Antitumour activity of abiraterone acetate against metastatic castration-resistant prostate cancer progressing after docetaxel and enzalutamide (MDV3100)

被引:298
作者
Loriot, Y. [1 ]
Bianchini, D. [2 ,3 ]
Ileana, E. [1 ]
Sandhu, S. [2 ,3 ]
Patrikidou, A. [1 ]
Pezaro, C. [2 ,3 ]
Albiges, L. [1 ]
Attard, G. [2 ,3 ]
Fizazi, K. [1 ]
De Bono, J. S. [2 ,3 ]
Massard, C. [1 ]
机构
[1] Univ Paris Sud, Dept Canc Med, Inst Gustave Roussy, INSERM 981, Villejuif, France
[2] Royal Marsden NHS Fdn Trust, Sect Med, Sutton, Surrey, England
[3] Inst Canc Res, Sutton, Surrey, England
关键词
CRPC; enzalutamide; abiraterone; hormonal manipulations; ANDROGEN RECEPTOR; INCREASED SURVIVAL; INHIBITION;
D O I
10.1093/annonc/mdt136
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background: Androgen receptor (AR) signalling remains critically important in metastatic castration-resistant prostate cancer (mCRPC) as confirmed by recent phase III trials, showing a survival advantage for abiraterone acetate and enzalutamide (MDV3100). The antitumour activity of abiraterone and prednisolone in patients pre-treated with enzalutamide is as yet unknown. Patients and methods: We investigated the antitumour activity of abiraterone and prednisolone in patients with mCRPC who had progressed following treatment with docetaxel (Taxotere) and enzalutamide. Clinical data were retrospectively analysed for prostate-specific antigen (PSA) and RECIST responses, clinical benefit and survival. Results: Thirty-eight patients were included in the analysis. The median age was 71 years (range 52-84); metastatic sites included bone disease in 37 patients (97%), lymph nodes in 15 patients (39%) and visceral disease in 10 patients (26%). Abiraterone was well tolerated. Three patients (8%) attained a PSA response, defined as >= 50% decline in PSA confirmed after >= 4 weeks, while seven patients (18%) had a >= 30% PSA decline. The median progression-free survival (PFS) was 2.7 months (95% Cl 2.3-4.1). Of the 12 patients assessable radiologically, only 1 (8%) attained a confirmed partial response. Conclusion: Abiraterone and prednisolone have modest antitumour activities in patients with mCRPC pretreated with docetaxel and enzalutamide.
引用
收藏
页码:1807 / 1812
页数:6
相关论文
共 22 条
[1]   Incidence and management of mTOR inhibitor-associated pneumonitis in patients with metastatic renal cell carcinoma [J].
Albiges, L. ;
Chamming's, F. ;
Duclos, B. ;
Stern, M. ;
Motzer, R. J. ;
Ravaud, A. ;
Camus, P. .
ANNALS OF ONCOLOGY, 2012, 23 (08) :1943-1953
[2]   Selective Inhibition of CYP17 With Abiraterone Acetate Is Highly Active in the Treatment of Castration-Resistant Prostate Cancer [J].
Attard, Gerhardt ;
Reid, Alison H. M. ;
A'Hern, Roger ;
Parker, Christopher ;
Oommen, Nikhil Babu ;
Folkerd, Elizabeth ;
Messiou, Christina ;
Molife, L. Rhoda ;
Maier, Gal ;
Thompson, Emilda ;
Olmos, David ;
Sinha, Rajesh ;
Lee, Gloria ;
Dowsett, Mitch ;
Kaye, Stan B. ;
Dearnaley, David ;
Kheoh, Thian ;
Molina, Arturo ;
de Bono, Johann S. .
JOURNAL OF CLINICAL ONCOLOGY, 2009, 27 (23) :3742-3748
[3]   Intratumoral De Novo Steroid Synthesis Activates Androgen Receptor in Castration-Resistant Prostate Cancer and Is Upregulated by Treatment with CYP17A1 Inhibitors [J].
Cai, Changmeng ;
Chen, Sen ;
Ng, Patrick ;
Bubley, Glenn J. ;
Nelson, Peter S. ;
Mostaghel, Elahe A. ;
Marck, Brett ;
Matsumoto, Alvin M. ;
Simon, Nicholas I. ;
Wang, Hongyun ;
Chen, Shaoyong ;
Balk, Steven P. .
CANCER RESEARCH, 2011, 71 (20) :6503-6513
[4]   Reciprocal Feedback Regulation of PI3K and Androgen Receptor Signaling in PTEN-Deficient Prostate Cancer [J].
