Radionuclides for Patients With Painful Skeletal Metastases
Radionuclides for Patients With Painful Skeletal Metastases
Background: Pain from skeletal metastases represents a major burden of advanced disease from solid tumors. Analgesic medications, bisphosphonates, hormonal agents, cytotoxic chemotherapy, and external beam radiotherapy are all effective treatments. However, patients often suffer from diffuse painful metastases and respond poorly to these standard therapies. Bone-seeking radionuclides can specifically target osteoblastic lesions to offer palliation of pain.
Methods: This article offers a narrative review of bone-seeking radionuclides, examines the evidence of safety and efficacy for the treatment of painful skeletal metastases, and presents guidelines for their appropriate use in this patient population.
Results: Seven bone-seeking radionuclides have shown evidence of both safety and efficacy in reducing pain from diffuse skeletal metastases. Sm-EDTMP and Sr are most commonly used in the United States and have been safely utilized for both repeat dosing as well as concurrent dosing with cytotoxic chemotherapy.
Conclusions: Targeted bone-seeking radionuclides are underutilized in the treatment of painful diffuse osteoblastic metastases. Several new agents are in active clinical investigation, and the pending approval of the first alpha-emitting radionuclide (Ra) may offer a new class of agents that provide greater efficacy and less toxicity than those currently available for routine clinical use.
Bone pain arising from symptomatic skeletal lesions is a common cause of morbidity in patients with metastatic cancer, and a majority of patients with diffuse disease require multiple treatment modalities for pain. The most common primary sites of solid tumors giving rise to such lesions are the breasts, prostate, lungs, and kidneys, together representing nearly 80% of all bony metastases. If undiagnosed or inadequately treated, skeletal metastases often lead to profound pain, compression of the spinal cord, hypercalcemia, and pathological fracture of involved bones. Multiple reports suggest a direct correlation between the burden of bony metastases and survival.
Most bone metastases are localized to the red marrow, thus the proclivity for the axial skeleton. Bone metastases are generally classified as osteoblastic (increased formation of bony matrix), osteolytic (increased destruction), or mixed. Although some malignancies give rise principally to blastic or lytic lesions (prostate cancer and multiple myeloma, respectively), most malignancies exhibit a mixed blastic-lytic phenotype. Recently, the interactions between tumor-expressed surface proteins and the bone microenvironment have been better elucidated. Prostate cancer cells often express transforming growth factor beta (TGF-β), which aids in the adhesion to bone matrix and can affect the maturation of osteoclasts. Epidermal growth factor (EGF) may also enhance metastasis by facilitating the migration of cancer cells from circulation and into bone.
Abstract and Introduction
Abstract
Background: Pain from skeletal metastases represents a major burden of advanced disease from solid tumors. Analgesic medications, bisphosphonates, hormonal agents, cytotoxic chemotherapy, and external beam radiotherapy are all effective treatments. However, patients often suffer from diffuse painful metastases and respond poorly to these standard therapies. Bone-seeking radionuclides can specifically target osteoblastic lesions to offer palliation of pain.
Methods: This article offers a narrative review of bone-seeking radionuclides, examines the evidence of safety and efficacy for the treatment of painful skeletal metastases, and presents guidelines for their appropriate use in this patient population.
Results: Seven bone-seeking radionuclides have shown evidence of both safety and efficacy in reducing pain from diffuse skeletal metastases. Sm-EDTMP and Sr are most commonly used in the United States and have been safely utilized for both repeat dosing as well as concurrent dosing with cytotoxic chemotherapy.
Conclusions: Targeted bone-seeking radionuclides are underutilized in the treatment of painful diffuse osteoblastic metastases. Several new agents are in active clinical investigation, and the pending approval of the first alpha-emitting radionuclide (Ra) may offer a new class of agents that provide greater efficacy and less toxicity than those currently available for routine clinical use.
Introduction
Bone pain arising from symptomatic skeletal lesions is a common cause of morbidity in patients with metastatic cancer, and a majority of patients with diffuse disease require multiple treatment modalities for pain. The most common primary sites of solid tumors giving rise to such lesions are the breasts, prostate, lungs, and kidneys, together representing nearly 80% of all bony metastases. If undiagnosed or inadequately treated, skeletal metastases often lead to profound pain, compression of the spinal cord, hypercalcemia, and pathological fracture of involved bones. Multiple reports suggest a direct correlation between the burden of bony metastases and survival.
Most bone metastases are localized to the red marrow, thus the proclivity for the axial skeleton. Bone metastases are generally classified as osteoblastic (increased formation of bony matrix), osteolytic (increased destruction), or mixed. Although some malignancies give rise principally to blastic or lytic lesions (prostate cancer and multiple myeloma, respectively), most malignancies exhibit a mixed blastic-lytic phenotype. Recently, the interactions between tumor-expressed surface proteins and the bone microenvironment have been better elucidated. Prostate cancer cells often express transforming growth factor beta (TGF-β), which aids in the adhesion to bone matrix and can affect the maturation of osteoclasts. Epidermal growth factor (EGF) may also enhance metastasis by facilitating the migration of cancer cells from circulation and into bone.