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

Abstract

Abstract. The aim of the present retrospective study was to evaluate the efficacy and safety of diethylstilbestrol (DES) as treatment for patients with castration-resistant prostate cancer (CRPC) and to identify predicting factors of response to DES. Patients treated with DES during the castration-resistant phase following the failure of prior treatment with LH-RH analogs during the castration-sensitive phase were retrieved from a prostate cancer database of our institution. Patients were treated with a daily dose of DES of 1-4 mg (mean, 2.6 mg) and anticoagulants for thromboembolic prophylaxis until disease progression. We analyzed their medical records, biochemical prostate-specific antigen (PSA) response and time to disease progression (TDP). Disease response and progression were identified according to the PCWG2 criteria. Patient data were examined using Kaplan-Meier survival analysis and statistical correlation tests with intra-patient comparison of the LH-RH and DES treatment phases. Fortythree DES-treated CRPC patients were found in our database through July 2011. The median age was 66 years. Sixty-three percent of the patients achieved a ≥50% decline in their serum PSA levels during DES therapy. Median TDP was 20.4 months for LH-RH analog treatment in the castration-sensitive phase, and 7.1 months for DES treatment in the castration-resistant phase. Durable responses (>1 year) were observed in 31% of the patients. Median overall survival was 57 months from the start of the DES therapy. There was no significant correlation between the TDP under LH-RH analogs and under DES therapy among the 38 patients eligible for correlation analysis. However, the magnitudes of serum PSA responses under DES and LH-RH analogs were significantly correlated with each other, and with the TDP under DES therapy. There were no treatment-related deaths. Four patients (9%) developed thromboembolic complications while under treatment, some of which appeared to be related to a discontinuation of thromboprophylaxis. In conclusion, DES confers substantial clinical benefit in the treatment of CRPC, with a relatively good safety profile when administered with thromboprophylaxis. The use of DES may be effective in CRPC, irrespective of the length of the hormone-sensitive period with LH-RH treatment. The magnitude of PSA response to previous treatment with LH-RH analogs, as well as to DES, was predictive of the duration of response to DES.

Continuous prostate-specific antigen rise despite salvage radiotherapy following radical prostatectomy: Pattern of clinical relapse and predictive factors

“…The addition of systemic therapy appears to be necessary to address the issue of distant micrometastases, e.g. endocrine, cytotoxic or immune therapy (21)(22)(23)(24)(25).…”

Diethylstilbestrol can effectively accelerate estradiol-17-O-glucuronidation, while potently inhibiting estradiol-3-O-glucuronidation

“…However, human exposure to this chemical still occurs in clinics. It is now still used in hormone replacement therapy for women, and is also accepted as an efficient therapy for prostate (Grenader et al, 2014) and breast cancers (Peethambaram et al, 1999).…”

“…However, human exposure to this chemical still occurs in clinics. It is now still used in hormone replacement therapy for women, and is also accepted as an efficient therapy for prostate (Grenader et al, 2014) and breast cancers (Peethambaram et al, 1999).Our previous studies demonstrated that DES acts as a good substrate to multiple UDP-glucuronosyltransferases (UGT), including UGT1A1, 1A3, 1A8 and 2B7, with high affinity (Zhu et al, 2012). It appeared that DES may possibly inhibit many UGT isoforms.…”

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 .…”