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abiraterone response time in mCRPC

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https://www.readbyqxmd.com/read/27763885/duration-of-response-to-first-androgen-deprivation-therapy-time-to-castration-resistance-prostate-cancer-and-outcome-of-metastatic-castration-resistance-prostate-cancer-patients-treated-with-abiraterone-acetate
#1
Silvana Giacinti, Paolo Carlini, Michela Roberto, Maria Bassanelli, Lidia Strigari, Francesco Pavese, Anna M Aschelter, Alessandra Felici, Maurizio Valeriani, Francesco Cognetti, Paolo Marchetti
Abiraterone acetate (AA) demonstrated its efficacy in the treatment of patients with metastatic castration resistance prostate cancer (mCRPC) in predocetaxel and postdocetaxel setting. However, we learn from pivotal studies that forms of primary and acquired resistance to this drug exist. Patient selection becomes so crucial to optimize treatment results. Potential predictive biomarkers have been identified but are not yet validated. In this scenario, clinical features and disease characteristics may still be of value in selecting patients for different treatments...
January 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/27544669/enzalutamide-as-a-fourth-or-fifth-line-treatment-option-for-metastatic-castration-resistant-prostate-cancer
#2
Sushil K Badrising, Vincent van der Noort, Paul Hamberg, Jules L L M Coenen, Maureen J Aarts, Inge M van Oort, Alfons J M van den Eertwegh, Maartje Los, H Pieter van den Berg, Hans Gelderblom, Suzan Vrijaldenhoven, Emile D Kerver, Theo van Voorthuizen, Igle J de Jong, John B Haanen, Andries M Bergman
OBJECTIVE: To evaluate the efficacy of enzalutamide (Enz) as fourth- or fifth-line treatment in men with metastasized castration-resistant prostate cancer (mCRPC), by analyzing a retrospective cohort of heavily pretreated patients. METHODS: We evaluated toxicity, overall survival (OS), progression-free survival (PFS) and time to prostate-specific antigen (PSA) progression data from 47 CRPC patients treated with fourth- or fifth-line Enz. RESULTS: All patients were treated with docetaxel and abiraterone acetate and 42 patients (89%) with cabazitaxel...
August 20, 2016: Oncology
https://www.readbyqxmd.com/read/27527643/comparing-sequencing-of-abiraterone-and-enzalutamide-in-men-with-metastatic-castration-resistant-prostate-cancer-a-retrospective-study
#3
Benjamin L Maughan, Brandon Luber, Rosa Nadal, Emmanuel S Antonarakis
BACKGROUND: There are no validated clinical decision tools to aid optimal treatment selection in men with metastatic castration-resistant prostate cancer (mCRPC). Frequently, abiraterone and enzalutamide are used prior to chemotherapy in mCRPC, given the more favorable safety profiles. However, there is no published data on clinical outcomes regarding best sequencing of these two agents. METHODS: A retrospective analysis of consecutive mCRPC patients treated with enzalutamide and abiraterone at Johns Hopkins was conducted...
August 16, 2016: Prostate
https://www.readbyqxmd.com/read/27504016/in-vitro-and-in-vivo-drug-drug-interaction-studies-to-assess-the-effect-of-abiraterone-acetate-abiraterone-and-metabolites-of-abiraterone-on-cyp2c8-activity
#4
Johan Monbaliu, Martha Gonzalez, Apexa Bernard, James Jiao, Carlo Sensenhauser, Jan Snoeys, Hans Stieltjes, Inneke Wynant, Johan W Smit, Caly Chien
Abiraterone acetate, the prodrug of the cytochrome P450 C17 inhibitor abiraterone, plus prednisone is approved for treatment of metastatic castration-resistant prostate cancer. We explored whether abiraterone interacts with drugs metabolized by CYP2C8, an enzyme responsible for the metabolism of many drugs. Abiraterone acetate and abiraterone and its major metabolites, abiraterone sulfate and abiraterone sulfate N-oxide, inhibited CYP2C8 in human liver microsomes, with IC50 values near or below the peak total concentrations observed in patients with metastatic castration-resistant prostate cancer (IC50 values: 1...
