Management of metastatic castration-resistant prostate cancer: Recent advances

Drugs

Volumn 72, Issue 8, 2012, Pages 1011-1028

  Mukherji, Deborah ^a   Eichholz, Andrew ^a   De Bono, Johann S ^a  

^a INSTITUTE OF CANCER RESEARCH   (United Kingdom)

Author keywords

Abiraterone acetate; Aflibercept; ARN 509; AZD 3514; Bevacizumab; Bicalutamide; Cabazitaxel; Cabozantinib; Calcitriol; Custirsen; Cyproterone; Dasatinib; Docetaxel; EZN 4176; Flutamide; Galeterone; Ipilimumab; Ketoconazole; MDV 3100; Nilutamide; Orteronel; Prednisone

Indexed keywords

4 [3 [4 CYANO 3 (TRIFLUOROMETHYL)PHENYL] 5,5 DIMETHYL 4 OXO 2 THIOXO 1 IMIDAZOLIDINYL] 2 FLUORO N METHYLBENZAMIDE; ABIRATERONE ACETATE; ANDROGEN RECEPTOR; ANDROGEN RECEPTOR ANTAGONIST; BICALUTAMIDE; CABAZITAXEL; CALCITRIOL; CAPECITABINE; CARBOPLATIN; CYPROTERONE ACETATE; CYTOCHROME P450 17; DASATINIB; DOCETAXEL; EPIRUBICIN; ESTRAMUSTINE; FLUTAMIDE; GALETERONE; IPILIMUMAB; KETOCONAZOLE; MITOXANTRONE; NAVELBINE; NILUTAMIDE; ORTERONEL; PHOSPHATIDYLINOSITOL 3,4,5 TRISPHOSPHATE 3 PHOSPHATASE; PLACEBO; PREDNISONE; PROSTATE SPECIFIC ANTIGEN; SIPULEUCEL T; UNCLASSIFIED DRUG; UNINDEXED DRUG; VT 464;

ANGIOGENESIS; ANTINEOPLASTIC ACTIVITY; APOPTOSIS; ARTICLE; BLOOD PRESSURE REGULATION; BONE METASTASIS; CANCER CHEMOTHERAPY; CANCER GRADING; CANCER GROWTH; CANCER PATIENT; CANCER RADIOTHERAPY; CANCER RESISTANCE; CANCER STAGING; CANCER SURVIVAL; CASTRATION; CASTRATION RESISTANT PROSTATE CANCER; CIRCULATING TUMOR CELL; CLINICAL PRACTICE; COMPUTER ASSISTED EMISSION TOMOGRAPHY; CYTOTOXICITY; DNA BINDING; DRUG COST; DRUG DEVELOPMENT; DRUG DOSE COMPARISON; DRUG DOSE REDUCTION; DRUG SAFETY; DRUG TOLERABILITY; FATIGUE; FEBRILE NEUTROPENIA; FOLLOW UP; HUMAN; IMMUNOTHERAPY; IN VIVO STUDY; LIVER TOXICITY; LOW DRUG DOSE; METASTASIS; NEUROTOXICITY; NEUTROPENIA; NUCLEAR MAGNETIC RESONANCE IMAGING; ORCHIECTOMY; PERIPHERAL BLOOD MONONUCLEAR CELL; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PROGRESSION FREE SURVIVAL; PROSTATE CANCER; SEIZURE; SIGNAL TRANSDUCTION; TREATMENT DURATION; TREATMENT RESPONSE;

ANTINEOPLASTIC AGENTS; CLINICAL TRIALS AS TOPIC; HUMANS; IMMUNOTHERAPY; MALE; NEOPLASM METASTASIS; ORCHIECTOMY; PROSTATIC NEOPLASMS; RANDOMIZED CONTROLLED TRIALS AS TOPIC;

EID: 84861418291     PISSN: 00126667     EISSN: 11791950     Source Type: Journal    
DOI: 10.2165/11633360-000000000-00000     Document Type: Article

References (117)

1. Jemal A, Siegel R, Xu J, et al. Cancer statistics, 2010. CA Cancer J Clin 2010 Sep 1; 60 (5): 277-300
2. La Vecchia C, Bosetti C, Lucchini F, et al. Cancer mortality in Europe, 2000-2004, and an overview of trends since 1975. Ann Oncol 2010 Jun; 21 (6): 1323-60
3. Kantoff PW, Higano CS, Shore ND, et al. Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med 2010 Jul 29; 363 (5): 411-22
4. de Bono JS, Oudard S, Ozguroglu M, et al. Prednisone plus cabazitaxel or mitoxantrone for metastatic castrationresistant prostate cancer progressing after docetaxel treatment: a randomised open-label trial. Lancet 2010 Oct 2; 376 (9747): 1147-54
5. de Bono JS, Logothetis CJ, Molina A, et al. Abiraterone and increased survival in metastatic prostate cancer. N Engl J Med 2011 May 26; 364 (21): 1995-2005
6. Parker C, Heinrich D, O'Sullivan JM, et al. Overall survival benefit of radium-223 chloride (Alpharadin-) in the treatment of patients with symptomatic bone metastases in castration-resistant prostate cancer (CRPC): a phase III randomized trial (ALSYMPCA). European Multidisciplinary Cancer Congress; 2011 Sep 23-27; Stockholm
7. Scher HI FK, Saad F, Taplin ME, et al., for the AFFIRM Investigators. Effect of MDV3100, an androgen receptor signaling inhibitor (ARSI), on overall survival in patients with prostate cancer postdocetaxel: results from the phase III AFFIRM study. J Clin Oncol 2012; 30 Suppl. 5: LBA 1
