The impact of statin use on the efficacy of abiraterone acetate in patients with castration-resistant prostate cancer Journal Article
| Authors: | Harshman, L. C.; Werner, L.; Tripathi, A.; Wang, X.; Maughan, B. L.; Antonarakis, E. S.; Nakabayashi, M.; McKay, R.; Pomerantz, M.; Mucci, L. A.; Taplin, M. E.; Sweeney, C. J.; Lee, G. S. M.; Kantoff, P. W. |
| Article Title: | The impact of statin use on the efficacy of abiraterone acetate in patients with castration-resistant prostate cancer |
| 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-naïve JHU patients. Together, these results do not support the hypothesis that statins interfere with AA efficacy. © 2017 Wiley Periodicals, Inc. |
| Keywords: | adult; cancer chemotherapy; aged; middle aged; retrospective studies; major clinical study; overall survival; disease course; drug efficacy; drug potentiation; treatment duration; antineoplastic agents; united states; antineoplastic agent; prostate specific antigen; metabolism; metastasis; cell line; cohort analysis; pathology; retrospective study; time factors; docetaxel; prostate cancer; drug synergism; prostate-specific antigen; disease progression; taxoids; abiraterone acetate; trend study; hydroxymethylglutaryl coenzyme a reductase inhibitor; biological transport; drug use; taxoid; castration resistant prostate cancer; phenylthiohydantoin; hydroxymethylglutaryl-coa reductase inhibitors; transport at the cellular level; organic anion transporters; time factor; electronic health records; duration; cancer prognosis; drug effects; statins; enzalutamide; humans; human; male; priority journal; article; prostatic neoplasms, castration-resistant; analogs and derivatives; statistics and numerical data; electronic health record; organic anion transporter; slco transport; slco2b1 protein, human |
| Journal Title: | Prostate |
| Volume: | 77 |
| Issue: | 13 |
| ISSN: | 0270-4137 |
| Publisher: | John Wiley & Sons |
| Date Published: | 2017-09-15 |
| Start Page: | 1303 |
| End Page: | 1311 |
| Language: | English |
| DOI: | 10.1002/pros.23390 |
| PUBMED: | 28762529 |
| PROVIDER: | scopus |
| PMCID: | PMC5811259 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 4 October 2017 -- Source: Scopus |
