(Press-News.org) The use of cholesterol-lowering statins when men initiated androgen deprivation therapy for prostate cancer was associated with longer time to progression of the disease, according to an article published online by JAMA Oncology.
The gene SLCO2B1 acts as a transporter that enables a variety of drugs and hormones to enter cells. For example, dehydroepiandrosterone sulfate (DHEAS) is a precursor of testosterone and uses SLCO2B1 to get into cells. Similarly, statins use SLCO2B1 to enter cells as well. Previous research has suggested an association between statin use and improved clinical outcomes for prostate cancer. But little is known about the impact of statin use and response to androgen deprivation therapy (ADT), the cornerstone of treatment for metastatic hormone-sensitive prostate cancer, according to the study background. Conceivably, statins might interfere with the ability of DHEAS to get into cells and thus delay resistance to ADT by this mechanism.
Philip W. Kantoff, M.D., of the Dana-Farber Cancer Institute, Boston, and coauthors examined statin use and time to progression of disease during ADT for prostate cancer.
The authors conducted in vitro studies on prostate cancer cell lines to examine whether statins interfered with DHEAS uptake. Statin use was analyzed in 926 patients who had ADT for prostate cancer between 1996 and 2013.
The authors found in the in vitro studies that statins block DHEAS uptake by competitively binding to SLCO2B1.
Of the 926 patients in the study, 283 (31 percent) were taking a statin when they started ADT. After a median follow-up of nearly six years, 644 patients (70 percent) experienced disease progression while receiving ADT. The overall median time to progression was 20.3 months but men taking statins had a longer median time to progression during ADT compared with nonusers (27.5 months vs. 17.4 months), according to the study.
"Our in vitro finding that statins competitively reduce DHEAS uptake, thus effectively decreasing the available intratumoral androgen pool, affords a plausible mechanism to support the clinical observation of prolonged TTP [time to progression] in statin users," the article concludes.
(JAMA Oncol. Published online May 7, 2015. doi:10.1001/jamaoncol.2015.0829. Available pre-embargo to the media at http://media.jamanetwork.com.)
Editor's Note: An author made a conflict of interest disclosure. The research was funded by the Dana-Farber Prostate Cancer SPORE and by the Department of Defense. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.
Editorial: Progress in Understanding What is Being Statin(ed) in Prostate Cancer
In a related editorial, Jorge D. Ramos, D.O., and Evan Y. Yu, M.D., of University of Washington School of Medicine, Seattle, write: "Harshman et al have made a compelling argument for a biologic mechanism of action of statins in advanced prostate cancer through competitive inhibition of the uptake of DHEAS via SLCO2B1-encoded transporters. However, randomized, prospective validation of the clinical benefits of statin use in advanced prostate cancer is necessary. ... In all, Harshman et al have conducted an interesting analysis linking in vitro preclinical data with retrospective patient outcomes, providing a framework for future evaluation. Nonetheless, the current data are not sufficient to support incorporation of statin use into clinical oncology practice for patients with prostate cancer and additional studies are required."
(JAMA Oncol. Published online May 7, 2015. doi:10.1001/jamaoncol.2015.0833. Available pre-embargo to the media at http://media.jamanetwork.com.)
Editor's Note: Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.
INFORMATION:
Media Advisory: To contact corresponding author Philip W. Kantoff, M.D., call John W. Noble at 617-632-5784 or email johnw_noble@dfci.harvard.edu. To contact corresponding editorial author Evan Y. Yu, M.D., call Leila R. Gray at 206-685-0381or email leilag@uw.edu.
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