8. Fleming MT, Morris MJ, Heller G, et al. Post-therapy changes in PSA as an outcome measure in prostate cancer clinical trials.Nat Clin PractOncol 2006 Dec; 3 (12): 658-67 (Pubitemid 44843124)
9. de Bono JS, Scher HI, Montgomery RB, et al. Circulating tumor cells predict survival benefit from treatment in metastatic castration-resistant prostate cancer. Clin Cancer Res 2008 Oct 1; 14 (19): 6302-9
10. Scher HI, Jia X, de Bono JS, et al. Circulating tumour cells as prognostic markers in progressive, castration-resistant prostate cancer: a reanalysis of IMMC38 trial data. Lancet Oncol 2009 Mar; 10 (3): 233-9
11. Olmos D, Arkenau HT, Ang JE, et al. Circulating tumour cell (CTC) counts as intermediate end points in castrationresistant prostate cancer (CRPC): a single-centre experience. Ann Oncol 2009 Jan; 20 (1): 27-33
12. Bubley GJ, Carducci M, Dahut W, et al. Eligibility and response guidelines for phase II clinical trials in androgenindependent prostate cancer: recommendations from the Prostate-Specific Antigen Working Group. J Clin Oncol 1999 Nov; 17 (11): 3461-7 (Pubitemid 29517916)
13. Therasse P, Arbuck SG, Eisenhauer EA, et al. New guidelines to evaluate the response to treatment in solid tumors. European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada. J Natl Cancer Inst 2000 Feb 2; 92 (3): 205-16 (Pubitemid 30099779)
14. Scher HI, Halabi S, Tannock I, et al. Design and end points of clinical trials for patients with progressive prostate cancer and castrate levels of testosterone: recommendations of the Prostate Cancer Clinical Trials Working Group. J Clin Oncol 2008 Mar 1; 26 (7): 1148-59
15. Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 2009 Jan; 45 (2): 228-47
16. Ryan CJ, Shah S, Efstathiou E, et al. Phase II study of abiraterone acetate in chemotherapy-naive metastatic castration-resistant prostate cancer displaying bone flare discordant with serologic response. Clin Cancer Res 2011 Jul 15; 17 (14): 4854-61
17. Messiou C, Collins DJ, Giles S, et al. Assessing response in bone metastases in prostate cancer with diffusion weighted MRI. Eur Radiol 2011 Oct; 21 (10): 2169-77
18. Picchio M, Spinapolice EG, Fallanca F, et al. [11C]Choline PET/CT detection of bone metastases in patients with PSA progression after primary treatment for prostate cancer: comparison with bone scintigraphy. Eur J Nucl Med Mol Imaging 2012 Jan; 39 (1): 13-26
19. Brown JE, Sim S. Evolving role of bone biomarkers in castration-resistant prostate cancer. Neoplasia 2010 Sep; 12 (9): 685-96
20. Armstrong AJ, Garrett-Mayer E, Ou Yang YC, et al. Prostate-specific antigen and pain surrogacy analysis in metastatic hormone-refractory prostate cancer. J Clin Oncol 2007 Sep 1; 25 (25): 3965-70 (Pubitemid 47477275)
21. Hayes DF, Cristofanilli M, Budd GT, et al. Circulating tumor cells at each follow-up time point during therapy of metastatic breast cancer patients predict progression-free and overall survival. Clin CancerRes 2006 Jul 15; 12 (14 Pt 1): 4218-24
22. Tol J, Koopman M, Miller MC, et al. Circulating tumour cells early predict progression-free and overall survival in advanced colorectal cancer patients treated with chemotherapy and targeted agents. Ann Oncol 2010 May; 21 (5): 1006-12
23. Scher HI, Heller G, Molina AS, et al. Evaluation of circulating tumor cell (CTC) enumeration as an efficacy response biomarker of overall survival (OS) in metastatic castration-resistant prostate cancer (mCRPC): planned final analysis (FA) of COU-AA-301, a randomized double-blind, placebo-controlled phase III study of abiraterone acetate (AA) plus low-dose prednisone (P) post docetaxel [abstract LBA4517]. J Clin Oncol 2011; 29 Suppl.
