©TheCanadian Journal ofUrology™: International Supplement, April 2014
did experience a “flare” phenomenon. There was a
significant decline in alkaline phosphatase amongst
theprostatepatient cohort. Nodose limiting toxicities
(defined as platelets < 20 x 10
9
/L, or neutrophils < 0.5
x 10
9
/L) were experienced. Myelosuppression was
mild and reversiblewith anadir 2-4weeks after drug
administration. However, nonhematologic toxicity
consisting of transient diarrhea (40% of patients),
fatigue (25%ofpatients), andnauseaorvomiting (20%
ofpatients) occurred.
The phase II double blind placebo control trial
randomized 64 men with CRPC to receive four
intravenous injections of either 50kBq/kg of radium
223orplaceboevery4weeks. Theprimaryendpoints
were change in bone-alkaline phosphatase and time
to skeletal related events (SREs).
29,45
At 4 weeks
alkalinephosphatases levelswere -65% in the radium
223 arm and +9.3% in the placebo arm (p < 0.0001).
Time to skeletal related events was not statistically
significant (14weeksversus11weeks,p=0.26). There
was a statistically significant change in time to PSA
progression of 26weeks versus 8weeks andmedian
change in relative PSA (-24% versus +45%). There
was a trend to improvement in overall survival (65.3
weeks versus 46.4 weeks, p = 0.066), suggesting a
potential survival advantage. Hematological toxicity
wascomparable in the twoarmsandnotedonly in the
first 4weeks of treatmentwith radium 223.
TABLE 2.
Administration and strategies tomanage side effectsof therapy for radium 223
Indication
• Radium223 is indicated for the treatmentofpatientswithcastrationresistantprostate
cancer, symptomatic bonemetastases andnoknownvisceralmetastaticdisease
Administration
• Radium 223 is administeredby slow intravenous injectionover 1minute
• Prior toadministration, the intravenousaccess lineorcannulashouldbeflushedwith
isotonic saline
Strategies tomanage side effects
Hematologic
• Hematologicevaluationsshouldbeperformedatbaselineandprior toevery injection
of radium 223
• Before thefirst administration
absoluteneutrophil count (ANC) shouldbe ≥ 1.5x 10
9
/L
platelet count shouldbe ≥ 100x 10
9
/L
hemoglobin ≥ 10g/dL
• Before subsequent administration
ANC shouldbe ≥ 1x 10
9
/L
platelet count shouldbe ≥ 50x 10
9
/L
• Ifcountsdonotrecover to theabovevalueswithin6-8weeksofadministration,despite
supportive care, treatment shouldbediscontinued
• Supportive care includes transfusions andgrowth factors
• Radium223shouldbediscontinuedintheeventoflifethreateningcomplicationsdespite
supportive care for bonemarrow failure
• Patients are instructed to report signs of bleedingor infection
Non-hematologic
• Patients are instructed to remainwell hydrated and tomonitor oral intake
• Patientsare instructed toreportsignsofdehydration,hypovolemia,urinaryretention
or renal failure/insufficiency
• Patientsare instructed to followgoodhygienepracticesforat least1weekpost injection
including:
flushing the toilet several times after use
promptlywashing soiled clothing separately
• Caregivers are instructed touseuniversal precautions including:
handwashing
usinggloves andbarrier gownswhenhandlingbodilyfluids
patientsare instructed tousecondomswhensexuallyactiveand femalepartners
are instructed tousebirthcontrolup to6months from last radium223 injection
73
DenETAL.
