Diethylstilboestrol (1 mg) in the Management of Castration-Resistant Prostate Cancer

Abstract

Objective: To investigate the efficacy of diethylstilboestrol (DES) in patients with advanced prostate cancer refractory to androgen suppression. Methods: This retrospective study comprises 194 patients with prostate cancer treated with DES (1 mg daily) between 1976 and 2010. Study outcome parameters included demographic data, tumour characteristics, treatment history, prostate-specific antigen (PSA) responses, radiologic studies, adverse events and overall survival. Results: At initiation of oestrogen therapy the mean patient age was 69 years (range: 48-89) and the median PSA was 96 ng/ml (range: 1.9-9,500). The median duration of prior prostate cancer treatment was 29 months (range: 1-365). DES was the second-line treatment in 58 patients and the third/fourth-line therapy in 136 men. A formal (≥50%) PSA response was observed in 95 patients (48.9%) and the median time to progression (TTP) was 250 days (95% CI, 180-360) for this group. An additional 62 patients (31.9%) had a partial PSA response with a median TTP of 150 days (95% CI, 92-180). Thirty-seven patients (19.1%) did not have a PSA response and the median TTP was 90 days (95% CI, 90-97). The median overall survival from the start of oestrogen therapy for the entire cohort was 576 days (95% CI, 482-690). The median overall survival of patients who had a formal (≥50%), partial (<50%) and no PSA response was 756 (95% CI, 670-1,429), 428 (95% CI, 340-630) and 329 (95% CI, 287-510) days, respectively. Thirty-nine patients (20.1%) were still alive at the end of the study. No treatment-related deaths occurred. Conclusions: In the age of chemotherapy this study highlights the efficacy of oestrogen therapy in castration-refractory prostate cancer. The optimal point in the therapeutic pathway at which DES should be prescribed remains to be established.

Testosterone Replacement Therapy in Hypogonadal Men Following Prostate Cancer Treatment: A Questionnaire-Based Retrospective Study among Urologists in Bavaria, Germany

“…After 8 decades of clinical utility and despite new therapeutic options prior to chemotherapy (e.g. abiraterone, enzalutamide, orteronel, immunotherapy and targeted therapies), the applicability of diethylstilbestrol may be still considered, as a very recent publication suggested [8] . Since testosterone suppression is regarded as a therapeutic option, testosterone supplementation is seen as contraindicated for patients with PCa because androgen depletion is meant to reduce tumor growth, whereas testosterone may support tumor progression.…”

Cytochrome P450 17A1 Inhibitor Abiraterone Acetate Counteracts the Heat Shock Protein 27's Cell Survival Properties in Prostate Cancer Cells

“…This implicates the necessity of targeting additional molecular pathways in prostate cancer (PC). PC progression is usually accompanied with the loss of physiological paracrine androgen dependence, often related with a shift to autocrine supply with androgens, and an increase of further factors being important for tumor growth and survival [9,10]. Moreover, mCRPC showed higher testosterone and dihydrotestosterone concentrations as well as a significantly induced cytochrome P450 17A1 (CYP17A1) expression within the tumour [1,11,12].…”

Circulating oestrogen receptor mutations and splice variants in advanced prostate cancer

“…Other sex steroid receptors, including the oestrogen receptors (ERs; including ESR1 /ERα and ESR2 /ERβ), are also expressed by prostate cancer cells. Therapies targeting ERs have been shown to be active in advanced prostate cancer . While it is not yet known whether ER mutants and splice variants contribute to the progression of prostate cancer, ESR1 missense substitution mutations affect the function of the transcribed ERα ligand‐binding domain, disrupting the normal hormone signalling pathway .…”