24. Danila DC, Fleisher M, Scher HI. Circulating tumor cells as biomarkers in prostate cancer. Clin Cancer Res 2011 Jun 15; 17 (12): 3903-2
25. Attard G, Swennenhuis JF, Olmos D, et al. Characterization of ERG, AR and PTEN gene status in circulating tumor cells from patients with castration-resistant prostate cancer. Cancer Res 2009 Apr 1; 69 (7): 2912-8
26. Darshan MS, Loftus MS, Thadani-Mulero M, et al. Taxane-induced blockade to nuclear accumulation of the androgen receptor predicts clinical responses in metastatic prostate cancer. Cancer Res 2011 Sep 15; 71 (18): 6019-29
27. Small EJ, Halabi S, Dawson NA, et al. Antiandrogen withdrawal alone or in combination with ketoconazole in androgen-independent prostate cancer patients: a phase III trial (CALGB 9583). J Clin Oncol 2004 Mar 15; 22 (6): 1025-33 (Pubitemid 41095034)
28. O'Donnell A, Judson I, Dowsett M, et al. Hormonal impact of the 17alpha-hydroxylase/C(17,20)-lyase inhibitor abiraterone acetate (CB7630) in patients with prostate cancer. Br J Cancer 2004 Jun 14; 90 (12): 2317-25 (Pubitemid 38961894)
29. Attard G, Reid AH, A'Hern R, et al. Selective inhibition of CYP17 with abiraterone acetate is highly active in the treatment of castration-resistant prostate cancer. J Clin Oncol 2009 Aug 10; 27 (23): 3742-8
30. Ryan CJ, Smith MR, Fong L, et al. Phase I clinical trial of the CYP17 inhibitor abiraterone acetate demonstrating clinical activity in patients with castration-resistant prostate cancer who received prior ketoconazole therapy. J Clin Oncol 2010 Mar 20; 28 (9): 1481-8
31. Cougar Biotechnology, Inc. Abirateron acetate in asymptomatic or mildly symptomatic patients with metastatic castration-resistant prostate cancer [ClinicalTrials.gov identifierNCT00887198].USNational Institutes ofHealth, ClinicalTrials.gov [online]. Available from URL: http://www.clinicaltrials.gov [Accessed 2012 Apr 4]
32. Johnson & Johnson. Study unblinded: ZYTIGA (abiraterone acetate) plus prednisone for asymptomatic or mildly symptomatic chemotherapy-naive patients with metastatic castration-resistant prostate cancer [media release]. 2012 [online]. Available from URL: http://www.jnj. com/connect/news/all/study- unblinded-zytiga-abirateroneacetate-plus-prednisone-for-asymptomatic-or-mildly- symp tomatic-chemotherapy-naive-patients-with-metastatic-castra tion-resistant-prostate-cancer [Accessed 2012 Mar 17]
33. Cougar Biotechnology, Inc. Neo-adjuvant abiraterone + luteinizing hormone-releasing hormone (LHRH) versus LHRH in prostate cancer [ClinicalTrials.gov identifier NCT01088529]. US National Institutes of Health, ClinicalTrials. gov [online]. Available from URL: http://www. clinicaltrials.gov [Accessed 2012 Apr 4]
34. Cougar Biotechnology, Inc. Neoadjuvant abiraterone acetate plus leuprolide acetate in men with localized high risk prostate cancer [ClinicalTrials.gov identifierNCT00924469]. US National Institutes of Health, ClinicalTrials.gov [online]. Available from URL: http://www.clinicaltrials.gov [Accessed 2012 Apr 4]
35. Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium. Abiraterone acetate, prednisone and leuprolide acetate or goserelin before and during radiation therapy in treating patients with localized or locally advanced prostate cancer [ClinicalTrials. gov identifier NCT01023061]. US National Institutes of Health, ClinicalTrials.gov [online]. Available from URL: http://www.clinicaltrials.gov [Accessed 2012 Apr 4]
36. Agus DB SM, Shevrin DH, Hart L, et al. Safety, efficacy, and pharmacodynamics of the investigational agent orteronel (TAK-700) in metastatic castration-resistant prostate cancer (mCRPC): updated data from a phase I/II study [abstract no. 98]. J Clin Oncol 2012; 30 Suppl. 5
37. Millennium Pharmaceuticals, Inc. Study comparing orteronel plus prednisone in patients with chemotherapy-naïve metastatic castration-resistant prostate cancer [Clinical-Trials.gov identifier NCT01193244]. US National Institutes of Health, ClinicalTrials.gov [online]. Available from URL: http://www.clinicaltrials.gov [Accessed 2012 Apr 4]
