©TheCanadian Journal ofUrology™: International Supplement, April 2014
60
Practical guide to theuseof abiraterone in castration resistant prostate cancer
TABLE 1.
Adverse events (%) reportedduring treatmentwith abiraterone
All grades
COU-001
COU-002
(post-chemotherapy) (pre-chemotherapy)
abiraterone
placeboarms
abiraterone placeboarms
Hematologic
Anemia
25
28
23
26
General sideeffects
Fatigue
47
44
39
34
Backpain
33
36
32
32
Arthralgia
30
24
28
24
Bonepain
27
30
20
19
Nausea
33
33
22
22
Vomiting
24
26
Constipation
28
32
23
19
Diarrhea
20
15
22
18
Hotflash
10
9
22
18
Urinary tract infection
13
7
12
7
Mineralocorticoideffects
Fluid retention
33
24
28
24
Hypertension
11
8
22
13
Hypokalemia
18
9
17
13
Hepatotoxicity (ALT/AST)
11
9
12
5
Cardiotoxicity
All
16
12
19
16
Atrial fibrillation
2
1
4
5
monitored for hypertension, hypokalemia and fluid
retentionatleastonceamonth. Spironolactoneisavoided
in patients who develop mineralocorticoid-related
side effects due to its mixedAR agonist/antagonist
activity. Instead, eplerenone, a second-generation
mineralocorticoid receptor antagonist (MRA) in doses
of50mg/day-200mg/day(individeddosestwicedaily)
canbeused in combinationwith a salt-restricteddiet.
18
Alternatively, potassium-sparing epithelial sodium
channel antagonists such as amiloride and triamterene
(incombinationwithhydrochlorthiazideifhypertension
is significant) can be used in place of or added to
eplerenone ifnecessary.
16,18
In rare instances, additional
anti-hypertensive agentsmay be necessary in patients
already receivingprednisone, eplerenoneanddiuretics.
Heptatotoxicity
Grade 3 or 4 hepatic transaminase abnormalities (5x
upper limitofnormal-ULN)occurred inapproximately
4% of patients in the phase III studies, usuallywithin
the first 3 months of starting treatment, and more
commonly inmenwhose baselineALT or ASTwere
elevated. Serum transaminasesshouldbemeasuredat
baseline. Transaminases inpatientswithnormal levels
shouldbecheckedevery2weeks for thefirst3months
of therapy, and thenmonthly. Nodose adjustment is
necessary formildhepatic impairment. Formoderate
hepatic impairment (Child-PughClass B) abiraterone
should be started at 250mg daily, and transaminases
shouldbecheckedweeklyforthefirstmonth,thenevery
2weeks for the following2months, and thenmonthly.
If AST or ALT rise above 5 times the ULN, or
bilirubin rises above 3 times the ULN, abiraterone
shouldbeheld. Itshouldbediscontinued if thepatient
hadmoderate hepatic impairment at baseline, but in
patients with normal hepatic function at baseline it
can be restarted at 750mg dailywhen LFT’s decline
to less than 2.5 times the ULN and total bilirubin is
less than 1.5 times ULN. If hepatotoxicity recurs, a
further dose reduction to 500 mg can be attempted
(once levels have fallen below the thresholds given
above), but recurrenceofhepatotoxicityat the500mg
dose requiresdiscontinuationof thedrug.
Cardiotoxicity
Theoverall incidenceof adversecardiaceffectswasnot
statistically increased by abiraterone inCOU-001 (13%
versus11%inplacebo),althoughthefrequencyofcardiac
