Diethylstilbestrol in the Treatment of Castration-resistant Prostate Cancer: A Lower-middle-income Country Experience

Abstract

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 castration-resistant 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). Results: A total of 91 patients were included in the study, and the mean patient age was 66 ± 8 years. The median baseline PSA was 150 ng/mL (range: 56-626 ng/mL), and the median Gleason’s score was eight. A total of 90.1% of patients had metastatic disease at the time of diagnosis. Hormonal ablation was provided with bilateral orchiectomy for 71 patients (78.0%), and luteinizing hormone-releasing hormone (LHRH) analog was provided for 20 patients (22.0%). With this treatment, the median time to PSA progression was 597 days. After DES treatment was started, 78 patients (87.7%) showed a PSA response, and median time to progression was 212 days. In 24 patients (26.4%), the PSA response was maintained for more than a year. The PSA response was quantified as a good response (i.e., ≥50% PSA drop) or as a partial response (i.e., <50% PSA drop). The good PSA response was observed in 56 patients (61.5%) with a median time to progression of 273 days, and 22 patients (24.2%) had a partial response maintained for 109 days. Thirteen patients (14.3%) did not respond to DES treatment. The median percent change in PSA was -55.52% (range: -99.9 to +422). Thromboembolic complication was observed in eight patients (8.7%) patients while two patients suffered from liver toxicity. Conclusion: DES is an effective, economical, and relatively safe drug in patients with CRPC.

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“…This study has limitations associated to its retrospective nature. However, as future directions, low-dose DES, starting from a 1 mg dose, could be studied in prospective randomized studies in comparison to already available later-line treatments, with the intention of finding active therapies that are cost effective for patients and health-care systems, particularly in resource-limited settings such as Mexico and many other LMICs 24 .…”

The androgen receptor inhibits transcription of GPER1 by preventing Sp1 and Sp3 from binding to the promoters in prostate cancer cells

“…In addition to targeting AR activity, it has long been known that estrogens are highly effective at treating advanced PCa [ 11 ]. Despite associated cardiovascular toxicity initially limiting their clinical use [ 11 , 12 ], both estrogen [ 13 , 14 ] and diethylstilbestrol [ 15 , 16 ] have recently been re-investigated in PCa treatment. The tumor suppressive effects of estrogens were originally thought to be facilitated by estrogen receptors ERα and ERβ, but recent research from our lab has identified a third ER, G-protein Estrogen Receptor 1 (GPER1), that plays a critical role in suppressing PCa growth [ 17 ].…”

Are the Effects of DES Over? A Tragic Lesson from the Past

“…In addition, DES was used until 1985, when it was replaced by leuprolide to treat advanced prostate cancer. However, DES is still used in lower and middle-income countries as a treatment for castration-resistant prostate cancer [ 11 ].…”