Androgen deprivation therapy for prostate cancer

Abstract

Androgen deprivation continues to play a crucial role in the treatment of advanced and metastatic prostate cancer. In the 65 years since its use was first described, urologists and medical oncologists have developed new and innovative ways to manipulate the hypothalamic-pituitary-gonadal axis with the goal of alleviating symptoms and prolonging the life of men with prostate cancer. Despite the successes that androgen deprivation therapy has brought, each method and regimen possesses unique benefits and burdens, of which the clinician and patient must be cognizant. This review discusses the first-line androgen deprivation methods and regimens presently in use with special attention paid to their side effects and the management of them, as well as the question of when to initiate androgen deprivation therapy.Keywords: androgen deprivation , antiandrogen , combined androgen blockade , hormonal therapy , intermittant androgen deprivation , luteinizing hormone releasing hormone , prostate cancer , side effect Expert Opin. Pharmacother. (2008) 9(2):211-228

The Role of ETS Transcriptional Regulation in Hormone Sensitive and Refractory Prostate Cancer

“…Advanced prostate cancer which has become refractory to androgen deprivation (androgen insensitive) is treated by combinatory chemotherapy regimes. Even with treatment, survival rates are poor in patients with advanced refractory prostate cancer (2-24 months) [6,7]. complex resulting in aberrant transcriptional activation and increased expression of cancer promoting gene sets (Fig.…”

“…Current ASCO recommendations for initial treatment of advanced prostate cancer target AR activation through androgen deprivation therapy (ADT) (bilateral orchiectomy, medical castration, or both) [5]. ADT functions by lowering intracellular androgen levels to inhibit AR activation and reduce AR transcriptional activity [6]. However, over 80% of patients undergoing ADT no longer respond to treatment and progress to hormone refractory prostate cancer (HRPC) often within 12-18 months of diagnosis (Fig.…”

Hormonal therapy and chemotherapy in patients with hormone-sensitive prostate cancer

“…АДТ включает хирур-гическую или медикаментозную (агонисты или анта-гонисты лютеинизирующего гормона рилизинг-гор-мона -ЛГРГ) кастрацию с использованием или без использования нестероидных антиандрогенов. Это и есть первая линия лечения пациентов с метастати-ческим РПЖ [3,4]. Чаще всего АДТ позволяет достичь кастрационных значений тестостерона ( 50 нг / дл), и большинство пациентов с метастатическим гормо-ночувствительным РПЖ изначально отвечают на это лечение [5].…”

“…Тем не менее у большинства пациентов будет развиваться устойчивость к этим традиционным гормональным процедурам, а медиана времени до про-грессирования обычно составляет 18-24 мес [6]. По данным разных авторов, более чем в 20-40 % слу-чаев определяется ответ на 2-ю и 3-ю линии гормо-нальной терапии (ГТ), что свидетельствует о сущест-венной роли андрогенового рецептора (АР) в передаче сигнала у больных кастрационно-рефрактерным РПЖ (КРРПЖ) [3][4][5][6][7]. Передача сигнала АР играет цент-ральную роль в биологии РПЖ, необходимую для про-лиферации и выживания раковых клеток [8].…”

Hot flushes in prostatic cancer patients during androgen-deprivation therapy with monthly dose of degarelix or leuprolide

“…1 Gonadotropinreleasing hormone antagonist (GnRH) agonists are currently the standard medical therapy to suppress androgen production. 2 These agents initially bring about strong stimulation of GnRH receptors, which in turn results in an initial surge of testosterone, and microsurges upon repeated injections.…”