October 2016: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/27450512/enzalutamide-in-patients-with-castration-resistant-prostate-cancer-progressing-after-docetaxel-retrospective-analysis-of-the-swiss-enzalutamide-named-patient-program
#5
Dimitrios Papazoglou, Luciano Wannesson, Dominik Berthold, Richard Cathomas, Silke Gillessen, Christian Rothermundt, Loretta Hasler, Ralph Winterhalder, Andreas Barth, Walter Mingrone, Catrina Uhlmann Nussbaum, Lukas von Rohr, Philippe von Burg, Mathias Schmid, Jürg Richner, Sylvia Baumann, Reto Kühne, Frank Stenner, Sacha I Rothschild
BACKGROUND: Enzalutamide is a second-generation androgen receptor (AR) inhibitor that binds to and blocks the AR with higher affinity than previously available AR inhibitors. High activity has been proven in patients with metastatic castration-resistant prostate cancer (mCRPC) previously treated with docetaxel and in chemotherapy-naive patients with mCRPC. However, its activity in patients previously treated with other novel agents (for example, abiraterone and/or cabazitaxel), remains controversial...
June 23, 2016: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/27436429/ar-v7-transcripts-in-whole-blood-rna-of-patients-with-metastatic-castration-resistant-prostate-cancer-correlate-with-response-to-abiraterone-acetate
#6
Tilman Todenhöfer, Arun Azad, Craig Stewart, Jian Gao, Bernhard J Eigl, Martin E Gleave, Anthony M Joshua, Peter C Black, Kim N Chi
PURPOSE: The expression of AR-V7 (androgen receptor splice variant) 7 in circulating tumor cells has been associated with resistance to abiraterone and enzalutamide in patients with metastatic castration resistant prostate cancer. We used a sensitive, whole blood reverse transcriptase-polymerase chain reaction assay that does not require circulating tumor cell enrichment to correlate outcomes of abiraterone with whole blood expression of AR-V7 and other prostate cancer associated transcripts...
July 17, 2016: Journal of Urology
https://www.readbyqxmd.com/read/27409606/common-genetic-variation-in-cyp17a1-and-response-to-abiraterone-acetate-in-patients-with-metastatic-castration-resistant-prostate-cancer
#7
Moritz Binder, Ben Y Zhang, David W Hillman, Rhea Kohli, Tanvi Kohli, Adam Lee, Manish Kohli
Treatment with abiraterone acetate and prednisone (AA/P) prolongs survival in metastatic castration-resistant prostate cancer (mCRPC) patients. We evaluated the genetic variation in CYP17A1 as predictive of response to AA/P. A prospective collection of germline DNA prior to AA/P initiation and follow-up of a mCRPC cohort was performed. Five common single-nucleotide polymorphisms (SNPs) in CYP17A1 identified using a haplotype-based tagging algorithm were genotyped. Clinical outcomes included biochemical response and time to biochemical progression on AA/P...
2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27278777/association-of-early-psa-decline-and-time-to-psa-progression-in-abiraterone-acetate-treated-metastatic-castration-resistant-prostate-cancer-a-post-hoc-analysis-of-japanese-phase-2-trials
#8
Masahiko Nakayama, Hisanori Kobayashi, Tomihiro Takahara, Ryo Oyama, Keiichiro Imanaka, Kazutake Yoshizawa
BACKGROUND: Previous studies have demonstrated an association between prostate-specific antigen (PSA) kinetics and predictive value for treatment outcomes. Abiraterone acetate (AA) is a newly approved cytochrome-P450C17 inhibitor for treatment of metastatic castration-resistant prostate cancer (mCRPC), and few studies have evaluated PSA kinetics using AA so far. Results of a study evaluating PSA kinetics in the beginning of AA and enzalutamide responded chemotherapy-treated patients suggested different trends between the drugs...
