Breul Jürgen, Lundström Eija, Purcea Daniela, Venetz Werner P, Cabri Patrick, Dutailly Pascale, Goldfischer Evan R
Loretto Hospital, Freiburg, Germany.
Debiopharm International SA, Lausanne, Switzerland.
Adv Ther. 2017 Feb;34(2):513-523. doi: 10.1007/s12325-016-0466-7. Epub 2016 Dec 27.
Androgen 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.
Data 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.
After 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.
In 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.
雄激素剥夺疗法(ADT)是晚期前列腺癌(PC)治疗的主要手段。作为治疗目标,将血浆睾酮水平抑制至<50 ng/dl已确立数十年。然而,越来越多的证据表明,抑制至更低水平可能会带来更多临床益处。因此,我们对促性腺激素释放激素(GnRH)激动剂曲普瑞林的1个月、3个月和6个月缓释(SR)制剂抑制血清睾酮浓度超过现行标准的疗效进行了汇总回顾性分析。
汇总了9项以血清睾酮浓度为主要终点的前瞻性研究中920例男性PC患者的数据。年龄在42 - 96岁的患者必须符合ADT条件,并且要么未接受过激素治疗,要么在入组前经过了适当的洗脱期。患者接受曲普瑞林SR制剂治疗2 - 12个月。该分析的主要终点是治疗期间的血清睾酮浓度以及总体和每种制剂的成功率,基于20 ng/dl的睾酮目标阈值。
治疗1、3、6、9和12个月后,分别有79%、92%、93%、90%和91%的患者睾酮水平<20 ng/dl。对于1个月、3个月和6个月的制剂,成功率分别为80 - 92%、83 - 93%和65 - 97%,研究结束时血清睾酮值的中位数(四分位间距)分别为2.9(2.9 - 6.5)、5.0(2.9 - 8.7)和8.7(5.8 - 14.1)ng/dl。
在绝大多数患者中,曲普瑞林SR制剂将血清睾酮浓度抑制至甚至<20 ng/dl。接受ADT的PC患者应常规监测睾酮水平,尽管关于极低睾酮水平的临床益处和目标浓度仍需进一步研究。