Bone-seeking
radionuclides including
samarium-153 ethylene diamine tetramethylene
phosphonate and
strontium-89 have been used for decades in the palliation of
pain from bone
metastases especially from
prostate cancer. Emerging evidence of improved survival in metastatic
castration-resistant
prostate cancer (CRPC) with the first-in-class α-
radionuclide,
radium-223 (Ra) has rekindled interest in the role of bone-seeking
radionuclide therapy.We review the literature for randomized controlled trials of bone-seeking
radionuclides and explore some of the issues regarding the optimal use of these agents. In particular, we discuss dose, dose rate, radiobiology, and quality of radiation and postulate on potential future directions in particular combination schedules. β-Emitting, bone-seeking
radionuclides have proven ability to control
pain in
prostate cancer metastatic to bone with
pain response rates in the order of 60% to 70% when used as single agents. Most of the published trials were underpowered to detect differences in survival; however, there is evidence of the potential for disease modification when these agents are used in combination with
chemotherapy or in multiple cycles.Data from the recent phase III ALSYMPCA trial that compared Ra to placebo in symptomatic CRPC demonstrate a significant improvement in median overall survival of 3.6 months for patients with symptomatic CRPC metastatic to bone treated with 6 cycles of the α-emitting
radionuclide Ra compared with placebo. The success of Ra in improving survival in CRPC will lead this agent to become part of the treatment paradigm for this disease, and with such an excellent safety profile, Ra has huge potential in combination strategies as well as for use earlier in the natural history of metastatic
prostate cancer.