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radium-223 with antiandrogen therapies such as enzalutamide
or abiraterone is well tolerated (16).
CLINICAL TRIALS
The ﬁrst-in-human trial was conducted in 2000 by Nilsson
et al to study the safety and tolerability of radium-223. They
concluded that radium-223 was tolerated well at therapeutic
dosages, with pain relief and positive eﬀects on serum markers
as indications of its anticancer eﬀect (17).
The BC1-02 was the second clinical study conducted in
2002. It was a randomized double-blind placebo-controlled
multicenter phase 2 trial. This study showed that adverse events,
including serious adverse events, were more common when
patients were not treated with radium-223 (18). Two additional randomized, double-blinded phase 2 trials were conducted (BC1-03 and BC1-04) before starting the ALSYMPCA
(ALpharadin in SYMPtomatic Prostate Cancer) trial (19). The
ALSYMPCA trial, which concluded in 2013, was a randomized, double-blind, multinational phase 3 trial. Testing a total
of six injections of radium-223 per patient, the trial showed a
signiﬁcant improvement in overall survival rates and improved
quality of life with treatment (20). The trial also showed delayed
development of skeletal complications and a signiﬁcant reduction of the risks of spinal cord compression and requirement
for external beam radiation therapy (4). There were no clinically signiﬁcant diﬀerences in hematologic adverse events with
radium-223 treatment (4).
INDICATIONS
Radium-223 is indicated for use in the management of adult
men with CRPC with symptomatic metastases to the bone and
no other visceral metastases. It is given intravenously over 1
minute at 50 kBq/kg body weight every 4 weeks for a total of
6 injections. There is no need for dose adjustment in the elderly
and those with renal or hepatic impairment (1). The main adverse event to look for after administration is bone marrow suppression. This requires a baseline hematological investigation,
with follow-up studies before and after each dose (1). Interval
investigation of hematologic abnormalities is typically done 1
week before each injection. The gap between each injection can
be extended up to 8 weeks if laboratory values are abnormal, to
allow for repeat evaluation. If at 8 weeks the patient continues
to experience a hematologic abnormality, treatment is halted.
DISCUSSION
Current treatment guidelines for mCRPC include hormonal
agents like abiraterone acetate and enzalutamide, the chemotherapeutic agent cabazitaxel, the immunotherapeutic agent
sipuleucel-T, and radium-223 (19, 21).
Radium-223 has been studied in comparison with other
treatment modalities (19). Other bone-targeted therapies, apart
from radiopharmaceuticals, include osteoclast inhibitors like
the bisphosphonate zoledronic acid and the RANKL inhibitor
denosumab. However, neither showed improvement in disease
progression or overall survival (2). According to Hoskin et al,
radium-223 is well tolerated and eﬀective in patients with sympOctober 2017

tomatic mCRPC, irrespective of previous docetaxel use (22).
Also, chemotherapy following treatment with radium-223 is
feasible and appears well tolerated, irrespective of prior docetaxel
use (23). According to Finkelstein et al, the hematologic safety
proﬁle of radium-223 with concomitant EBRT was similar to
that without concomitant EBRT. Therefore, EBRT can be used
additionally with radium-223 for pain palliation (24).There
were no statistical diﬀerences when the treatment was combined with bisphosphonates (4). Trials studying the feasibility
and eﬃcacy of combining radium-223 with other endocrine
modalities are currently ongoing (19).
CONCLUSION
Radium-223 is a ﬁrst-of-its-kind FDA-approved bonetargeting therapeutic agent that positively impacts overall survival, delay in symptomatic skeletal events, and quality of life.
Various clinical trials and their post hoc analyses have proved
its safety and eﬃcacy in treating mCRPC with bone metastases. However, its role in managing micro bone metastases in
early mCRPC is still ambiguous. Ongoing research and trials
are attempting to address various combination therapies and
treatment sequencing strategies. They are also exploring use of
radium-223 for treatment of other cancers like breast cancer,
renal cancer metastases to bone, and thyroid cancer (1, 19) with
osseous metastasis.
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