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Abiraterone response time

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https://www.readbyqxmd.com/read/28314611/clinical-outcomes-from-androgen-signaling-directed-therapy-after-treatment-with-abiraterone-acetate-and-prednisone-in-patients-with-metastatic-castration-resistant-prostate-cancer-post-hoc-analysis-of-cou-aa-302
#1
Matthew R Smith, Fred Saad, Dana E Rathkopf, Peter F A Mulders, Johann S de Bono, Eric J Small, Neal D Shore, Karim Fizazi, Thian Kheoh, Jinhui Li, Peter De Porre, Mary B Todd, Margaret K Yu, Charles J Ryan
In the COU-AA-302 trial, abiraterone acetate plus prednisone significantly increased overall survival for patients with chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC). Limited information exists regarding response to subsequent androgen signaling-directed therapies following abiraterone acetate plus prednisone in patients with mCRPC. We investigated clinical outcomes associated with subsequent abiraterone acetate plus prednisone (55 patients) and enzalutamide (33 patients) in a post hoc analysis of COU-AA-302...
March 14, 2017: European Urology
https://www.readbyqxmd.com/read/28282611/phase-ib-dose-finding-study-of-abiraterone-acetate-plus-buparlisib-bkm120-or-dactolisib-bez235-in-patients-with-castration-resistant-prostate-cancer
#2
Christophe Massard, Kim Nguyen Chi, Daniel Castellano, Johann de Bono, Gwenaelle Gravis, Luc Dirix, Jean-Pascal Machiels, Alain Mita, Begona Mellado Gonzalez, Sabine Turri, Joan Maier, Denes Csonka, Arunava Chakravartty, Karim Fizazi
BACKGROUND: The phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) signalling axis and androgen receptor (AR) pathways exhibit reciprocal feedback regulation in phosphatase and tensin homologue (PTEN)-deficient metastatic castration-resistant prostate cancer (CRPC) in preclinical models. This phase Ib study evaluated the pan-PI3K inhibitor buparlisib (BKM120) and the dual pan-PI3K/ mammalian target of rapamycin (mTOR) inhibitor dactolisib (BEZ235) in combination with abiraterone acetate (AA) in patients with CRPC...
March 3, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28213364/safety-and-antitumor-activity-of-apalutamide-arn-509-in-metastatic-castration-resistant-prostate-cancer-with-and-without-prior-abiraterone-acetate-and-prednisone
#3
Dana E Rathkopf, Emmanuel S Antonarakis, Neal D Shore, Ronald F Tutrone, Joshi J Alumkal, Charles J Ryan, Mansoor Saleh, Ralph J Hauke, Rajesh Bandekar, Edna Chow Maneval, Carla J de Boer, Margaret K Yu, Howard I Scher
PURPOSE: To evaluate the efficacy of apalutamide before or after treatment with abiraterone acetate and prednisone (AAP) in patients with progressive metastatic castration-resistant prostate cancer (mCRPC). EXPERIMENTAL DESIGN: Two cohorts were studied: AAP-naïve and post-AAP patients who had received ≥6 months of AAP. Patients had progressive mCRPC per rising prostate-specific antigen (PSA) and/or imaging, without prior chemotherapy exposure. All received apalutamide 240 mg/day...
February 17, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28188090/independent-association-between-time-to-prostate-specific-antigen-psa-nadir-and-psa-progression-free-survival-in-patients-with-docetaxel-na%C3%A3-ve-metastatic-castration-resistant-prostate-cancer-receiving-abiraterone-acetate-but-not-enzalutamide
#4
Hideaki Miyake, Takuto Hara, Keita Tamura, Takayuki Sugiyama, Hiroshi Furuse, Seiichiro Ozono, Masato Fujisawa
PURPOSE: The objective of this study was to compare the prognostic effect of time to prostate-specific antigen (PSA) nadir (TTPN) after treatment with abiraterone acetate (AA) and enzalutamide (Enz) in patients with docetaxel-naïve, metastatic castration-resistant prostate cancer (mCRPC). METHODS: This study included a total of 297 consecutive patients with mCRPC, of whom 125 and 172 received AA and Enz, respectively, without previous treatment with docetaxel and subsequently achieved any degree of PSA reduction after the administration of either agent...
February 7, 2017: Urologic Oncology
https://www.readbyqxmd.com/read/28126272/prostate-specific-antigen-response-in-black-and-white-patients-treated-with-abiraterone-acetate-for-metastatic-castrate-resistant-prostate-cancer
#5
Sundhar Ramalingam, Michael S Humeniuk, Rachel Hu, Julia Rasmussen, Patrick Healy, Yuan Wu, Michael R Harrison, Andrew J Armstrong, Daniel J George, Tian Zhang
PURPOSE: Evidence suggests differences in androgen receptor AR signaling between black (B) and white (W) patients with prostate cancer, but pivotal trials of abiraterone acetate (AA) for patients with metastatic castration-resistant prostate cancer (mCRPC) enrolled few black patients, a population with a higher mortality from prostate cancer. Our primary objective was to determine differences in response to AA between B and W patients. METHODS: We performed a retrospective case-control study of B vs...
