title: Diethylstilbestrol for the treatment of patients with castration-resistant prostate cancer: retrospective analysis of a single institution experience.
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. Forty-three 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.
authors.affiliation: Department of Oncology, Shaare Zedek Medical Center, and Hebrew University-School of Medicine, Jerusalem, Israel.
authors.forename: Tal
authors.initials: T
authors.lastname: Grenader
authors.forename: Yevgeni
authors.initials: Y
authors.lastname: Plotkin
authors.forename: Maya
authors.initials: M
authors.lastname: Gips
authors.forename: Nathan
authors.initials: N
authors.lastname: Cherny
authors.forename: Alberto
authors.initials: A
authors.lastname: Gabizon
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000627:therapeutic use; D004054:Diethylstilbestrol / Q000627:therapeutic use*; D018450:Disease Progression; D004968:Estrogens, Non-Steroidal / Q000627:therapeutic use*; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors; D006801:Humans; D008297:Male; D008875:Middle Aged; D009919:Orchiectomy; D017430:Prostate-Specific Antigen / Q000097:blood; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy* / Q000401:mortality; D011655:Pulmonary Embolism / Q000188:drug therapy*; D012189:Retrospective Studies; D016896:Treatment Outcome; D054556:Venous Thromboembolism / Q000188:drug therapy*
chemical_list: D000925:Anticoagulants; D004968:Estrogens, Non-Steroidal; D007987:Gonadotropin-Releasing Hormone; D004054:Diethylstilbestrol; D017430:Prostate-Specific Antigen