Format

Send to

Choose Destination
Clin Genitourin Cancer. 2017 Dec;15(6):733-741.e1. doi: 10.1016/j.clgc.2017.05.026. Epub 2017 Jun 3.

High-Dose Abiraterone Acetate in Men With Castration Resistant Prostate Cancer.

Author information

1
Division of Genitourinary Medical Oncology, University of California, San Francisco, CA. Electronic address: terence.friedlander@ucsf.edu.
2
Knight Cancer Institute, Oregon Health and Science University, Portland, OR.
3
Department of Medicine, University of California, San Francisco, CA.
4
Division of Genitourinary Medical Oncology, University of California, San Francisco, CA.
5
Biostatistics Core, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA.
6
Department of Urology, University of California, San Francisco, CA.
7
Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, CA.
8
Department of Urology, Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH.
9
Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH.
10
Epic Biosciences, La Jolla, CA.
11
Division of Genitourinary Medical Oncology, University of California, San Francisco, CA; Department of Urology, University of California, San Francisco, CA.

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.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT01637402.

KEYWORDS:

Acquired resistance; Androgen receptor; Androgens; Hormonal therapy; Primary resistance

PMID:
28655452
DOI:
10.1016/j.clgc.2017.05.026
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center