Efficacy of Testosterone Suppression with Sustained-Release Triptorelin in Advanced Prostate Cancer

Abstract

IntroductionAndrogen deprivation therapy (ADT) is a mainstay of treatment against advanced prostate cancer (PC). As a treatment goal, suppression of plasma testosterone levels to <50 ng/dl has been established over decades. Evidence is growing though that suppression to even lower levels may add further clinical benefit. Therefore, we undertook a pooled retrospective analysis on the efficacy of 1-, 3-, and 6-month sustained-release (SR) formulations of the gonadotropin-releasing hormone (GnRH) agonist triptorelin to suppress serum testosterone concentrations beyond current standards.MethodsData of 920 male patients with PC enrolled in 9 prospective studies using testosterone serum concentrations as primary endpoint were pooled. Patients aged 42–96 years had to be eligible for ADT and to be either naïve to hormonal treatment or have undergone appropriate washout prior to enrolment. Patients were treated with triptorelin SR formulations for 2–12 months. Primary endpoints of this analysis were serum testosterone concentrations under treatment and success rates overall and per formulation, based on a testosterone target threshold of 20 ng/dl.ResultsAfter 1, 3, 6, 9, and 12 months of treatment, 79%, 92%, 93%, 90%, and 91% of patients reached testosterone levels <20 ng/dl, respectively. For the 1-, 3-, and 6-month formulations success rates ranged from 80–92%, from 83–93%, and from 65–97% with median (interquartile range) serum testosterone values of 2.9 (2.9–6.5), 5.0 (2.9–8.7), and 8.7 (5.8–14.1) ng/dl at study end, respectively.ConclusionIn the large majority of patients, triptorelin SR formulations suppressed serum testosterone concentrations to even <20 ng/dl. Testosterone should be routinely monitored in PC patients on ADT although further studies on the clinical benefit of very low testosterone levels and the target concentrations are still warranted.Electronic supplementary materialThe online version of this article (doi:10.1007/s12325-016-0466-7) contains supplementary material, which is available to authorized users.

Effectiveness of three different luteinizing hormone-releasing hormone agonists in the chemical castration of patients with prostate cancer: Goserelin versus triptorelin versus leuprolide

“…The currently established threshold for standard castration is a testosterone level of 50 ng/dL (1.7 nmol/L), and it has been used as a treatment guideline for managing prostate cancer with ADT over 4 decades [10]. The 2016 National Comprehensive Cancer Network (NCCN) guidelines also recommend a 50 ng/dL threshold [11]. The 50 ng/dL threshold has persisted because the limited accuracy of the standard double isotope-derivative dilution assay, which cannot reliably measure serum testosterone concentration of <50 ng/dL [12].…”

Interleukin-6 and Lymphocyte Count Associated and Predicted the Progression of Frailty Syndrome in Prostate Cancer Patients Undergoing Antiandrogen Therapy

“…To date, no studies have evaluated if ADT in PCa patients associates with the progression of frailty syndrome over time, taking into account that ADT in PCa greatly reduce the levels of circulating testosterone sometimes achieving undetectable levels, in order to limit cancer relapses and disease progression [18][19][20] and could accelerate the progression of frailty syndrome. There is a consistent body of evidence that relate testosterone deficiency to systemic inflammatory responses e.g., both animal studies and human studies showed that testosterone deficiency is associated with an increase in pro-inflammatory cytokines and testosterone substitution reduced pro-inflammatory cytokines in patients with coronary artery disease, prostate cancer and diabetes mellitus through the decrease in pro-inflammatory cytokines (IL-1β, IL-6, and TNF-alpha) [21,22].…”

Are all gonadotrophin‐releasing hormone agonists equivalent for the treatment of prostate cancer? A systematic review

“…Different formulations of goserelin are effective at controlling testosterone levels, an effect that has been shown to persist in the long term . Leuprorelin and triptorelin have also been shown to achieve the lower testosterone threshold value of ≤20 ng/dL in >90% of patients in non‐comparative studies , but data on the ability of goserelin to achieve lower testosterone levels are lacking. A recent evidence‐based review highlighted that suppression of testosterone to lower than the historic standard threshold level of <50 ng/dL may have implications for improved disease control and lead to improved clinical outcomes .…”

“…Likewise, triptorelin 1‐, 3‐ and 6‐month formulations suppress testosterone to castration levels (≤50 ng/dL) in >90% of patients from day 29 after the first injection (reviewed in Ploussard and Mongiat‐Artus , and Breul et al. ), and this testosterone suppression is maintained over the long‐term (33 months) . Different formulations of goserelin are effective at controlling testosterone levels, an effect that has been shown to persist in the long term .…”