38. Millennium Pharmaceuticals, Inc. Study comparing orteronel plus prednisone in patients with metastatic castration-resistant prostate cancer [ClinicalTrials.gov identifier NCT01193257]. US National Institutes of Health, Clinical-Trials.gov [online]. Available from URL: http://www.cli nicaltrials.gov [Accessed 2012 Apr 4]
39. Millennium Pharmaceuticals, Inc. Safety and efficacy study of TAK-700 in patients with nonmetastatic castrationresistant prostate cancer and a rising prostate-specific antigen [ClinicalTrials.gov identifier NCT01046916]. US National Institutes of Health, ClinicalTrials.gov [online]. Available from URL: http://www.clinicaltrials.gov [Accessed 2012 Apr 4]
40. Millennium Pharmaceuticals, Inc. Study of TAK-700 in combination with docetaxel and prednisone in men with metastatic castration-resistant prostate cancer [Clinical-Trials.gov identifier NCT01084655]. US National Institutes of Health, ClinicalTrials.gov [online]. Available from URL: http://www. clinicaltrials.gov [Accessed 2012 Apr 4]
41. Tokai Pharmaceuticals. ARMOR1: study of TOK-001 to treat castration resistant prostate cancer [Clinical-Trials.gov identifier NCT00959959]. US National Institutes of Health, ClinicalTrials.gov [online]. Available from URL: http://www.clinicaltrials.gov [Accessed 2012 Apr 4]
42. Aragon Pharmaceuticals, Inc. Safety, pharmacokinetic and proof-of-concept study of ARN-509 in castration-resistant prostate cancer (CRPC) [ClinicalTrials.gov identifier NCT01171898]. US National Institutes of Health, ClinicalTrials. gov [online]. Available from URL: http://www.clinicaltrials.gov [Accessed 2012 Apr 4]
43. AstraZeneca. Open label prostate cancer study [Clinical-Trials.gov identifierNCT01162395].USNational Institutes of Health, ClinicalTrials.gov [online]. Available fromURL: http://www.clinicaltrials.gov [Accessed 2012 Apr 4]
44. Enzon Pharmaceuticals, Inc.A phase 1a/1b study to evaluate the safety of EZN-4176, in adult patients with castrationresistant prostate cancer [ClinicalTrials.gov identifier NCT01337518]. US National Institutes of Health, ClinicalTrials. gov [online]. Available from URL: http://www.clinicaltrials.gov [Accessed 2012 Apr 4]
45. Tran C, Ouk S, Clegg NJ, et al. Development of a secondgeneration antiandrogen for treatment of advanced prostate cancer. Science 2009 May 8; 324 (5928): 787-90
46. Scher HI, Beer TM, Higano CS, et al. Antitumour activity of MDV3100 in castration-resistant prostate cancer: a phase 1-2 study. Lancet 2010 Apr 24; 375 (9724): 1437-46
47. Medivation, Inc. A safety and efficacy study or oral MDV3100 in chemotherapy-naïve patients with progressive metastatic prostate cancer [ClinicalTrials.gov identifier NCT01212991]. US National Institutes of Health, ClinicalTrials.gov [online]. Available from URL: http://www.clinicaltrials.gov [Accessed 2012 Apr 4]
48. Astellas Pharma Inc. A study to test ifMDV3100 is effective and safe prostate cancer patients who have never had hormone therapy [ClinicalTrials.gov identifier NCT01302041]. US National Institutes of Health, ClinicalTrials.gov [online]. Available from URL: http://www.clinicaltrials.gov [Accessed 2012 Apr 4]
49. Astellas Pharma Inc. A study of MDV3100 versus bicalutamide in castrate men with metastatic prostate cancer [ClinicalTrials.gov identifier NCT01288911]. US National Institutes of Health, ClinicalTrials.gov [online]. Available from URL: http://www.clinicaltrials.gov [Accessed 2012 Apr 4]
50. Tannock IF, de Wit R, Berry WR, et al. Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer.NEngl JMed 2004 Oct 7; 351 (15): 1502-12
51. Petrylak DP, Tangen CM, Hussain MH, et al. Docetaxel and estramustine compared with mitoxantrone and prednisone for advanced refractory prostate cancer. N Engl J Med 2004 Oct 7; 351 (15): 1513-20 (Pubitemid 39315318)
52. Beer TM, Ryan CW, Venner PM, et al. Double-blinded randomized study of high-dose calcitriol plus docetaxel compared with placebo plus docetaxel in androgenindependent prostate cancer: a report from the ASCENT Investigators. J Clin Oncol 2007 Feb 20; 25 (6): 669-74 (Pubitemid 350002922)
53. Scher HI, Chi KN, De Wit R, et al. Docetaxel (D) plus high-dose calcitriol versus D plus prednisone (P) for patients (Pts) with progressive castration-resistant prostate cancer (CRPC): results from the phase III ASCENT2 trial [abstract 4509]. J Clin Oncol 2010; 28 (15 Suppl.)
