Pharmacokinetics, pharmacodynamics and clinical efficacy of abiraterone acetate for treating metastatic castration-resistant prostate cancer.
BACKGROUND
Androgen signaling axis (ASA) continues to play a crucial role in castration-resistant prostate cancer (CRPC). One of the proposed mechanisms is the activation of ASA by adrenal and intratumoral androgens. Targeted therapy to deplete such androgen sources should be effective in treating men with CRPC.


METHODS
Abiraterone acetate (AA) is a selective irreversible inhibitor of CYP 17. It is orally administered and is converted to its active metabolite abiraterone by the liver. Increased adrenocorticotrophic hormone drive, however, results in increased risks of hypertension and hypokalemia. In Phase III trials, AA with prednisone was shown to improve survivals in men with metastatic CRPC (mCRPC). The overall tolerability and safety profiles were acceptable.


CONCLUSIONS
It is now accepted that CRPC is not independent of androgen signaling, and targeted therapies to suppress ASA have recently been developed. With multiple high-level evidences of efficacy and safety, AA is considered a breakthrough in the treatment of mCRPC. Current clinical challenge, however, is to better delineate the mechanisms of the disease progression for developments of resistance to targeted therapies. Identification of the drug-resistance patterns would allow better patient selection for each treatment modality.
The State University of New Jersey, Section of Urologic Oncology and Dean and Betty Gallo Prostate Cancer Center, Rutgers Cancer Institute of New Jersey and Rutgers Robert Wood Johnson Medical School , 195 Little Albany Street, New Brunswick, NJ 08903 , USA +1 732 235 2043 ; +1 732 235 6596 ; kimiy@cinj.rutgers.edu.
Christopher Sejong
CS
Han
Rutveej
R
Patel
Isaac Yi
IY
Kim
D000069501:Abiraterone Acetate / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D000728:Androgens / Q000378:metabolism; D000970:Antineoplastic Agents / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm; D006801:Humans; D008297:Male; D058990:Molecular Targeted Therapy; D009362:Neoplasm Metastasis; D018579:Patient Selection; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy* / Q000473:pathology; D015996:Survival Rate
D000728:Androgens; D000970:Antineoplastic Agents; D000069501:Abiraterone Acetate
abiraterone acetate; castration-resistant prostate cancer; clinical efficacy; pharmacodynamics; pharmacokinetics.