Antitumour activity of enzalutamide (MDV3100) in patients with metastatic castration-resistant prostate cancer (CRPC) pre-treated with docetaxel and abiraterone

被引:194
作者
Bianchini, D. [1 ,2 ]
Lorente, D. [1 ,2 ]
Rodriguez-Vida, A. [3 ]
Omlin, A. [1 ,2 ]
Pezaro, C. [1 ,2 ]
Ferraldeschi, R. [1 ,2 ]
Zivi, A. [1 ,2 ]
Attard, G. [1 ,2 ]
Chowdhury, S. [3 ]
de Bono, J. S. [1 ,2 ]
机构
[1] Royal Marsden NHS Fdn Trust, Inst Canc Res, Prostate Canc Targeted Therapy Grp, Sutton SM2 5PT, Surrey, England
[2] Royal Marsden NHS Fdn Trust, Inst Canc Res, Drug Dev Unit, Sutton SM2 5PT, Surrey, England
[3] Guys & St Thomas NHS Fdn Trust, London, England
关键词
Abiraterone; Enzalutamide; Castration resistant prostate cancer; Hormone therapy; Androgen receptor targeting; ANDROGEN RECEPTOR; INCREASED SURVIVAL; ACETATE; CELLS;
D O I
10.1016/j.ejca.2013.08.020
中图分类号
R73 [肿瘤学];
学科分类号
100214 [肿瘤学];
摘要
Background: The new generation anti-androgen enzalutamide and the potent CYP17 inhibitor abiraterone have both demonstrated survival benefits in patients with metastatic castration-resistant prostate cancer (CRPC) progressing after docetaxel. Preliminary data on the antitumour activity of abiraterone after enzalutamide have suggested limited activity. The antitumour activity and safety of enzalutamide after abiraterone in metastatic CRPC patients is still unknown. Patients and Methods: We retrospectively identified patients treated with docetaxel and abiraterone prior to enzalutamide to investigate the activity and safety of enzalutamide in a more advanced setting. Prostate specific antigen (PSA), radiological and clinical assessments were analysed. Results: 39 patients with metastatic CRPC were identified for this analysis (median age 70 years, range: 54-85 years). Overall 16 patients (41%) had a confirmed PSA decline of at least 30%. Confirmed PSA declines of >= 50% and >= 90% were achieved in 5/39 (12.8%) and 1/39 (2.5%) respectively. Of the 15 patients who responded to abiraterone, two (13.3%) also had a confirmed >= 50% PSA decline on subsequent enzalutamide. Among the 22 abiraterone-refractory patients, two (9%) achieved a confirmed >= 50% PSA decline on enzalutamide. Conclusion: Our preliminary case series data suggest limited activity of enzalutamide in the post-docetaxel and post-abiraterone patient population. Crown Copyright (C) 2013 Published by Elsevier Ltd. All rights reserved.
引用
收藏
页码:78 / 84
页数:7
相关论文
共 14 条
[1]
[Anonymous], ASCO M S
[2]
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
[3]
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
[4]
New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1) [J].
Eisenhauer, E. A. ;
Therasse, P. ;
Bogaerts, J. ;
Schwartz, L. H. ;
Sargent, D. ;
Ford, R. ;
Dancey, J. ;
Arbuck, S. ;
Gwyther, S. ;
Mooney, M. ;
Rubinstein, L. ;
Shankar, L. ;
Dodd, L. ;
Kaplan, R. ;
Lacombe, D. ;
Verweij, J. .
EUROPEAN JOURNAL OF CANCER, 2009, 45 (02) :228-247
[5]
Molecular Pathways: Inhibiting Steroid Biosynthesis in Prostate Cancer [J].
Ferraldeschi, Roberta ;
Sharifi, Nima ;
Auchus, Richard J. ;
Attard, Gerhardt .
CLINICAL CANCER RESEARCH, 2013, 19 (13) :3353-3359
[6]
Androgen Receptor Splice Variants Mediate Enzalutamide Resistance in Castration-Resistant Prostate Cancer Cell Lines [J].
Li, Yingming ;
Chan, Siu Chiu ;
Brand, Lucas J. ;
Hwang, Tae Hyun ;
Silverstein, Kevin A. T. ;
Dehm, Scott M. .
CANCER RESEARCH, 2013, 73 (02) :483-489
[7]
Antitumour activity of abiraterone acetate against metastatic castration-resistant prostate cancer progressing after docetaxel and enzalutamide (MDV3100) [J].
Loriot, Y. ;
Bianchini, D. ;
Ileana, E. ;
Sandhu, S. ;
Patrikidou, A. ;
Pezaro, C. ;
Albiges, L. ;
Attard, G. ;
Fizazi, K. ;
De Bono, J. S. ;
Massard, C. .
ANNALS OF ONCOLOGY, 2013, 24 (07) :1807-1812
[8]
McCaffery M., 1993, PAIN CLIN MANUAL NUR
[9]
Clinical activity of abiraterone acetate in patients with metastatic castration-resistant prostate cancer progressing after enzalutamide [J].
Noonan, K. L. ;
North, S. ;
Bitting, R. L. ;
Armstrong, A. J. ;
Ellard, S. L. ;
Chi, K. N. .
ANNALS OF ONCOLOGY, 2013, 24 (07) :1802-1807
[10]
Interactions of Abiraterone, Eplerenone, and Prednisolone with Wild-type and Mutant Androgen Receptor: A Rationale for Increasing Abiraterone Exposure or Combining with MDV3100 [J].
Richards, Juliet ;
Lim, Ai Chiin ;
Hay, Colin W. ;
Taylor, Angela E. ;
Wingate, Anna ;
Nowakowska, Karolina ;
Pezaro, Carmel ;
Carreira, Suzanne ;
Goodall, Jane ;
Arlt, Wiebke ;
McEwan, Iain J. ;
de Bono, Johann S. ;
Attard, Gerhardt .
CANCER RESEARCH, 2012, 72 (09) :2176-2182