New restrictions have been placed on the use of radium-223 for the treatment of metastatic prostate cancer following a safety review by the European Medicines Agency (EMA). The review concluded that the use of radium-223 is associated with an increased risk of fractures and a possible increased risk of death.
The EMA has imposed the following new restrictions on the use of radium-223:
Restrict use to patients who have received two prior treatments for metastatic prostate cancer, or who cannot receive other treatments
Do not use with abiraterone and prednisolone (this combination is contraindicated)
Do not use with other systemic cancer therapies (except hormone therapy)
Do not use in asymptomatic patients (in line with its current indication)
Do not use in patients with a low number of osteoblastic bone metastases.
The safety review was prompted by findings from a phase III trial (ERA-223) comparing radium-223 in combination with abiraterone and prednisolone against placebo in combination with abiraterone and prednisolone in patients with asymptomatic or mildly symptomatic metastatic castration-resistant prostate cancer. Patients given combination treatment with radium-223 were found to be at risk of dying earlier (2.6 months earlier on average) and at greater risk of fractures (28.6% versus 11.4%) compared with patients given placebo.
The EMA said the higher risk of fractures may be due to the accumulation of radium-223 in areas of the bone that have already been damaged (e.g., by osteoporosis). However, the reasons for the possible earlier death seen in the trial are not fully understood.See Management: approach See Management: treatment algorithm
Second leading cause of cancer mortality in men in the US.
Uncommon in men aged under 50 years.
Prostate-specific antigen and digital rectal examination are key diagnostic tools used in screening.
Management may be expectant or definitive.
In the US, overall 5-year survival rate is around 100% for local- and regional-stage prostate cancer, and around 30% for distant-stage prostate cancer (based on data from 2007 to 2013).
A malignant tumour of glandular origin, situated in the prostate. It is most commonly seen in older men; between 2011 and 2015 the median age at diagnosis in the US was 66 years. 
Richmond Radiation Oncology Associates
Bon Secours Cancer Institute
TJW declares that he is the principal investigator of an R-21 NIH research grant investigating the tumour-mediated immune responses in African-American men with prostate cancer.
Department of Radiation Oncology
University of Texas MD Anderson Cancer Center
MSA declares that he has no competing interests.
Clinical Oncology Registrar
St Luke's Cancer Centre
Royal Surrey Hospital
EA has received consultation fees from the following organisations during the past 3 years: Blue Cross/Blue Shield Association, Sanofi-Aventis, Ferring Pharmaceuticals, Pfizer Corporation, American Urological Association, National Institutes of Health, Accreditation Council for Graduate Medical Education, Royal Hallamshire Hospital, Hartford County Medical Association. EA owns shares in Pfizer Pharmaceuticals, Johnson and Johnson, and General Electric Corporation.
UConn Medical Group
University of Connecticut Health Center
PA declares that he has no competing interests.
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