Carver, Brett S. ;
Chapinski, Caren ;
Wongvipat, John ;
Hieronymus, Haley ;
Chen, Yu ;
Chandarlapaty, Sarat ;
Arora, Vivek K. ;
Le, Carl ;
Koutcher, Jason ;
Scher, Howard ;
Scardino, Peter T. ;
Rosen, Neal ;
Sawyers, Charles L. .
CANCER CELL, 2011, 19 (05) :575-586
[5]   Abiraterone and Increased Survival in Metastatic Prostate Cancer [J].
De Bono, Johann S. ;
Logothetis, Christopher J. ;
Molina, Arturo ;
Fizazi, Karim ;
North, Scott ;
Chu, Luis ;
Chi, Kim N. ;
Jones, Robert J. ;
Goodman, Oscar B., Jr. ;
Saad, Fred ;
Staffurth, John N. ;
Mainwaring, Paul ;
Harland, Stephen ;
Flaig, Thomas W. ;
Hutson, Thomas E. ;
Cheng, Tina ;
Patterson, Helen ;
Hainsworth, John D. ;
Ryan, Charles J. ;
Sternberg, Cora N. ;
Ellard, Susan L. ;
Flechon, Aude ;
Saleh, Mansoor ;
Scholz, Mark ;
Efstathiou, Eleni ;
Zivi, Andrea ;
Bianchini, Diletta ;
Loriot, Yohann ;
Chieffo, Nicole ;
Thian Kheoh ;
Haqq, Christopher M. ;
Scher, Howard I. .
NEW ENGLAND JOURNAL OF MEDICINE, 2011, 364 (21) :1995-2005
[6]   MDV3100 effects on androgen receptor (AR) signaling and bone marrow testosterone concentration modulation: A preliminary report. [J].
Efstathiou, E. ;
Titus, M. A. ;
Tsavachidou, D. ;
Hoang, A. ;
Karlou, M. ;
Wen, S. ;
Troncoso, P. ;
Ashe, R. ;
Berman, C. J. ;
Mohler, J. ;
Logothetis, C. .
JOURNAL OF CLINICAL ONCOLOGY, 2011, 29 (15)
[7]   Effects of Abiraterone Acetate on Androgen Signaling in Castrate-Resistant Prostate Cancer in Bone [J].
Efstathiou, Eleni ;
Titus, Mark ;
Tsavachidou, Dimitra ;
Tzelepi, Vassiliki ;
Wen, Sijin ;
Anh Hoang ;
Molina, Arturo ;
Chieffo, Nicole ;
Smith, Lisa A. ;
Karlou, Maria ;
Troncoso, Patricia ;
Logothetis, Christopher J. .
JOURNAL OF CLINICAL ONCOLOGY, 2012, 30 (06) :637-643
[8]   Estimates of the cancer incidence and mortality in Europe in 2006 [J].
Ferlay, J. ;
Autier, P. ;
Boniol, M. ;
Heanue, M. ;
Colombet, M. ;
Boyle, P. .
ANNALS OF ONCOLOGY, 2007, 18 (03) :581-592
[9]   Abiraterone acetate for treatment of metastatic castration-resistant prostate cancer: final overall survival analysis of the COU-AA-301 randomised, double-blind, placebo-controlled phase 3 study [J].
Fizazi, Karim ;
Scher, Howard I. ;
Molina, Arturo ;
Logothetis, Christopher J. ;
Chi, Kim N. ;
Jones, Robert J. ;
Staffurth, John N. ;
North, Scott ;
Vogelzang, Nicholas J. ;
Saad, Fred ;
Mainwaring, Paul ;
Harland, Stephen ;
Goodman, Oscar B., Jr. ;
Sternberg, Cora N. ;
Li, Jin Hui ;
Kheoh, Thian ;
Haqq, Christopher M. ;
de Bono, Johann S. .
LANCET ONCOLOGY, 2012, 13 (10) :983-992
[10]   Distinct Transcriptional Programs Mediated by the Ligand-Dependent Full-Length Androgen Receptor and Its Splice Variants in Castration-Resistant Prostate Cancer [J].
Hu, Rong ;
Lu, Changxue ;
Mostaghel, Elahe A. ;
Yegnasubramanian, Srinivasan ;
Gurel, Meltem ;
Tannahill, Clare ;
Edwards, Joanne ;
Isaacs, William B. ;
Nelson, Peter S. ;
Bluemn, Eric ;
Plymate, Stephen R. ;
Luo, Jun .
CANCER RESEARCH, 2012, 72 (14) :3457-3462