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Effectiveness of Deferred Combined Androgen Blockade Therapy Predicts Efficacy in Abiraterone Acetate Treated Metastatic Castration-Resistant Prostate Cancer Patients after Docetaxel

Introduction: Conventional anti-androgen regimens were widely used as an initiation or combined androgen blockade (CAB) therapy in advanced prostate cancer patients. Currently, new androgen pathway inhibitors such as abiraterone acetate (AA) and enzalutamide had been proven effective in metastatic c...

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Autores principales: Li, Jian-Ri, Chiu, Kun-Yuan, Wang, Shian-Shiang, Yang, Cheng-Kuang, Chen, Chuan-Shu, Ho, Hao-Chung, Hung, Chi-Feng, Cheng, Chen-Li, Yang, Chi-Rei, Chen, Cheng-Che, Wang, Shu-Chi, Lin, Chia-Yen, Chang, Chao-Hsiang, Hsu, Chiann-Yi, Ou, Yen-Chuan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5702804/
https://www.ncbi.nlm.nih.gov/pubmed/29213237
http://dx.doi.org/10.3389/fphar.2017.00836
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author Li, Jian-Ri
Chiu, Kun-Yuan
Wang, Shian-Shiang
Yang, Cheng-Kuang
Chen, Chuan-Shu
Ho, Hao-Chung
Hung, Chi-Feng
Cheng, Chen-Li
Yang, Chi-Rei
Chen, Cheng-Che
Wang, Shu-Chi
Lin, Chia-Yen
Chang, Chao-Hsiang
Hsu, Chiann-Yi
Ou, Yen-Chuan
author_facet Li, Jian-Ri
Chiu, Kun-Yuan
Wang, Shian-Shiang
Yang, Cheng-Kuang
Chen, Chuan-Shu
Ho, Hao-Chung
Hung, Chi-Feng
Cheng, Chen-Li
Yang, Chi-Rei
Chen, Cheng-Che
Wang, Shu-Chi
Lin, Chia-Yen
Chang, Chao-Hsiang
Hsu, Chiann-Yi
Ou, Yen-Chuan
author_sort Li, Jian-Ri
collection PubMed
description Introduction: Conventional anti-androgen regimens were widely used as an initiation or combined androgen blockade (CAB) therapy in advanced prostate cancer patients. Currently, new androgen pathway inhibitors such as abiraterone acetate (AA) and enzalutamide had been proven effective in metastatic castration resistant prostate cancer. In this study, we attempt to analyze the role of conventional anti-androgen drugs as deferred CAB therapy in castration-resistant prostate cancer patients. Materials and Methods: From 2012 to 2017, 48 metastatic castration-resistant prostate cancer (CRPC) patients who received sequential treatments with primary androgen blockade, oral anti-androgen regimens, and docetaxel followed by AA treatment were included. We defined effective deferred CAB as any decline of PSA after add-on antiandrogen after CRPC. Patients were separated into effective and ineffective deferred CAB. Comparison between two groups in the first line androgen deprivation therapy duration, CRPC PSA level, pre-AA PSA level, chemotherapy dosages, duration, and patients progression free survival and overall survival after AA treatment were analyzed. Results: Twenty-three patients (47.9%) achieved PSA decline after deferred CAB. Among total 48 patients, 24 patients experienced PSA decline more than 50% after AA treatment. The median PSA progression-free survival and overall survival after AA treatment in the total cohort of 48 patients were 4.4 and 24.3 months, respectively. The effective deferred CAB group showed significantly lower PSA level, lower percentage of PSA progression, higher total follow-up duration, higher percentage of surviving patients, better progression free survival, and overall survival estimate after AA treatment. Of the eight variables analyzed, effectiveness in deferred CAB showed positive association to progression free survival (HR 0.29, 95% CI 0.12–0.67, p = 0.004) and overall survival (HR 0.24, 95% CI 0.07–0.81, p = 0.022). First line androgen deprivation therapy (ADT) duration also showed positive association to overall survival (HR 0.95, 95% CI 0.91–0.99, p = 0.023). Conclusions: Effectiveness of deferred CAB therapy was positively associated with progression free survival and overall survival of AA treatment after docetaxel. It can be used as a pre-treatment predictor.