January 23, 2017: Urologic Oncology
https://www.readbyqxmd.com/read/28101887/abiraterone-or-enzalutamide-in-advanced-castration-resistant-prostate-cancer-an-indirect-comparison
#6
Akhil Chopra, Mina Georgieva, Gilberto Lopes, Chong Ming Yeo, Benjamin Haaland
BACKGROUND: To perform a comparative effectiveness analyses between enzalutamide and abiraterone acetate in both the pre-docetaxel and post-docetaxel settings based on published phase III randomized trials. METHODS: The primary measure of efficacy was the posterior probability that enzalutamide outperforms abiraterone acetate (AA) with prednisone in terms of overall survival (OS) on average. Indirect meta-estimates were generated from four randomized studies in the context of a Bayesian hierarchical model with study-specific efficacy estimates meta-analyzed on the log scale...
May 2017: Prostate
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
#7
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
#8
MULTICENTER STUDY
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...
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
#9
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...
January 2017: 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
#10
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
#11
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
#12
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...
January 2017: 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
#13
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...
July 9, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27289566/decline-in-circulating-tumor-cell-count-and-treatment-outcome-in-advanced-prostate-cancer
#14
David Lorente, David Olmos, Joaquin Mateo, Diletta Bianchini, George Seed, Martin Fleisher, Daniel C Danila, Penny Flohr, Mateus Crespo, Ines Figueiredo, Susana Miranda, Kurt Baeten, Arturo Molina, Thian Kheoh, Robert McCormack, Leon W M M Terstappen, Howard I Scher, Johann S de Bono
BACKGROUND: Treatment response biomarkers are urgently needed for castration-resistant prostate cancer (CRPC). Baseline and post-treatment circulating tumor cell (CTC) counts of ≥5 cells/7.5ml are associated with poor CRPC outcome. OBJECTIVE: To determine the value of a ≥30% CTC decline as a treatment response indicator. DESIGN, SETTING, AND PARTICIPANTS: We identified patients with a baseline CTC count ≥5 cells/7.5ml and evaluable post-treatment CTC counts in two prospective trials...
December 2016: European Urology
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
#15
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...
June 8, 2016: BMC Urology
https://www.readbyqxmd.com/read/27255944/androgen-receptor-splice-variant-7-in-castration-resistant-prostate-cancer-clinical-considerations
#16
REVIEW
Alan H Bryce, Emmanuel S Antonarakis
Constitutively-active ligand-independent splice variants of the androgen receptor are an adaptive response by prostate cancer cells to escape androgen deprivation therapy and novel androgen receptor-directed treatments. Androgen receptor splice variant 7 is the most common splice variant detected in clinical biospecimens, and emerging data now suggest that the presence of tumoral androgen receptor splice variant 7 might be indicative of primary and acquired resistance to next-generation androgen pathway inhibitors, such as abiraterone and enzalutamide...
August 2016: International Journal of Urology: Official Journal of the Japanese Urological Association
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
#17
REVIEW
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...
March 2017: Asian Journal of Andrology
https://www.readbyqxmd.com/read/27174722/the-fluorescent-two-hybrid-assay-for-live-cell-profiling-of-androgen-receptor-modulators
#18
Jacqueline Bogner, Kourosh Zolghadr, Ian Hickson, Tina Romer, Larisa Yurlova
The androgen receptor (AR) is an important target for drug therapies combating prostate cancer. However, various acquired mutations within the AR sequence often render this receptor resistant to treatment. Ligand-induced interaction between the N- and C-termini of the AR marks the initial step in the AR signaling cascade and can thus serve as an early read-out for analysis of potential antagonists of wt and mutant AR. To measure changes of the N/C interaction in the wt and mutant AR variants upon the addition of inhibitors, we applied our recently developed Fluorescent Two-Hybrid (F2H) assay...
February 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/27157640/the-effect-of-time-to-castration-resistance-on-outcomes-with-abiraterone-and-enzalutamide-in-metastatic-prostate-cancer
#19
Jonathan Hung, Andrew R Taylor, George W Divine, Jason M Hafron, Clara Hwang
BACKGROUND: Abiraterone and enzalutamide are 2 novel androgen receptor (AR)-targeting therapies that improve survival in patients with metastatic castration-resistant prostate cancer. The factors that predict abiraterone and enzalutamide response are lacking. The objective of the present study was to determine whether the outcomes from primary androgen deprivation therapy (ADT) could predict the outcomes with subsequent novel AR-targeting therapies. MATERIALS AND METHODS: We identified 80 consecutive patients with metastatic castration-resistant prostate cancer treated with abiraterone or enzalutamide...
March 24, 2016: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/27150425/inherited-variants-in-sult1e1-and-response-to-abiraterone-acetate-by-men-with-metastatic-castration-refractory-prostate-cancer
#20
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
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