54. Sanofi-Aventis. Cabazitaxel at 20mg/m2 compared to 25mg/m2 with prednisone for the treatment of metastatic castration resistant prostate cancer (PROSELICA) [ClinicalTrials.-gov identifier: NCT01308580]. US National Institutes of Health, ClinicalTrials.gov [online]. Available from URL: http://www.clinicaltrials.gov [Accessed 2012 Apr 16]
55. Small EJ, Fratesi P, Reese DM, et al. Immunotherapy of hormone-refractory prostate cancer with antigen-loaded dendritic cells. J Clin Oncol 2000 Dec 1; 18 (23): 3894-903
56. Small EJ, Schellhammer PF, Higano CS, et al. Placebocontrolled phase III trial of immunologic therapy with sipuleucel-T (APC8015) in patients with metastatic, asymptomatic hormone refractory prostate cancer. J Clin Oncol 2006 Jul 1; 24 (19): 3089-94 (Pubitemid 46638945)
57. Higano CS, Schellhammer PF, Small EJ, et al. Integrated data from 2 randomized, double-blind, placebocontrolled, phase 3 trials of active cellular immunotherapy with sipuleucel-T in advanced prostate cancer. Cancer 2009 Aug 15; 115 (16): 3670-9
58. Nabhan C, Gomella LG, DeVries T, et al. An analysis to quantify the overall survival (OS) benefit of sipuleucel-T accounting for the crossover in the control arm of the IMPACT study [abstract no. 144]. J Clin Oncol 2012; 30 Suppl. 5
59. Longo DL. New therapies for castration-resistant prostate cancer. N Engl J Med 2010 Jul 29; 363 (5): 479-81
60. Figg WD, Hussain MH, Gulley JL, et al. A double-blind randomized crossover study of oral thalidomide versus placebo for androgen dependent prostate cancer treated with intermittent androgen ablation. J Urol 2009 Mar; 181 (3): 1104-13; discussion 13
61. Small EJ, Demkow T, Gerritsen WR, et al. A phase III trial of GVAX immunotherapy for prostate cancer in combination with docetaxel versus docetaxel plus prednisone in symptomatic, castration-resistant prostate cancer (CRPC). ASCO Genitourinary Cancers Symposium; 2009 Feb 26-28; Orlando (FL)
62. Kantoff PW, Schuetz TJ, Blumenstein BA, et al. Overall survival analysis of a phase II randomized controlled trial of a Poxviral-based PSA-targeted immunotherapy in metastatic castration-resistant prostate cancer. J Clin Oncol 2010 Mar 1; 28 (7): 1099-105
63. BN ImmunoTherapeutics. A phase 3 efficacy study of a recombinant vaccinia virus vaccine to treat metastatic prostate cancer (Prospect). [ClinicalTrials.gov identifier: NCT01322490]. US National Institutes of Health, ClinicalTrials. gov [online]. Available from URL: http://www.clinicaltrials.gov [Accessed 2012 Apr 16]
64. McNeel DG, Dunphy EJ, Davies JG, et al. Safety and immunological efficacy of a DNA vaccine encoding prostatic acid phosphatase in patients with stage D0 prostate cancer. J Clin Oncol 2009 Sep 1; 27 (25): 4047-54
65. Nanus DM, Milowsky MI, Kostakoglu L, et al. Clinical use of monoclonal antibody HuJ591 therapy: targeting prostate specific membrane antigen. JUrol 2003; 170 (6 Pt 2): S84-8
66. Bander NH, Milowsky MI, Nanus DM, et al. Phase I trial of 177lutetium-labeled J591, a monoclonal antibody to prostate-specific membrane antigen, in patients with androgen-independent prostate cancer. J Clin Oncol 2005 Jul 20; 23 (21): 4591-601 (Pubitemid 46224061)
67. Galsky MD, Eisenberger M, Moore-Cooper S, et al. Phase I trial of the prostate-specific membrane antigen-directed immunoconjugate MLN2704 in patients with progressive metastatic castration-resistant prostate cancer. J Clin Oncol 2008 May 1; 26 (13): 2147-54
68. Progenics Pharmaceuticals, Inc. Prostate-specific membrane antigen antibody-drug conjugate in subjects with prostate cancer [ClinicalTrials.gov identifier: NCT01414283]. US National Institutes of Health, ClinicalTrials.gov [online]. Available from URL: http://www.clinicaltrials.gov [Accessed 2012 Apr 16]
69. Slovin SF BT, Higano CS. Initial phase II experience of ipilimumab (IPI) alone and in combination with radiotherapy (XRT) in patients with metastatic castration resistant prostate cancer (mCRPC) [abstract no. 5138]. J Clin Oncol 2009; 27 (15 Suppl.)
