Abiraterone acetate, a novel adrenal inhibitor in metastatic castration-resistant prostate cancer.
The androgen receptor remains the key player in patients with castration-resistant prostate cancer (CRPC). Available agents capable of blocking early adrenal androgen production have limited activity and can lead to significant toxicities. Abiraterone acetate, a pregnenolone analog, is a small molecule that irreversibly inhibits CYP17, a rate-limiting enzyme in androgen biosynthesis. Several clinical trials have demonstrated the safety and efficacy of this compound in men with metastatic CRPC. Recently, a randomized phase 3 trial evaluating abiraterone acetate in docetaxel-refractory CRPC patients demonstrated a survival improvement over placebo-treated patients (14.8 vs 10.9 months; HR 0.646; P < 0.0001). A similar trial in the pre-chemotherapy setting has completed accrual and is undergoing analysis. Here we review the rationale and clinical development of abiraterone acetate in men with CRPC.
Department of Solid Tumor Oncology, Cleveland Clinic Taussig Cancer Institute, 9500 Euclid Avenue/R35, Cleveland, OH 44195, USA.
Mohamed
M
Salem
Jorge A
JA
Garcia
D000311:Adrenal Glands / Q000187:drug effects* / Q000378:metabolism; D000726:Androgen Antagonists / Q000627:therapeutic use; D000728:Androgens / Q000096:biosynthesis; D000736:Androstenes; D000737:Androstenols / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use; D017326:Clinical Trials, Phase III as Topic; D006801:Humans; D008297:Male; D009919:Orchiectomy; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000601:surgery; D016032:Randomized Controlled Trials as Topic; D013254:Steroid 17-alpha-Hydroxylase / Q000037:antagonists & inhibitors
D000726:Androgen Antagonists; D000728:Androgens; D000736:Androstenes; D000737:Androstenols; D000970:Antineoplastic Agents; D013254:Steroid 17-alpha-Hydroxylase; C089740:abiraterone
Hematol Oncol Clin North Am. 2006 Aug;20(4):925-34
16861123
J Steroid Biochem Mol Biol. 2002 Jul;81(3):191-201
12163131
Semin Reprod Med. 2004 Nov;22(4):299-309
15635498
Endocr Relat Cancer. 2004 Sep;11(3):459-76
15369448
Cancer Res. 2001 Apr 1;61(7):2892-8
11306464
Arch Androl. 2001 Mar-Apr;46(2):117-25
11297065
J Natl Cancer Inst. 2001 Nov 21;93(22):1687-97
11717329
N Engl J Med. 2004 Oct 7;351(15):1513-20
15470214
Cancer. 1997 Nov 1;80(9):1755-9
9351544
J Clin Oncol. 2008 Oct 1;26(28):4563-71
18645193
Urology. 1973 Aug;2(2):99-102
4358703
J Urol. 2005 Mar;173(3):790-6
15711271
J Endocrinol. 1974 Jan;60(1):117-25
4130214
Lancet. 2010 Apr 24;375(9724):1437-46
20398925
Nucl Recept Signal. 2008 Feb 01;6:e001
18301781
J Urol. 1998 Oct;160(4):1220-9
9751323
Int J Cancer. 2007 Feb 15;120(4):719-33
17163421
J Natl Cancer Inst. 1994 Feb 2;86(3):222-7
7506794
Cancer Res. 2009 Jun 15;69(12):4937-40
19509232
Urol Oncol. 2009 May-Jun;27(3):251-7
19414113
Urology. 2002 Sep;60(3 Suppl 1):132-8; discussion 138-9
12231070
Clin Cancer Res. 2004 Jan 15;10(2):440-8
14760063
J Urol. 2002 Aug;168(2):542-5
12131305
J Clin Oncol. 2009 Aug 10;27(23):3742-8
19470933
J Cell Biochem. 2004 Feb 15;91(3):483-90
14755679
Semin Reprod Med. 2004 Nov;22(4):281-8
15635496
N Engl J Med. 2004 Oct 7;351(15):1502-12
15470213
J Clin Oncol. 2010 Mar 20;28(9):1489-95
20159823
J Clin Oncol. 2005 Nov 10;23(32):8253-61
16278481
Clin Cancer Res. 2007 Apr 1;13(7):2030-7
17404083
J Urol. 1997 Apr;157(4):1204-7
9120902
Br J Cancer. 2004 Jun 14;90(12):2317-25
15150570
Curr Opin Pharmacol. 2008 Aug;8(4):440-8
18674639
Nat Rev Cancer. 2001 Oct;1(1):34-45
11900250
Steroids. 1997 Jan;62(1):133-42
9029728