Dr. Silberstein presents an excellent overview of the use of radiopharmaceuticals in the treatment of osseous metastasis. This article provides general information about the various isotopes used in therapy, and also presents a balanced discussion of the scientific literature involving some of the more controversial aspects associated with the use of radiopharmaceuticals.
Radiopharmaceuticals are used most widely in the treatment of osteoblastic metastases from prostate cancer. This trend is related to the relative frequency of bone metastasis in prostate cancer, the number of men at risk, and the lack of effective therapies for patients who develop hormone-refractory disease. In contrast, there are several systemic treatment options available for patients with breast cancer who develop osteoblastic metastases. Dr. Silberstein mentions that teletherapy (ie, external-beam radiation therapy) is preferred for the treatment of a single focal bone metastasis.
TransCanada Strontium Study
The TransCanada Strontium Study compared the value of adding adjuvant strontium (Sr)-89 (Metastron) to local-field external-beam irradiation for hormone-refractory metastatic prostate cancer involving bone. Although pain associated with one or two target sites responded well to external-beam radiation therapy, the group randomized to Sr-89 demonstrated a significant reduction in the use of analgesics, along with a reduction in the development of new painful sites and a decrease in the use of additional radiotherapy.
This study used a strontium dose of 10.8 mCi. In the United States, a dose of 4 mCi is used approximately three times more often than the 10.8-mCi dose. However, the study reported no statistical difference in survival, despite the use of the higher dose.
A survey of current practices of care for the radiotherapeutic management of osseous metastases has shown increased use of local radiation therapy combined with a radiopharmaceutical. Apart from the use of the generally lower dose of Sr-89 (4 mCi), this practice essentially correlates with one arm of the TransCanada Strontium Study.
Most Widely Used Agents
Dr. Silberstein provides a comprehensive review of the various radiopharmacueticals currently in use. At present, the more widely used isotopes include Sr-89, phosphorous (P)-32, and samarium (Sm)-153 lexidronam (Quadramet). The other radiopharmaceuticals mentionedrhenium (Re)-186 and tin (Sn)-117mare rarely used in clinical practice. Compared to Sr-89, Sm-153 may have the advantage of more rapid hematologic recovery.
An article by Ben-Josef points out that Sr-89 is the radionuclide most widely used by radiation oncologists. Indeed, a survey of 817 practicing physicians indicated that Sr-89 was selected 99% of the time. Nevertheless, Nair compared the use of oral P-32 phosphate with intravenous Sr-89 for the treatment of a variety of osseous metastases and demonstrated equal efficacy between the two radionuclides. There was no significant increase in hematologic toxicity associated with the use of oral P-32, and although the number of patients enrolled in this study was small, the validity of using the more expensive Sr-89 over oral P-32 was appropriately challenged in the article. A confirmatory project involving a larger number of patients would be of value.
Guidelines for the Use of Radiopharmaceuticals
Dr. Silberstein points out important guidelines for the use of radiopharmaceuticals. Patients with bone metastases that are not visible on bone scan are not appropriate candidates for radiopharmaceuticals. Lytic bone metastases (as opposed to blastic bone metastases) would generally fit into this category.
The need to rule out an existing or impending pathologic fracture is also addressed by Dr. Silberstein. The 50% cortical destruction rule is generally effective for identifying patients at risk for pathologic fracture. Extremity metastases also need to be evaluated for risk of pathologic fracture. The baseline leukocyte count of 5 ´ 109/µL and platelet count of 100 ´ 109/µL are practical guidelines. Timing of the administration of radiopharmaceuticals with respect to chemotherapy and teletherapy is also important.
Dr. Silberstein discusses the need to exclude the presence of disseminated intravascular coagulation prior to administering radiopharmaceuticals. Patients with impending cord compression are not candidates for radionuclides. This clinical presentation should be suspected in patients who provide a history of back pain that is aggravated while lying in a recumbent position and improved while upright. Patients presenting with this history or with neurologic findings should be evaluated for spinal cord compression. Dr. Silberstein also comments on the inadequacy of radiopharmaceuticals for the treatment of bone involvement caused by direct extension from soft-tissue tumors.
Limited Osseous Metastases
There has been interest in using radiopharmaceuticals to treat patients who present with more limited osseous metastases. The hypothesis is that an improvement in survival may be achieved by treating osseous metastases when the overall tumor burden is lower. This approach may merit study, particularly in the absence of other effective systemic therapies. Patients in this category could have relatively long survival times. A recent article documented two case reports of acute myelogenous leukemia developing in men treated with Sr-89. Although most patients with osseous metastasis do not live long enough to be at risk for this disease, this potential iatrogenic complication should be considered when prescribing radiopharmaceuticals.
The article by Dr. Silberstein provides an excellent review of the use of radiopharmaceuticals for the treatment of painful osteoblastic metastases and ends appropriately with questions that remain unanswered. Nonetheless, there appears to be an evolving standard of practice regarding the indications for radionuclides and the art of their administration. This form of therapy represents another tool that can be used to assist the oncology patient in greatest need.