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The impact of statin use on the efficacy of abiraterone acetate in patients with castrationā€resistant prostate cancer

Authors :
Rana R. McKay
Lauren C. Harshman
Mary-Ellen Taplin
Lillian Werner
Abhishek Tripathi
Mark Pomerantz
Gwo-Shu Mary Lee
Benjamin L. Maughan
Philip W. Kantoff
Lorelei A. Mucci
Mari Nakabayashi
Xiaodong Wang
Christopher Sweeney
Emmanuel S. Antonarakis
Source :
The Prostate. 77:1303-1311
Publication Year :
2017
Publisher :
Wiley, 2017.

Abstract

Background Statins compete with DHEAS for influx through the SLCO2B1 transporter, which may prolong time to progression (TTP) on androgen deprivation therapy. Abiraterone acetate (AA) may also undergo SLCO-mediated transport. Based on preclinical findings showing antagonism, we hypothesized that statins may compete with AA for influx via SLCO2B1 and could negatively impact drug efficacy. Methods We queried two institutional clinical databases (Dana-Farber Cancer Institute [DFCI], Johns Hopkins University [JHU]) for CRPC patients treated with AA. Treatment duration was a surrogate for TTP. Associations between statin use and AA duration were estimated using the Kaplan-Meier method. Multivariable Cox regression modeling adjusted for known prognostic factors. Results Of the 224 DFCI and 270 JHU patients included, the majority (96%) had metastatic disease. Nearly half (41% and 45%) were statin users. In the DFCI cohort, there was a trend toward longer AA duration in statin users: 14.2 versus 9.2 months (HR 0.79, 95%CI: 0.57-1.09, P = 0.14). There was no association between statin use and AA duration in the JHU cohort: 8.3 versus 8.0 months (HR 0.89, 95%CI: 0.69-1.16, P = 0.38) in the statin users versus non-users, except for a trend in patients that had not previously received docetaxel or enzalutamide (HR 0.79; 95%CI: 0.57-1.10). Conclusions Contrary to our initial hypothesis, there was a trend toward longer (rather than shorter) AA duration in statin users in the entire DFCI cohort and in the enzalutamide- and docetaxel-naive JHU patients. Together, these results do not support the hypothesis that statins interfere with AA efficacy.

Details

ISSN :
10970045 and 02704137
Volume :
77
Database :
OpenAIRE
Journal :
The Prostate
Accession number :
edsair.doi.dedup.....0cc15b1efb50be20ba767b4fd73642a0