Effect of dutasteride in men receiving intermittent androgen ablation therapy: The AVIAS trial

Abstract

Cite as: Can Urol Assoc J 2014;8(11-12):e789-94. http://dx.doi.org/10.5489/cuaj.2332 Published online November 24, 2014. Abstract Introduction:We studied the effect of dutasteride on the length of the off-treatment period in prostate cancer patients on intermittent androgen deprivation (IAD) therapy. Methods: We conducted a randomized, placebo-controlled Phase II trial in men with localized prostate cancer and a rising prostatespecific antigen (PSA) level post-primary treatment. Patients were randomized to dutasteride (0.5 mg/day) or placebo. All patients received androgen deprivation therapy (ADT), which was stopped at month 9 if the PSA level was <1.0 ng/mL. ADT was resumed when PSA increased to ≥5.0 ng/mL. End points included time off treatment, PSA nadir after 9 months of ADT, serum testosterone and dihydrotestosterone levels, and time to castrate-resistant prostate cancer (rising PSA while testosterone levels remain <50 ng/mL). Results: There were 87 evaluable patients: 49 dutasteride, 38 placebo. In total, 80 patients completed one treatment cycle: 45 dutasteride, 35 placebo. The median time off treatment for patients reaching ≥5 ng/mL was 18.6 and 16.7 months for dutasteride and placebo, respectively (p = 0.7600). The median PSA nadir at 9 months was 0.1 and 0.075 ng/mL, respectively (p = 0.4486). There were no cases of androgen-independent prostate cancer. Our study limitations include its short duration with only one treatment cycle evaluated. Conclusions: This small-scale Phase II randomized controlled trial showed no benefit to the addition of dutasteride to an IAD regimen.

The effect of 5 alpha-reductase inhibitor therapy on prostate cancer detection in the era of multi-parametric magnetic resonance imaging

“…Previous studies have also investigated the clinical use of 5-ARIs to chemoprevention 6–9,23 . Two landmark studies, the PCPT (Prostate Cancer Prevention Trial) 23 and the REDUCE trial 6 , demonstrated a significant chemopreventive effect of 5-ARIs on the reduction of cumulative PCa incidence.…”

“…5-ARIs are known to be associated with a 25% reduction in the overall prostate volume after 3 to 6 months of exposure 5 . Previous studies have investigated the expanded clinical use of 5-ARIs in PCa 6–9 . In a large randomized study of 6729 patients (REDUCE [Reduction by Dutasteride of Prostate Cancer Events] trial), Andriole et al .…”

MRI findings in men on active surveillance for prostate cancer: does dutasteride make MRI visible lesions less conspicuous? Results from a placebo-controlled, randomised clinical trial

“…Conversely, the AVIAS trial [ 5 ] was a small-scale phase II randomised controlled trial that showed no benefit to the addition of dutasteride to an intermittent androgen deprivation therapy regimen.…”

Cardiovascular Safety and Possible Benefit of a 5-Alpha Reductase Inhibitor among Benign Prostatic Hyperplasia Patients, A Nationally Representative Cohort of Korean Men

“…Evidence suggests CVD risk may be due to mechanisms involving activation of GnRH receptors found in T lymphocytes [22] and increased levels of FSH [23] by GnRH agonists, while clear mechanisms linking lowered DHT levels and CVD risk are unclear. Second, the magnitude of DHT suppression by ADT is greater than that by 5ARI treatment [2,3,18,24], which suggests the excessive suppression of DHT by ADT may have caused the increased risk.…”