Approved indication: metastatic
prostate
cancer
Zytiga
(Janssen-Cilag)
250 mg
tablets
Australian Medicines
Handbook section14.3.1
Androgens have an important role in the progression
of prostate cancer. While castration can reduce
progression, the cancer eventually becomes
castration resistant and requires chemotherapy with
drugs such as docetaxel. As androgen activity is
increased at this late stage of the disease,
anti-androgen treatments have been researched.
Abiraterone is an inhibitor of cytochrome P450 (CYP)
C17. This enzyme is involved in androgen synthesis,
so inhibiting it decreases the concentrations of
testosterone and other androgens. When given alone
abiraterone can cause secondary hyperaldosteronism.
To reduce this problem it should be given with
prednisone or prednisolone.
This combination was used in a phase II trial to
treat 58 men with metastatic prostate cancer which
had failed to respond to docetaxel. The response to
therapy was assessed by changes in the men’s
concentrations of prostate specific antigen (PSA).
This declined by at least half in 36% of the men.
The median time to PSA progression was 169
days.1
The same daily dose of abiraterone (1 g orally) was
then used in a placebo-controlled phase III trial in
1195 men who had been previously treated with
docetaxel. These patients also took prednisone 5 mg
twice daily. The median follow-up was 12.8 months.
There was a decrease of 50% or more in the PSA
concentration in 29% of the men who took abiraterone
and in 6% of the placebo group. The time to PSA
progression was 10.2 months with abiraterone and 6.6
months with placebo. In the abiraterone group, 42%
of the patients died compared with 55% of the
placebo group. Overall survival was 14.8 months with
abiraterone and 10.9 months with placebo.2
In the phase III trial the most common adverse events
were fatigue, nausea and back pain, but they
occurred at a similar frequency in the placebo
group. Hypokalaemia, oedema and fluid retention were
more frequent with abiraterone. Less frequent
adverse events which occurred more often with
abiraterone than placebo included urinary tract
infections, hypertension and cardiac disorders, such
as arrhythmias and heart failure. Patients with
clinically significant heart disease or uncontrolled
hypertension were excluded from the trial.2
Abiraterone can increase liver enzymes, so liver
function must be monitored frequently. Treatment may
need to be reduced or stopped depending on liver
function. If prednisolone is stopped abruptly there
is a risk of adrenocortical insufficiency.
Abiraterone is metabolised by CYP3A4, but
interactions with strong inducers and inhibitors of
the enzyme have not been evaluated. CYP1A2 and
CYP2D6 are inhibited by abiraterone so there is a
potential for interactions with drugs which are
metabolised by these enzymes. These include codeine,
oxycodone and tramadol. Only 5% of the dose is
excreted in the urine and there is no recommendation
for a reduced dose in renal disease. Abiraterone
must not be taken with meals because food alters
absorption.
The options for treating metastatic prostate cancer
have increased, but the prognosis is still poor.
Patients may prefer oral abiraterone to intravenous
cabazitaxel, with its cytotoxic adverse effects, but
the drugs’ effectiveness has not yet been compared.
The use of abiraterone in earlier stages of prostate
cancer is being investigated. A trial involving men
with metastatic castration-resistant prostate cancer
was recently unblinded so patients in the placebo
group could be switched to active treatment because
of the emerging benefit of abiraterone.
manufacturer provided the
product information
The Transparency Score (
) is explained in New drugs:
transparency', Vol 37 No 1, Aust Prescr
2014;37:27.
Notes on references
At the time the comment was prepared, information
about this drug was available on the web site of
the Food and Drug Administration in the USA (www.fda.gov).
At the time the comment was
prepared, a scientific discussion about this
drug was available on the website of the
European Medicines Agency (www.emea.europa.eu).