2016: BMC Urology
https://www.readbyqxmd.com/read/27212123/indirect-comparison-between-abiraterone-acetate-and-enzalutamide-for-the-treatment-of-metastatic-castration-resistant-prostate-cancer-a-systematic-review
#9
Wei Zhang, Teng-Yun Wu, Qi Chen, Xiao-Lei Shi, Guang-An Xiao, Lin Zhao, Chuan-Liang Xu, Tie Zhou, Ying-Hao Sun
This study was designed to evaluate the efficacy, tolerability, and sequential administration of abiraterone acetate (AA) and enzalutamide (Enz) for metastatic castration-resistant prostate cancer (mCRPC). A literature search was performed with PubMed, Embase, and Web of Science databases to identify relevant studies. Reviewed literature included published phase III trials of AA or Enz in mCRPC and studies regarding their sequential administration. Given the difference in control arms in AA (active comparator) and Enz (true placebo) randomized phase III studies, indirect comparisons between AA and Enz in mCRPC showed no statistically significant difference in overall survival in prechemotherapy and postchemotherapy settings (HR: 0...
May 20, 2016: Asian Journal of Andrology
https://www.readbyqxmd.com/read/27150425/inherited-variants-in-sult1e1-and-response-to-abiraterone-acetate-by-men-with-metastatic-castration-refractory-prostate-cancer
#10
Neeraj Agarwal, Anitha B Alex, James M Farnham, Shiven Patel, David Gill, Tyler H Buckley, Robert A Stephenson, Lisa Cannon-Albright
PURPOSE: Germline variations in genes involved in androgen biosynthesis and metabolic pathways may predict the response to abiraterone acetate in men with metastatic, castration refractory prostate cancer. The variations may serve as prognostic and predictive biomarkers to allow for more individualized therapy. MATERIALS AND METHODS: We evaluated 832 single nucleotide polymorphisms from the OmniExpress genotyping platform (Illumina®) in the boundaries of 61 candidate genes reported to be involved in the androgen metabolic pathway...
October 2016: Journal of Urology
https://www.readbyqxmd.com/read/27148695/genomic-alterations-in-cell-free-dna-and-enzalutamide-resistance-in-castration-resistant-prostate-cancer
#11
Alexander W Wyatt, Arun A Azad, Stanislav V Volik, Matti Annala, Kevin Beja, Brian McConeghy, Anne Haegert, Evan W Warner, Fan Mo, Sonal Brahmbhatt, Robert Shukin, Stephane Le Bihan, Martin E Gleave, Matti Nykter, Colin C Collins, Kim N Chi
Importance: The molecular landscape underpinning response to the androgen receptor (AR) antagonist enzalutamide in patients with metastatic castration-resistant prostate cancer (mCRPC) is undefined. Consequently, there is an urgent need for practical biomarkers to guide therapy selection and elucidate resistance. Although tissue biopsies are impractical to perform routinely in the majority of patients with mCRPC, the analysis of plasma cell-free DNA (cfDNA) has recently emerged as a minimally invasive method to explore tumor characteristics...
May 5, 2016: JAMA Oncology
https://www.readbyqxmd.com/read/27015255/budget-impact-of-enzalutamide-for-chemotherapy-na%C3%A3-ve-metastatic-castration-resistant-prostate-cancer
#12
Cat N Bui, Ken O'Day, Scott Flanders, Nina Oestreicher, Peter Francis, Linda Posta, Breanna Popelar, Hong Tang, Mark Balk
BACKGROUND: Prostate cancer is expected to account for approximately one quarter of all new diagnoses of cancer in American men in 2015. The cost of prostate cancer care is expected to reach $15.1 billion by the year 2020, up from $11.9 billion in 2010. Given the high burden of prostate cancer, health care payers are interested in quantifying the potential budget impact of new therapies. OBJECTIVE: To estimate the budget impact of enzalutamide for the treatment of chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC) from a U...
