Abstract
Background
Abiraterone acetate (AA) inhibits androgen biosynthesis and prolongs survival in men
with metastatic castration-resistant prostate cancer (mCRPC) when combined with prednisone
(P). Resistance to therapy remains incompletely understood. In this open-label, single-arm,
multicenter phase II study we investigated the clinical benefit of increasing the
dose of AA at the time of resistance to standard-dose therapy.
Patients and Methods
Eligible patients had progressive mCRPC and started AA 1000 mg daily and P 5 mg twice
daily. Patients who achieved any prostate-specific antigen (PSA) decline after 12
weeks of therapy continued AA with P until PSA or radiographic progression. At progression,
AA was increased to 1000 mg twice daily with unchanged P dosing. Patients were monitored
for response to therapy for a minimum of 12 weeks or until PSA or radiographic progression.
The primary end point was PSA decline of at least 30% after 12 weeks of therapy at
the increased dose of AA.
Results
Forty-one patients were enrolled from March 2013 through March 2014. Thirteen men
experienced disease progression during standard-dose therapy and were subsequently
treated with AA 1000 mg twice per day. Therapy was well tolerated. No PSA declines ≥
30% nor radiographic responses were observed after 12 weeks of dose-escalated therapy.
Higher baseline dehydroepiandrosterone levels, lower circulating tumor cell burden,
and higher pharmacokinetic levels of abiraterone and abiraterone metabolites were
associated with response to standard-dose therapy.
Conclusion
Increasing the dose of abiraterone at the time of resistance has limited clinical
utility and cannot be recommended. Lower baseline circulating androgen levels and
interpatient pharmacokinetic variance appear to be associated with primary resistance
to AA with P.
Keywords
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Article info
Publication history
Published online: June 02, 2017
Accepted:
May 25,
2017
Received in revised form:
May 22,
2017
Received:
April 4,
2017
Footnotes
This trial is registered at Clinicaltrials.gov: NCT01637402.
Identification
Copyright
© 2017 Elsevier Inc. All rights reserved.