70. Bristol-Myers Squibb. Study of immunotherapy to treat advanced prostate cancer [ClinicalTrials.gov identifier: NCT00861614]. US National Institutes of Health, ClinicalTrials. gov [online]. Available from URL: http://www. clinicaltrials.gov [Accessed 2012 Apr 16]
71. Bristol-Myers Squibb. Phase 3 study of immunotherapy to treat advanced prostate cancer [ClinicalTrials.gov identifier: NCT01057810]. US National Institutes of Health, ClinicalTrials.gov [online]. Available from URL: http://www.clinicaltrials.gov [Accessed 2012 Apr 17]
72. Brahmer JR, Drake CG, Wollner I, et al. Phase I study of single-agent anti-programmed death-1 (MDX-1106) in refractory solid tumors: safety, clinical activity, pharmacodynamics, and immunologic correlates. J Clin Oncol 2010 Jul 1; 28 (19): 3167-75
73. Fox WD, Higgins B, Maiese KM, et al. Antibody to vascular endothelial growth factor slows growth of an androgen-independent xenograft model of prostate cancer. Clin Cancer Res 2002 Oct; 8 (10): 3226-31 (Pubitemid 35155035)
74. Kelly WK, Halabi S, Carducci MA, et al. A randomized, double-blind, placebo-controlled phase III trial comparing doectaxel, prednisone and placebo with docetaxel, prednisone and bevacizumab in men with metastatic castration-reesitant prostate cancer (mCRPC): survival results of CALGB 90401 [abstract no. LBA4511]. J Clin Oncol 2010; 28 (7s)
75. Sanofi-Aventis. Aflibercept in combination with docetaxel in metastatic androgen independent prostate cancer (VENICE) [ClinicalTrials.gov identifier: NCT00519285]. US National Institutes of Health, ClinicalTrials.gov [online]. Available from URL: http://www.clinicaltrials.gov [Accessed 2012 Apr 17]
76. Ning YM, Gulley JL, Arlen PM, et al. Phase II trial of bevacizumab, thalidomide, docetaxel, and prednisone in patients with metastatic castration-resistant prostate cancer. J Clin Oncol 2010 Apr 20; 28 (12): 2070-6
77. Celgene Corporation. Study to evaluate safety and effectiveness of lenalidomide in combination with docetaxel and prednisone for patients with castrate-resistant prostate cancer (Mainsail) [ClinicalTrials.gov identifier: NCT00988208]. US National Institutes of Health, ClinicalTrials. gov [online]. Available from URL: http://www.clinicaltrials.gov [Accessed 2012 Apr 17]
78. Celgene. Celgene will discontinue phase III MAINSAIL(R) trial in castrate-resistant prostate cancer [media release]. 2011 [online]. Available from URL: http://ir.celgene.com/phoenix.zhtml?c=111960&p=irol- newsArticle&ID=1633148& highlight= [Accessed 2012 Mar 21]
79. Pili R, Haggman M, Stadler WM, et al. Phase II randomized, double-blind, placebo-controlled study of tasquinimod in men with minimally symptomatic metastatic castrateresistant prostate cancer. J Clin Oncol 2011; 29 (30): 4022-8
80. Active Biotech AB. A study of tasquinimod in men with metastatic castrate resistant prostate cancer [Clinical-Trials.gov identifier: NCT01234311]. US National Institutes of Health, ClinicalTrials.gov [online]. Available from URL: http://www.clinicaltrials.gov [Accessed 2012 Apr 17]
81. Pfizer. Sunitinib plus prednisone in patients with metastatic castration-resistant prostate cancer after failure of docetaxel chemotherapy (SUN 1120) [ClinicalTrials.gov identifier: NCT00676650]. US National Institutes of Health, ClinicalTrials.gov [online]. Available from URL: http://www. clinicaltrials.gov [Accessed 2012 Apr 17]
82. Aragon-Ching JB, Jain L, Gulley JL, et al. Final analysis of a phase II trial using sorafenib for metastatic castrationresistant prostate cancer. BJUInt 2009 Jun; 103 (12): 1636-40
83. Hussain MRS, Sweeney C, Corn PG, et al. Cabozantinib (XL184) in metastatic castration-resistant prostate cancer (mCRPC): results from a phase II randomized discontinuation trial [abstract no. 4516]. J Clin Oncol 2011; 29 Suppl.
