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The Prostate Cancer InfoLink

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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The content in this section of the Phoenix 5 site was originally developed by CoMed Communications (a Vox Medica company) as part of The Prostate Cancer InfoLink. It is reproduced here with the permission of Vox Medica.

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