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spelling pubmed-57028042017-12-06 Effectiveness of Deferred Combined Androgen Blockade Therapy Predicts Efficacy in Abiraterone Acetate Treated Metastatic Castration-Resistant Prostate Cancer Patients after Docetaxel Li, Jian-Ri Chiu, Kun-Yuan Wang, Shian-Shiang Yang, Cheng-Kuang Chen, Chuan-Shu Ho, Hao-Chung Hung, Chi-Feng Cheng, Chen-Li Yang, Chi-Rei Chen, Cheng-Che Wang, Shu-Chi Lin, Chia-Yen Chang, Chao-Hsiang Hsu, Chiann-Yi Ou, Yen-Chuan Front Pharmacol Pharmacology Introduction: Conventional anti-androgen regimens were widely used as an initiation or combined androgen blockade (CAB) therapy in advanced prostate cancer patients. Currently, new androgen pathway inhibitors such as abiraterone acetate (AA) and enzalutamide had been proven effective in metastatic castration resistant prostate cancer. In this study, we attempt to analyze the role of conventional anti-androgen drugs as deferred CAB therapy in castration-resistant prostate cancer patients. Materials and Methods: From 2012 to 2017, 48 metastatic castration-resistant prostate cancer (CRPC) patients who received sequential treatments with primary androgen blockade, oral anti-androgen regimens, and docetaxel followed by AA treatment were included. We defined effective deferred CAB as any decline of PSA after add-on antiandrogen after CRPC. Patients were separated into effective and ineffective deferred CAB. Comparison between two groups in the first line androgen deprivation therapy duration, CRPC PSA level, pre-AA PSA level, chemotherapy dosages, duration, and patients progression free survival and overall survival after AA treatment were analyzed. Results: Twenty-three patients (47.9%) achieved PSA decline after deferred CAB. Among total 48 patients, 24 patients experienced PSA decline more than 50% after AA treatment. The median PSA progression-free survival and overall survival after AA treatment in the total cohort of 48 patients were 4.4 and 24.3 months, respectively. The effective deferred CAB group showed significantly lower PSA level, lower percentage of PSA progression, higher total follow-up duration, higher percentage of surviving patients, better progression free survival, and overall survival estimate after AA treatment. Of the eight variables analyzed, effectiveness in deferred CAB showed positive association to progression free survival (HR 0.29, 95% CI 0.12–0.67, p = 0.004) and overall survival (HR 0.24, 95% CI 0.07–0.81, p = 0.022). First line androgen deprivation therapy (ADT) duration also showed positive association to overall survival (HR 0.95, 95% CI 0.91–0.99, p = 0.023). Conclusions: Effectiveness of deferred CAB therapy was positively associated with progression free survival and overall survival of AA treatment after docetaxel. It can be used as a pre-treatment predictor. Frontiers Media S.A. 2017-11-22 /pmc/articles/PMC5702804/ /pubmed/29213237 http://dx.doi.org/10.3389/fphar.2017.00836 Text en Copyright © 2017 Li, Chiu, Wang, Yang, Chen, Ho, Hung, Cheng, Yang, Chen, Wang, Lin, Chang, Hsu and Ou. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Li, Jian-Ri
Chiu, Kun-Yuan
Wang, Shian-Shiang
Yang, Cheng-Kuang
Chen, Chuan-Shu
Ho, Hao-Chung
Hung, Chi-Feng
Cheng, Chen-Li
Yang, Chi-Rei
Chen, Cheng-Che
Wang, Shu-Chi
Lin, Chia-Yen
Chang, Chao-Hsiang
Hsu, Chiann-Yi
Ou, Yen-Chuan
Effectiveness of Deferred Combined Androgen Blockade Therapy Predicts Efficacy in Abiraterone Acetate Treated Metastatic Castration-Resistant Prostate Cancer Patients after Docetaxel
title Effectiveness of Deferred Combined Androgen Blockade Therapy Predicts Efficacy in Abiraterone Acetate Treated Metastatic Castration-Resistant Prostate Cancer Patients after Docetaxel
title_full Effectiveness of Deferred Combined Androgen Blockade Therapy Predicts Efficacy in Abiraterone Acetate Treated Metastatic Castration-Resistant Prostate Cancer Patients after Docetaxel
title_fullStr Effectiveness of Deferred Combined Androgen Blockade Therapy Predicts Efficacy in Abiraterone Acetate Treated Metastatic Castration-Resistant Prostate Cancer Patients after Docetaxel
title_full_unstemmed Effectiveness of Deferred Combined Androgen Blockade Therapy Predicts Efficacy in Abiraterone Acetate Treated Metastatic Castration-Resistant Prostate Cancer Patients after Docetaxel
title_short Effectiveness of Deferred Combined Androgen Blockade Therapy Predicts Efficacy in Abiraterone Acetate Treated Metastatic Castration-Resistant Prostate Cancer Patients after Docetaxel
title_sort effectiveness of deferred combined androgen blockade therapy predicts efficacy in abiraterone acetate treated metastatic castration-resistant prostate cancer patients after docetaxel
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5702804/
https://www.ncbi.nlm.nih.gov/pubmed/29213237
http://dx.doi.org/10.3389/fphar.2017.00836
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