February 2016: Journal of Managed Care & Specialty Pharmacy
https://www.readbyqxmd.com/read/27001043/abiraterone-acetate-in-metastatic-castration-resistant-prostate-cancer-the-unanticipated-real-world-clinical-experience
#13
Darren M C Poon, Kuen Chan, S H Lee, T W Chan, Henry Sze, Eric K C Lee, Daisy Lam, Michelle F T Chan
BACKGROUND: There is much interest in confirming whether the efficacy of abiraterone acetate (AA) demonstrated within the trial setting is reproducible in routine clinical practice. We report the clinical outcome of metastatic castration-resistant prostate cancer (mCRPC) patients treated with AA in real-life clinical practice. METHODS: The clinical records of mCRPC patients treated with AA from all 6 public oncology centers in Hong Kong between August 2011 and December 2014 were reviewed...
2016: BMC Urology
https://www.readbyqxmd.com/read/26971191/a-single-center-experience-with-abiraterone-as-treatment-for-metastatic-castration-resistant-prostate-cancer
#14
Anita Thortzen, Stine Thim, Martin Andreas Røder, Klaus Brasso
BACKGROUND: Continuous stimulation of the androgen receptor (AR) axis is a prerequisite for growth in castration-resistant prostate cancer (CRPC). Abiraterone acetate (AA) is a potent inhibitor of extracellular and intracellular androgen synthesis by inhibition of the CYP-17 enzyme system, which has been shown to be up-regulated in CRPC. AA was recently introduced in the management of patients with metastatic CRPC (mCRPC) both before and after taxane-based chemotherapy. The purpose of this study is to report the initial clinical experience obtained from mCRPC patients managed on AA at Rigshospitalet, Denmark, and compare the results with phase III trial outcomes...
July 2016: Urologic Oncology
https://www.readbyqxmd.com/read/26965561/prostate-specific-antigen-decline-after-4-weeks-of-treatment-with-abiraterone-acetate-and-overall-survival-in-patients-with-metastatic-castration-resistant-prostate-cancer
#15
Pasquale Rescigno, David Lorente, Diletta Bianchini, Roberta Ferraldeschi, Michael P Kolinsky, Spyridon Sideris, Zafeiris Zafeiriou, Semini Sumanasuriya, Alan D Smith, Niven Mehra, Anuradha Jayaram, Raquel Perez-Lopez, Joaquin Mateo, Chris Parker, David P Dearnaley, Nina Tunariu, Alison Reid, Gerhardt Attard, Johann S de Bono
BACKGROUND: The availability of multiple new treatments for metastatic castration-resistant prostate cancer (mCRPC) mandates earlier treatment switches in the absence of a response. A decline in prostate-specific antigen (PSA) is widely used to monitor treatment response, but is not validated as an intermediate endpoint for overall survival (OS). OBJECTIVE: To evaluate the association between early PSA decline and OS following abiraterone acetate (AA) treatment...
March 7, 2016: European Urology
https://www.readbyqxmd.com/read/26857146/the-influence-of-prednisone-on-the-efficacy-of-docetaxel-in-men-with-metastatic-castration-resistant-prostate-cancer
#16
B A Teply, B Luber, S R Denmeade, E S Antonarakis
BACKGROUND: Prednisone and other corticosteroids can provide palliation and tumor responses in patients with prostate cancer. The combination of docetaxel and prednisone was the first treatment shown to prolong survival in men with metastatic castration-resistant prostate cancer (mCRPC). Since the approval of docetaxel in 2004, additional treatments are available, including abiraterone, which is also administered with prednisone. Therefore, patients are increasingly likely to have prednisone therapy several times throughout their disease course, and the contribution of prednisone to the efficacy of docetaxel is unknown...
March 2016: Prostate Cancer and Prostatic Diseases
https://www.readbyqxmd.com/read/26850781/abiraterone-acetate-post-docetaxel-for-metastatic-castration-resistant-prostate-cancer-in-the-belgian-compassionate-use-program
#17
Charles Van Praet, Sylvie Rottey, Fransien Van Hende, Gino Pelgrims, Wim Demey, Filip Van Aelst, Wim Wynendaele, Thierry Gil, Peter Schatteman, Bertrand Filleul, Dennis Schallier, Jean-Pascal Machiels, Dirk Schrijvers, Els Everaert, Lionel D'Hondt, Patrick Werbrouck, Joanna Vermeij, Jeroen Mebis, Marylene Clausse, Marika Rasschaert, Joanna Van Erps, Jolanda Verheezen, Jan Van Haverbeke, Jean-Charles Goeminne, Nicolaas Lumen
BACKGROUND: Abiraterone acetate (AA) is licensed for treating metastatic castration-resistant prostate cancer (mCRPC). Real-world data on oncological outcome after AA are scarce. The current study assesses efficacy and safety of AA in mCRPC patients previously treated with docetaxel who started treatment during the Belgian compassionate use program (January 2011-July 2012). PATIENTS AND METHODS: Records from 368 patients with mCRPC from 23 different Belgian hospitals who started AA 1000mg per day with 10mg prednisone or equivalent were retrospectively reviewed (September 2013-December 2014)...
