Diethylstilboestrol for the treatment of prostate cancer: past, present and future (original) (raw)
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Urology, 1998
Objectives. To test the use of 1 mg/day of oral diethylstilbesterol (DES) as a treatment for patients with advanced prostate cancer who had failed primary hormonal therapy. Approximately 40,000 men this year will experience first-line hormonal therapy failure for their metastatic prostate cancer. At this time there is no standard therapy for men whose first-line hormonal manipulation has failed. This clinical problem has been exacerbated by the use of prostate-specific antigen (PSA) as a proved biomarker to follow disease progression. Patients who are experiencing hormonal therapy failure now present with a rising PSA, and virtually all are asymptomatic. The dilemma of how to treat these patients represents a new clinical problem for the medical oncologist and urologist that needs to be answered. Methods. We conducted a Phase II trial of oral DES in 21 patients. Patients were followed for response by PSA criteria and toxicity. A decrease in two serial measurements of PSA of greater than 50% from baseline was judged to be a partial response. Results. Nine of 21 patients achieved a PSA response (43% response rate with 95% confidence intervals of 22% to 64%) leading to early cessation of this Phase II trial. Eight of 13 patients (62%) who had only one prior hormone manipulation that failed demonstrated a PSA response, whereas only 1 of 8 patients (13%) who had received two or more hormone treatments responded (P ϭ 0.07). The median follow-up is 82 weeks (range 8 to 122) among 16 surviving patients. The survival rate at 2 years is 63% (95% confidence interval 41% to 99%).
Current role of diethylstilbestrol in the management of advanced prostate cancer
BJU International, 2012
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.
Oncology Reports, 2013
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.
Beyond castration-defining future directions in the hormonal treatment of prostate cancer
Hormones & cancer, 2012
It is now almost 70 years since Charles Huggins described the relationship between testosterone and the prostate gland. Arguably defining one of the first targeted therapies, the reduction of testosterone to castrate levels remains unaltered as the standard of care for men with metastatic prostate cancer. The failure of castration to permanently control the growth of prostate cancer leads to a state called castration-resistant prostate cancer (CRPC). Whilst numerous mechanisms have been suggested for the emergence of castration resistance [Scher and Sawyers (J Clin Oncol 23(32):8253-8261, 2005); Chen et al. (Curr Opin Pharmacol 8(4):440-448, 2008), Pienta and Bradley (Clin Cancer Res 12(6):1665-1671, 2006); Feldman and Feldman (Nat Rev Cancer 1(1):34-45, 2001); Mostaghel and Nelson (Best Pract Res Clin Endocrinol Metab 22(2):243-258, 2008)], a greater understanding of prostate cancer biology suggests that many such cancers retain a dependency on androgens and endeavour to increase b...
Cureus
Introduction: Prostate cancer is the second most common cancer and the fifth leading cause of death worldwide. Its metastatic stage is associated with considerable morbidity and may lead to death. In Pakistan, given the high levels of economic constraint, patients with castrationresistant metastatic prostate cancer can be treated with cost-effective medications like diethylstilbestrol (DES). Objectives: The goal of this study was to assess the efficacy and adverse effects of DES when used in patients with castration-resistant prostate cancer (CRPC). Materials and methods: From January 2011 to December 2016, all medical records of patients with a diagnosis of prostate cancer resistant to the effects of castration presenting at Shaukat Khanum Cancer Hospital and Research Centre, Lahore, were reviewed. All patients were treated with DES (2.5 mg) initially, but the dose was increased for some patients to 5 mg in combination with aspirin (75 mg). The patients were followed clinically with prostate-specific antigen (PSA) value assessment. The PSA response to treatment, time to disease progression, and adverse events were recorded and analyzed using IBM SPSS Statistics for Windows, Version 20.0 (IBM Corp., Armonk, NY).
British journal of cancer, 2011
The role of further hormone therapy in castration-resistant prostate cancer (CRPC) remains unclear. We performed a multi-centre randomised phase III study comparing the use of Dexamethasone, Aspirin, and immediate addition of Diethylstilbestrol (DAiS) vs Dexamethasone, Aspirin, and deferred (until disease progression) addition of Diethylstilbestrol (DAdS). From 2001 to 2008, 270 men with chemotherapy-naive CRPC were randomly assigned, in a 1 : 1 ratio, to receive either DAiS or DAdS. They were stratified for performance status, presence of bone metastases, and previous normalisation of prostate-specific antigen (PSA) to androgen deprivation. The study end points were the proportion of patients achieving a 50% PSA response, progression-free survival (PFS), overall survival, and quality of life. Intention-to-treat analysis was carried out. The effect of treatment was studied first by Kaplan-Meier curves and log-rank test, and finally through multivariable stratified Cox's proporti...
Are Hormonal Agents Better Than Chemo in Metastatic Castration-resistant Prostate Cancer?
Turkish Journal of Oncology, 2021
In this study, we aim to determine which treatment is more appropriate in castration-resistant chemotherapy-naive patients. Therefore, docetaxel and agents active in the androgen pathway (abiraterone and enzalutamide) were compared retrospectively in patients progressing on ADT. MATERİAL METHOD The study was designed as a retrospective and multi-center study. Patients from 5 centers in Turkey were included in the study. The primary endpoint of the study was ovreall survival and the secondary endpoint was progression-free survival. RESULTS Median overall survival of the chemotherapy group was 18.66 months, it was 16.26 months in the hormonal treatment group. There was no statistically signi cant difference between the groups (p = 0.311). Median progression-free survival of the chemotherapy group was 5.6 months, while it was 9 months in the hormonal therapy group. There was statistically signi cant difference between the groups (p = 0.024). CONCLUSİON There was statistical difference in progression-free survival in favor of hormonal therapies in our study. The difference did not re ect on overall survival and there was no difference between hormonal therapies and docetaxel. Heterogeneity in the selection of patients is considered to lead to this result; however, larger randomized controlled studies are needed to determine the most appropriate treatment in these patients.
Clinical and Translational Oncology, 2019
Background Novel hormonal therapies have been recently investigated in non-metastatic castration-resistant prostate cancer (CRPC). We performed a meta-analysis to assess the efficacy and safety of novel hormonal therapies in non-metastatic CRPC. Materials and methods The primary outcome was metastasis-free survival (MFS). The secondary endpoints were overall survival (OS), time to PSA progression and safety. We planned a subgroup analysis according to the PSA doubling time (> 6 vs < 6 months), Eastern Cooperative Oncology Group (ECOG) performance status (1 vs 0) and concomitant use of bone-targeting agent (yes vs no). Results Pooled analysis of novel hormonal therapies revealed significantly increased MFS compared with placebo (hazard ratio (HR): HR = 0.32, 95% CI 0.25-0.41; p < 0.00001). The subgroup analysis showed a statistically significant MFS advantage in favour of men with the lower ECOG performance status. Other secondary endpoints favoured the novel hormonal therapies. The relative risk (RR) of grade ≥ 3 adverse events and ≥ 3 hypertension was 1.31 and 1.39, respectively. Conclusions This study confirmed the efficacy and safety of the novel hormonal therapies in non-metastatic CRPC.