title: Current paradigms and evolving concepts in metastatic castration-resistant prostate cancer.
abstract: Until recently, docetaxel-based therapy represented the only therapy shown to prolong survival in patients with metastatic castration-resistant prostate cancer (mCRPC). The past year and a half has been marked by unprecedented progress in treatments for this disease. Three positive phase III clinical trials have emerged, each evaluating agents (sipuleucel-T, cabazitaxel and abiraterone) with distinct mechanisms of action. Herein, the three pivotal trials are described alongside both past and current large phase III studies conducted in this mCRPC. The overall survival for patients with mCRPC treated in current clinical trials is considerably longer than noted in the past. We note that more recent trials with older agents have also shown improved survival and discuss potential non-therapeutic biases that influence this critical measure of outcome. The necessity for utilizing randomized trials when evaluating new therapeutics is emphasized given the changing prognosis in this mCRPC.
authors: Division of Genitourinary Malignancies, Department of Medical Oncology and Experimental Therapeutics, City of Hope Comprehensive Cancer Center, Los Angeles, CA, USA.
authors: Sumanta Kumar
authors: SK
authors: Pal
authors: Oliver
authors: O
authors: Sartor
references: N Engl J Med. 2009 Mar 26;360(13):1320-8
references: 19297566
references: J Clin Oncol. 2011 Jun 1;29(16):2191-8
references: 21483004
references: J Clin Oncol. 2010 Mar 1;28(7):1099-105
references: 20100959
references: Cancer Chemother Pharmacol. 2010 Mar;65(4):811-5
references: 20052472
references: J Clin Oncol. 2006 Jun 20;24(18):2828-35
references: 16782921
references: JAMA. 1995 Feb 15;273(7):548-52
references: 7530782
references: Steroids. 1997 Jan;62(1):133-42
references: 9029728
references: J Clin Oncol. 2008 Jan 10;26(2):242-5
references: 18182665
references: J Clin Oncol. 2003 Feb 1;21(3):490-5
references: 12560440
references: Front Biosci. 2007 Sep 01;12:4957-71
references: 17569623
references: N Engl J Med. 2009 Mar 26;360(13):1310-9
references: 19297565
references: Cancer. 2009 Aug 15;115(16):3670-9
references: 19536890
references: J Clin Oncol. 2006 Jul 1;24(19):3089-94
references: 16809734
references: BJU Int. 2005 Dec;96(9):1241-6
references: 16287438
references: Curr Urol Rep. 2009 Jan;10(1):4-5
references: 19116088
references: Lancet. 2010 Apr 24;375(9724):1437-46
references: 20398925
references: J Clin Oncol. 2009 Nov 10;27(32):5431-8
references: 19805692
references: J Clin Oncol. 1999 Jun;17(6):1654-63
references: 10561201
references: J Clin Oncol. 1999 Aug;17(8):2506-13
references: 10561316
references: Clin Cancer Res. 2008 May 1;14(9):2763-7
references: 18451243
references: Cancer. 2007 Nov 1;110(9):1959-66
references: 17886253
references: Clin Prostate Cancer. 2004 Sep;3(2):104-11
references: 15479494
references: J Clin Oncol. 2010 Sep 20;28(27):4247-54
references: 20733135
references: J Clin Oncol. 2010 Mar 20;28(9):1496-501
references: 20159814
references: N Engl J Med. 2004 Oct 7;351(15):1513-20
references: 15470214
references: J Steroid Biochem Mol Biol. 2011 May;125(1-2):23-31
references: 21092758
references: J Clin Oncol. 2003 Apr 1;21(7):1232-7
references: 12663709
references: J Clin Oncol. 2009 Aug 10;27(23):3742-8
references: 19470933
references: N Engl J Med. 2010 Aug 19;363(8):733-42
references: 20818875
references: Clin Interv Aging. 2010 Dec 03;5:395-402
references: 21152241
references: Lancet. 2010 Oct 2;376(9747):1147-54
references: 20888992
references: BJU Int. 2008 Mar;101 Suppl 2:11-5
references: 18307687
references: N Engl J Med. 2009 Jun 11;360(24):2516-27
references: 19516032
references: Clin Cancer Res. 2009 Dec 1;15(23):7412-20
references: 19934295
references: J Clin Oncol. 1986 Mar;4(3):414-24
references: 2936872
references: J Clin Oncol. 2012 May 1;30(13):1534-40
references: 22454414
references: CA Cancer J Clin. 2010 Sep-Oct;60(5):277-300
references: 20610543
references: Expert Rev Vaccines. 2005 Jun;4(3):259-74
references: 16026242
references: N Engl J Med. 1997 Jul 31;337(5):295-300
references: 9233866
references: N Engl J Med. 2004 Oct 7;351(15):1502-12
references: 15470213
references: J Clin Oncol. 2010 Mar 20;28(9):1489-95
references: 20159823
references: Urology. 2004 May;63(5):940-5
references: 15134985
references: Urol Oncol. 2006 Sep-Oct;24(5):396-402
references: 16962488
references: Clin Cancer Res. 2009 Feb 15;15(4):1504; 1504-5
references: 19228753
references: J Clin Oncol. 1996 Jun;14(6):1756-64
references: 8656243
references: Science. 2005 Oct 28;310(5748):644-8
references: 16254181
references: N Engl J Med. 2010 Jul 29;363(5):411-22
references: 20818862
references: J Clin Oncol. 1997 Aug;15(8):2928-38
references: 9256137
references: Proc Natl Acad Sci U S A. 2010 Sep 28;107(39):16759-65
references: 20823238
references: Clin Cancer Res. 2009 Jan 15;15(2):723-30
references: 19147780
references: Clin Cancer Res. 2010 Nov 1;16(21):5269-76
references: 20978144
references: Science. 2009 May 8;324(5928):787-90
references: 19359544
references: J Clin Oncol. 2004 Mar 15;22(6):1025-33
references: 15020604