinical symptoms suggestive of prostate cancer,
and (at least in the US) metastatic bone disease in newly diagnosed patients
is becoming relatively rare. However, 85% of the men who die of prostate cancer in the US
(which is 3% of the men diagnosed with the disease) have bone metastases.
On the basis of the 1995 estimate of 240,000 newly diagnosed patients, this
implies that at least 6,000 of that 240,000 will go on to die of the disease
with bone metastases.
In other sections we have seen how hormonal therapies of differing types
are commonly used to delay the progression of advanced prostate cancer and
extend survival while improving the quality of life for many patients. (For
links to such sections, please return to
the overview on the treatment of advanced
disease). However,
there are some patients for whom such therapy is insufficient. In many such patients
the use of radiotherapy can give relief from bone pain, at least temporarily, when
properly implemented.
This section will not attempt to address the details of implementation of
injectable radionuclide therapy for the management of metastatic bone
disease in patients refractory
to hormonal therapy. Rather, it will summarize the most critical issues
that patients and family members may need to appreciate when this type of therapy is offered or
recommended.
General overview
The use of radiopharmaceuticals for the treatment of bone pain
related to cancer
has a long history. However, until recently the adverse reactions
associated
with the use of these agents tended to outweigh the clinical benefit.
The approval of
strontium-89 (Metastron/Amersham) by the US Food and Drug Administration
in 1994 has made the first injectable
radiopharmaceutical available in the US for the treatment of prostate and
breast cancer-related bone pain.
This type of therapy is considered appropriate for selected
hormone-resistant prostate cancer patients
with multiple pain-causing metastatic sites. There appears to be a
divergence of opinion between groups of specialists as to whether
this form of therapy should be used before or after other forms of radiation
treatment. Certainly it can be used in combination with local field
radiation.
Radionuclide therapy is not considered to be appropriate as sole
treatment for
- Patients with fractures (or potential fractures)
- Patients with spinal cord or nerve root compression
- Patients who show low levels of radionuclide uptake on bone scan
- Patients with large non-boney metastatic lesions.
In addition, there are some patients who are inappropriate candidates for
radiopharmaceutical therapy for other clinical reasons:
- Patients with inadequate renal (kidney) function
- Patients with insufficient hematologic function (i.e., insufficient
ability to make new blood cells)
- Patients with a life expectancy of less than 6 weeks
- Patients with urinary incontinence.
Finally, because bone-seeking radionuclides compete with calcium for uptake
by newly forming bone cells, patients who are receiving calcium-containing
drugs
for other reasons must stop taking these drugs prior to treatment, or, if
they
cannot stop taking these drugs, are probably unsuitable for radionuclide
therapy.
The types of radiopharmaceuticals
There are basically two types of radiopharmaceutical or radionuclide which
have
been or are being used in the treatment of bone metastases: (1) pure
bone-seeking
radioisotopes such as strontium-89 and phosphorus-32 and (2) radioisotopes
which
have been complexed with other bone-seeking agents (e.g., samarium-153,
rhenium-186, and iodine-131).
Phosphorus-32 was one of the first radionuclides used in the treatment of
bone
metastases. However, it was significantly associated with hematologic
toxicities.
Strontium-89 is by far the most commonly used radionuclide available in the
US. At least in the US, samarium-153 and rhenium-153 are investigational
agents only, and have not been approved for clinical use in the treatment
of bone pain related to
prostate cancer.
Clinical use of strontium-89
The clinical data on the use of strontium-89 in the management of prostate
cancer-related
bone pain is complex and difficult to interpret. Published response rates
vary between 40 and 90% depending upon dosing, patient selection, extent of
disease, and other
criteria. One study has even indicated that there was no pain relief
provided
by this agent at doses of 75 MBq. However, in a contradictory finding, this
same study appeared to indicate that treatment with strontium-89 at this dose level
offered the treated patients a survival benefit over patients who went
untreated! (These data have yet to be substantiated in further studies.)
The most appropriate way to consider the currently available data on the
use of
strontium-89 appears to be as follows:
- Patients with lower levels of disease extent are more likely to gain
pain relief (50-75%) than patients with multiple extensive bone metastases
(40-50%).
- Approximately 10% of patients will become pain free.
- Pain flare can occur and may last for 2-4 days.
- Patients who suffer pain flare usually respond better over time than
those patients who do not suffer pain flare.
- Pain relief commonly occurs 2-3 weeks following treatment.
- Duration of pain relief is usually of the order of 3-6 months.
Treatment with strontium-89 can be repeated after a period of not
less than 3 months, assuming adequate hematologic function. However, it
is generally the case that the degree of pain relief will decline with
each repeat dosing.
Combination of strontium-89 with local field
radiation
It is not unusual for the radio-oncologist to recommend the combination of
local field radiation to one or two specific sites of larger metastases
with the use of radiopharmaceutical treatment. For further information
on the use of local field radiation, please see the section on
external beam radiation therapy in the
treatment of hormone-refractory prostate cancer.
Relative efficacies of strontium-89 and wide-field
radiation
Most radio-oncologists and radiotherapists consider that strontium-89 is less
beneficial than wide-field radiation therapy for the treatment of patients with
multiple metastatic sites. However, the available data are limited and
there has been no specific randomized trial among groups of comparable patients
which would allow us to draw this definitive conclusion. Thus, to what extent
this belief is correct and to what extent it reflects the physician's greater
general familiarity with external beam radiation is open to some question.
What certainly is true is that wide-field radiation and local field radiation
can be used to treat bone and non-bone metastases, whereas injectable
bone-seeking radionuclides affect primarily bone-related metastases.
Future possibilities
It is possible that newer injectable radioisotope-based products will become
available over time which will
offer greater ability to be targeted not only to bone-related metastases
but to prostate cancer-related metastases of any type. Such "magic
bullet"-type, radioisotope-based products may be expected to include
radioisotopes
linked to monoclonal antibodies and to other carefully selected
biochemicals. However, it may be many years before
it is possible to bring these radiopharmaceuticals into widely-available
use. At
present such forms of therapy are experimental.
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