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The impact of statin use on the efficacy of abiraterone acetate in patients with castrationāresistant prostate cancer
- 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.
- Subjects :
- Male
0301 basic medicine
Oncology
Time Factors
Abiraterone Acetate
Organic Anion Transporters
Docetaxel
Pharmacology
Androgen deprivation therapy
Efficacy
Prostate cancer
chemistry.chemical_compound
0302 clinical medicine
Electronic Health Records
Abiraterone acetate
Drug Synergism
Middle Aged
Prostatic Neoplasms, Castration-Resistant
030220 oncology & carcinogenesis
Benzamides
Cohort
Disease Progression
Taxoids
medicine.drug
medicine.medical_specialty
Statin
medicine.drug_class
Urology
Antineoplastic Agents
Article
Cell Line
03 medical and health sciences
Internal medicine
Nitriles
Phenylthiohydantoin
medicine
Humans
Enzalutamide
Aged
Retrospective Studies
business.industry
Biological Transport
Prostate-Specific Antigen
medicine.disease
United States
030104 developmental biology
chemistry
Hydroxymethylglutaryl-CoA Reductase Inhibitors
business
Subjects
Details
- ISSN :
- 10970045 and 02704137
- Volume :
- 77
- Database :
- OpenAIRE
- Journal :
- The Prostate
- Accession number :
- edsair.doi.dedup.....0cc15b1efb50be20ba767b4fd73642a0