84. Lockhart AC, Rothenberg ML, Dupont J, et al. Phase I study of intravenous vascular endothelial growth factor trap, aflibercept, in patients with advanced solid tumors. J Clin Oncol 2010 Jan 10; 28 (2): 207-14
85. Isambert N, Freyer G, Zanetta S et al. A phase I dose escalation and pharmacokinetic (PK) study of intravenous aflibercept (VEGFtrap) plus docetaxel (D) in patients (pts) with advanced solid tumors:preliminary results. J Clin Oncol 2008; 28 Suppl. 18s
86. Sonpavde G, Periman PO, Bernold D, et al. Sunitinib malate for metastatic castration-resistant prostate cancer following docetaxel-based chemotherapy. Ann Oncol 2010 Feb; 21 (2): 319-24
87. Dror Michaelson M, Regan MM, Oh WK, et al. Phase II study of sunitinib in men with advanced prostate cancer. Ann Oncol 2009 May; 20 (5): 913-20
88. Michaelson MD, Oudard S, Ou Y, et al. Randomized, placebo-controlled, phase III trial of sunitinib in combination with prednisone (SU+P) versus prednisone (P) alone in men with progressive metastatic castrationresistant prostate cancer (mCRPC) [abstract no. 4515]. J Clin Oncol 2011; 29 Suppl.
89. Exelixis. Exelixis' cabozantinib meets primary endpoint in phase 3 clinical trial for medullary thyroid cancer [media release]. 2011 Oct 24 [online]. Available from URL: http://www.exelixis.com/investors-media/press- releases [Accessed 2012 Mar 17]
90. Chen M, Pratt CP, Zeeman ME, et al. Identification of PHLPP1 as a tumor suppressor reveals the role of feedback activation in PTEN-mutant prostate cancer progression. Cancer Cell 2011 Aug 16; 20 (2): 173-86
91. Higano C, Alumkal J, Ryan CJ et al. A phase II study evaluating the efficacy and safety of single agent IMC A12, a monoclonal antibody (Mab) against the insulinlike growth factor-1 receptor (IGF-1R), as monotherapy in patients with metastatic, asymptomatic castrationresistant prostate cancer (CRPC) [abstract no. 5142]. J Clin Oncol 2009; 27 (15 Suppl.)
92. Pfizer. Study of CP-751,871 in combination with docetaxel and prednisone in patients with hormone insensitive prostate cancer (HRPC) [ClinicalTrials.gov identifier: NCT00313781]. US National Institutes of Health, ClinicalTrials. gov [online]. Available from URL: http://www.clinicaltrials.gov [Accessed 2012 Apr 17]
93. Yu EY, Wilding G, Posadas E, et al. Phase II study of dasatinib in patients with metastatic castration-resistant prostate cancer. Clin Cancer Res 2009 Dec 1; 15 (23): 7421-8
94. Yu EY, Massard C, Gross ME, et al. Once-daily dasatinib: expansion of phase II study evaluating safety and efficacy of dasatinib in patients with metastatic castration-resistant prostate cancer. Urology 2011 May; 77 (5): 1166-71
95. Araujo J, Armstrong AJ, Braud EL, et al. Dasatinib and docetaxel combination treatment for patients with castration-resistant progressive prostate cancer: a phase I/II study (CA180086) [abstract no. 5061]. J Clin Oncol 2009; 27 (15 Suppl.)
