Statin Use at Start of Androgen-Deprivation Therapy Increases Time to Progression During Androgen-Deprivation Therapy in Prostate Cancer
Statin use has been associated with improved outcome in prostate cancer. In a study reported in JAMA Oncology, Harshman et al found that statin use at the time of initiation of androgen-deprivation therapy was associated with prolonged time to progression during androgen-deprivation therapy in men with hormone-sensitive prostate cancer. The potential mechanism of this effect may be statin competitive inhibition of dehydroepiandrosterone sulfate (DHEAS) uptake.
Androgen-deprivation therapy for biochemical or metastatic recurrence or new metastatic disease between January 1996 and November 2013 showed that 283 men (31%) were taking statins at the start of androgen-deprivation therapy. After a median follow-up of 5.8 years, 644 patients (70%) had disease progression while receiving androgen-deprivation therapy, with a median time to progression during androgen-deprivation therapy of 20.3 months. Median time to progression was 27.5 months (95% confidence interval [CI] = 21.1–37.7 months) in statin users vs 17.4 months (95% CI = 14.9–21.1 months) in nonusers (P < .001).
After adjusting for predefined prognostic factors including biopsy Gleason score, type of primary therapy, use of prior androgen-deprivation therapy along with localized therapy, metastatic status, and prostate-specific antigen level at initiation of androgen-deprivation therapy, statin use remained a significant predictor of reduced risk of progression (adjusted hazard ratio [HR] = 0.83, P = .04). The positive effect of statin treatment was observed among patients with (adjusted HR = 0.84, 95% CI = 0.67–1.06, for M1 disease) and without metastases (adjusted HR = 0.79, 95% CI = 0.58–1.07, for M0 disease; P = .72 for interaction).
The investigators concluded: “Statin use at the time of [androgen-deprivation therapy] initiation was associated with a significantly longer [time to progression] during [androgen-deprivation therapy] even after adjustment for known prognostic factors. 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 [time to progression] in statin users.”
Philip W. Kantoff, MD, of Dana-Farber Cancer Institute, is the corresponding author of the JAMA Oncology article.
The study was supported by the Dana-Farber Prostate Cancer SPORE and Department of Defense. Aaron M. Kantoff is Vice President of Apple Tree Pharmaceuticals, which is an investor in Tokai Pharmaceuticals.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
