Systematic Reviews
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Oncol. Aug 10, 2015; 6(4): 64-72
Published online Aug 10, 2015. doi: 10.5306/wjco.v6.i4.64
Comparative analysis of the effectiveness of abiraterone before and after docetaxel in patients with metastatic castration-resistant prostate cancer
Raji Shameem, Muhammad Saad Hamid, Kevin Y Xu, Shenhong Wu
Raji Shameem, Department of Hematology/Oncology, Fox Chase Cancer Center, Philadelphia, PA 19111, United States
Muhammad Saad Hamid, Department of Internal Medicine, Detroit Medical Center/Wayne State University, Detroit, MI 48201, United States
Kevin Y Xu, Department of Medical Education, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States
Shenhong Wu, Division of Hematology/Oncology, Department of Medicine, Stony Brook University School of Medicine, Stony Brook, NY 11794, United States
Shenhong Wu, Northport VA Medical Center, Northport, NY 11768, United States
Author contributions: Wu S designed research; Shameem R and Wu S performed research; Wu S contributed new reagents or analytic tools; Shameem R and Wu S analyzed data; Shameem R, Hamid MS and Xu KY wrote the paper.
Conflict-of-interest statement: Dr. Wu is a speaker for Pfizer and Novartis. No financial support was provided for this study. All remaining authors have declared no conflicts of interests.
Data sharing statement: Technical appendix and statistical code available from the corresponding author
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Correspondence to: Shenhong Wu, MD, PhD, Associate Professor, Division of Hematology/Oncology, Department of Medicine, Stony Brook University School of Medicine, Stony Brook, NY 11794, United States.
Telephone: +1-631-6381000 Fax: +1-631-6380915
Received: October 26, 2014
Peer-review started: October 28, 2014
First decision: December 26, 2014
Revised: May 18, 2015
Accepted: June 4, 2015
Article in press: June 8, 2015
Published online: August 10, 2015

AIM: To study the efficacy and safety of abiraterone in patients with and without prior chemotherapy.

METHODS: The databases including PubMed and abstracts presented at the American Society of Clinical Oncology meetings up to April 2014 were systematically searched. Eligible studies included randomized controlled trials (RCTs) in which abiraterone plus prednisone was compared to placebo plus prednisone in metastatic castration-resistant prostate cancer (CRPC) patients. The summary incidence, relative risk, hazard ratio and 95%CI were calculated using random or fixed-effects models. Heterogeneity test was performed to test between-study differences in efficacy and toxicity.

RESULTS: A total of two phase III RCTs were included in our analysis, with metastatic CPRC patients before (n = 1088) and after chemotherapy (n = 1195). Prior chemotherapy did not significantly alter the effect of abiraterone on overall survival (P = 0.92) and prostate-specific antigen (PSA) progression-free survival (P = 0.13), but reduced its effect on radiographic-progression-free survival (P = 0.04), objective response rate (P < 0.001), and PSA response rate (P < 0.001). Prior chemotherapy significantly increased the specific risk of fluid retention and edema (P < 0.001) and hypokalemia (P < 0.001), but decreased the risk of all-grade hypertension (P < 0.001) attributable to abiraterone. There was no significant difference of cardiac disorders associated with abiraterone between the two settings (P = 0.58).

CONCLUSION: Prior chemotherapy may reduce the effectiveness of abiraterone in patients with metastatic CRPC.

Keywords: Abiraterone, Docetaxel, Metastatic castration-resistant prostate cancer, Chemotherapy-naïve, Pre-chemotherapy, Post-chemotherapy

Core tip: Our meta-analysis has demonstrated that pre-chemotherapy may affect the efficacy and toxicity of abiraterone treatment in patients with metastatic castration-resistant prostate cancer. Abiraterone was associated with significantly increased radiographic-progression-free survival, objective response rate, and prostate-specific antigen response rate in the pre-chemotherapy setting when compared to the post-chemotherapy setting. In addition, abiraterone in the pre-chemotherapy setting had a significant lower risk of all-grade fluid retention and edema (P < 0.001), and hypokalemia (P < 0.001), but had a higher risk of all-grade hypertension (P < 0.001) when compared to post-chemotherapy.