96. Bristol-Myers Squibb. Randomized study comparing docetaxel plus dasatinib to docetaxel plus placebo in castrationresistant prostate cancer (READY) [ClinicalTrials.gov identifier: NCT00744497]. US National Institutes of Health, ClinicalTrials.gov [online]. Available from URL: http://www.clinicaltrials.gov [Accessed 2012 Apr 17]
97. Chi KN, Hotte SJ, Yu EY, et al. Randomized phase II study of docetaxel and prednisone with or without OGX-011 in patients with metastatic castration-resistant prostate cancer. J Clin Oncol 2010 Sep 20; 28 (27): 4247-54
98. Morgan TM, Koreckij TD, Corey E. Targeted therapy for advanced prostate cancer: inhibition of the PI3K/Akt/mTORpathway. Curr Cancer Drug Targets 2009 Mar; 9 (2): 237-49
99. Gray IC, Stewart LM, Phillips SM, et al. Mutation and expression analysis of the putative prostate tumour-suppressor gene PTEN. Br J Cancer 1998 Nov; 78 (10): 1296-300 (Pubitemid 28495240)
100. Hodgson MC, Shao LJ, Frolov A, et al. Decreased expression and androgen regulation of the tumor suppressor gene INPP4B in prostate cancer. Cancer Res 2011 Jan 15; 71 (2): 572-82
101. Baselga J, Campone M, Piccart M, et al. Everolimus in postmenopausal hormone-receptor-positive advanced breast cancer. N Engl J Med 2012; 366 (6): 520-9
102. Carver BS, Chapinski C, Wongvipat J, et al. Reciprocal feedback regulation of PI3K and androgen receptor signaling in PTEN-deficient prostate cancer. Cancer Cell 2011 May 17; 19 (5): 575-86
103. de Bono JS, Bellmunt J, Attard G, et al. Open-label phase II study evaluating the efficacy and safety of two doses of pertuzumab in castrate chemotherapy-naive patients with hormone-refractory prostate cancer. J Clin Oncol 2007 Jan 20; 25 (3): 257-62 (Pubitemid 350003013)
104. Fizazi K. The role of Src in prostate cancer. Ann Oncol 2007 Nov; 18 (11): 1765-73 (Pubitemid 350119560)
105. Sanjay A, Houghton A, Neff L, et al. Cbl associates with Pyk2 and Src to regulate Src kinase activity, alpha(v)beta( 3) integrin-mediated signaling, cell adhesion, and osteoclast motility. J Cell Biol 2001 Jan 8; 152 (1): 181-95 (Pubitemid 32102446)
106. Banerji U. Heat shock protein 90 as a drug target: some like it hot. Clin Cancer Res 2009 Jan 1; 15 (1): 9-14
107. Saporita AJ, Ai J, Wang Z. The Hsp90 inhibitor, 17-AAG, prevents the ligand-independent nuclear localization of androgen receptor in refractory prostate cancer cells. Prostate 2007 Apr 1; 67 (5): 509-20 (Pubitemid 46536944)
108. Heath EI, Hillman DW, Vaishampayan U, et al. A phase II trial of 17-allylamino-17-demethoxygeldanamycin in patients with hormone-refractory metastatic prostate cancer. Clin Cancer Res 2008 Dec 1; 14 (23): 7940-6
109. Miyake H, Chi KN, Gleave ME. Antisense TRPM-2 oligodeoxynucleotides chemosensitize human androgenindependent PC-3 prostate cancer cells both in vitro and in vivo. Clin Cancer Res 2000 May; 6 (5): 1655-63 (Pubitemid 30305057)
110. Teva Pharmaceutical Industries. Comparison of docetaxel/prednisone to docetaxel/prednisone in combination with OGX-011 in men with prostate cancer (SYNERGY) [ClinicalTrials.gov identifier: NCT01188187]. US National Institutes of Health, ClinicalTrials.gov [online]. Available from URL: http://www. clinicaltrials.gov [Accessed 2012 Apr 17]
111. OncoGenex Technologies. A study evaluating the pain palliation benefit of adding custirsen to docetaxel retreatment of cabazitaxel as second line therapy in men with metastatic castrate resistant prostate cancer (mCRPC) [ClinicalTrials.gov identifier: NCT01083615]. US National Institutes of Health, ClinicalTrials.gov [online]. Available from URL: http://www.clinicaltrials.gov [Accessed 2012 Apr 17]
112. Saad F, Gleason DM, Murray R, et al. Long-term efficacy of zoledronic acid for the prevention of skeletal complications in patients with metastatic hormone-refractory prostate cancer. J Natl Cancer Inst 2004 Jun 2; 96 (11): 879-82 (Pubitemid 38807610)
113. Fizazi K, Beuzeboc P, Lumbroso J, et al. Phase II trial of consolidation docetaxel and samarium-153 in patients with bone metastases from castration-resistant prostate cancer. J Clin Oncol 2009 May 20; 27 (15): 2429-35
114. Tu SM, Millikan RE, Mengistu B, et al. Bone-targeted therapy for advanced androgen-independent carcinoma of the prostate: a randomised phase II trial. Lancet 2001 Feb 3; 357 (9253): 336-41 (Pubitemid 32128538)
115. Murphy WM, Soloway MS, Barrows GH. Pathologic changes associated with androgen deprivation therapy for prostate cancer. Cancer 1991 Aug 15; 68 (4): 821-8
116. Fizazi K, Carducci M, Smith M, et al. Denosumab versus zoledronic acid for treatment of bone metastases in men with castration-resistant prostate cancer: a randomised, double-blind study. Lancet 2011 Mar 5; 377 (9768): 813-22
117. AMGEN. Phase 3 data demonstrate XGEVA(TM) (Denosumab) is first bone targeted therapy to prevent spread of cancer to the bone inmen with advanced prostate cancer [media release]. 2011 Aug 21 [online]. Available fromURL: http://wwwext.amgen.com/media/media-pr-detail.jsp?year= 2011&releaseID= 1564774 [Accessed 2012 Mar 17]