June 2016: Urologic Oncology
https://www.readbyqxmd.com/read/26609008/does-gleason-score-at-initial-diagnosis-predict-efficacy-of-abiraterone-acetate-therapy-in-patients-with-metastatic-castration-resistant-prostate-cancer-an-analysis-of-abiraterone-acetate-phase-iii-trials
#18
K Fizazi, T W Flaig, M Stöckle, H I Scher, J S de Bono, D E Rathkopf, C J Ryan, T Kheoh, J Li, M B Todd, T W Griffin, A Molina, C H Ohlmann
BACKGROUND: The usefulness of Gleason score (<8 or ≥8) at initial diagnosis as a predictive marker of response to abiraterone acetate (AA) plus prednisone in patients with metastatic castration-resistant prostate cancer (mCRPC) was explored retrospectively. PATIENTS AND METHODS: Initial diagnosis Gleason score was obtained in 1048 of 1195 (COU-AA-301, post-docetaxel) and 996 of 1088 (COU-AA-302, chemotherapy-naïve) patients treated with AA 1 g plus prednisone 5 mg twice daily by mouth or placebo plus prednisone...
April 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/26508309/prior-endocrine-therapy-impact-on-abiraterone-acetate-clinical-efficacy-in-metastatic-castration-resistant-prostate-cancer-post-hoc-analysis-of-randomised-phase-3-studies
#19
Joaquim Bellmunt, Thian Kheoh, Margaret K Yu, Matthew R Smith, Eric J Small, Peter F A Mulders, Karim Fizazi, Dana E Rathkopf, Fred Saad, Howard I Scher, Mary-Ellen Taplin, Ian D Davis, Dirk Schrijvers, Andrew Protheroe, Arturo Molina, Peter De Porre, Thomas W Griffin, Johann S de Bono, Charles J Ryan, Stéphane Oudard
BACKGROUND: The duration of prior hormonal treatment can predict responses to subsequent therapy in patients with metastatic castration-resistant prostate cancer (mCRPC). OBJECTIVE: To determine if prior endocrine therapy duration is an indicator of abiraterone acetate (AA) sensitivity. DESIGN, SETTING, AND PARTICIPANTS: Post-hoc exploratory analysis of randomised phase 3 studies examining post-docetaxel (COU-AA-301) or chemotherapy-naïve mCRPC (COU-AA-302) patients receiving AA...
May 2016: European Urology
https://www.readbyqxmd.com/read/26437324/docetaxel-rechallenge-in-metastatic-castration-resistant-prostate-cancer-any-place-in-the-modern-treatment-scenario-an-intention-to-treat-evaluation
#20
Sergio Bracarda, Claudia Caserta, Luca Galli, Paolo Carlini, Ilaria Pastina, Michele Sisani, Simona Scali, Alketa Hamzaj, Lisa Derosa, Alessandra Felici, Marta Rossi, Amelia Altavilla, Aldo Chioni, Verena De Angelis
BACKGROUND: We evaluated the possible advantages of a docetaxel (DCT) rechallenge strategy in metastatic castration-resistant prostate cancer (mCRPC) patients, also given the possible earlier positioning of this treatment option in the modern scenario. PATIENTS & METHODS: All mCRPC patients planned for DCT chemotherapy rechallenge in our institutions were evaluated. RESULTS: Of 128 patients, 98 achieved disease control on the initial DCT round...
November 2015: Future Oncology
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