Current role of diethylstilbestrol in the management of advanced prostate cancer

Abstract

What ' s known on the subject? and What does the study add? Diethylstilbestrol (DES) has been found to have anti-tumour properties and clinical effectiveness in prostate cancer that is resistant to the fi rst-line hormonal therapy.This review found that low-dose DES has anti-tumour effi cacy with limited cardiovascular side effects and should be considered for secondary hormone manoeuvres.The aim of this review was to describe the most recent data from contemporary clinical trials of diethylstilbestrol ( DES) to better determine its current role in advanced prostate cancer treatment as new hormonal therapies emerge. Relevant clinical studies using 1 mg of DES in castrate-resistant prostate cancer (CRPC) were identifi ed from the literature, clinical trial databases, websites and conference abstracts. The effi cacy and safety outcomes were summarized. DES in CRPC produced a biological response (change in PSA level) and improved the median survival of patients when used as a second-line hormone therapy after standard androgen deprivation with bicalutamide and LHRH analogues. These fi ndings were for low doses of DES. The 1-mg dose is associated with a reduced toxicity, including fewer thromboembolic and cardiovascular events. Low-dose DES appears to be safe and effective for CRPC before initiating chemotherapy. The cost/effi ciency ratio may encourage physicians to consider DES as a therapy option before chemotherapy in non-symptomatic CRPC.

Diethylstilbestrol for the treatment of patients with castration-resistant prostate cancer: Retrospective analysis of a single institution experience

“…A review by Bosset et al (12) reports that thromboembolic events occur in ~5% of patients receiving DES with thromboprophylaxis. The rate of thromboembolic complications in the present study was 9%, similar to that observed in previous studies (Table II).…”

“…In the 1940s, it became the first hormonal treatment shown to inhibit prostate cancer (9)(10)(11). Following this discovery, the accepted treatments for advanced prostate cancer became orchiectomy and/or DES for the next two decades (11)(12)(13). The Veterans Administration Cooperative Urological Research Group (VACURG) found that DES increased cardiovascular and thrombogenic toxicity at the 5-mg dose.…”

“…The Veterans Administration Cooperative Urological Research Group (VACURG) found that DES increased cardiovascular and thrombogenic toxicity at the 5-mg dose. A slight trend for reduced efficacy at the 1-mg dose, led to the use of 3 mg as the standard dose in patients with metastatic prostate cancer (11,12). Low doses (1-3 mg/day) of DES had fewer cardiovascular side-effects when compared to higher doses.…”

“…Low doses (1-3 mg/day) of DES had fewer cardiovascular side-effects when compared to higher doses. Typically, thromboembolic events occur in ~5% of patients (12,13).…”

In touch with your feminine side: how oestrogen metabolism impacts prostate cancer

“…Huggins reported that exogenous oestrogens had protective properties mediated by a negative feedback effect on the hypothalamic-pituitary-gonadal (HPG) axis which reduced stimulation for androgen secretion from the testes (Huggins & Hodges 1941). Diethylstilbestrol (DES), a synthetic non-metabolised oestrogen, is still used in certain clinics as a non-first line therapy to chemically castrate patients with metastatic prostate cancer (Bosset et al 2012, Clemons et al 2013. DES negatively feedbacks on the pituitary gland to reduce the secretion of luteinising hormone, which reduces the stimulus for the testes to synthesise sex hormones.…”