Objectives: Diethylstilbestrol administration was a classic form of androgen deprivation therapy (ADT) that gradually fell out of favor because of its cardiovascular toxicity, economic disinterest on the part of manufacturers, and the emergence of novel therapeutic agents with a superior safety profile. The cost of contemporary agents and the efficacy of diethylstilbestrol (DES) have perpetuated the evaluation of this agent, especially in the circumstance of early hormone-refractory (clinical stage D2.5) disease. The objective of this study is to evaluate the status of DES-based therapies, and assess their efficacy and toxicity as a viable form of ADT.
Methods: Current research from single-institution and group studies, as well as basic scientific investigations related to DES, were assessed with regard to the population studied, dosage, criteria for response, response rate, duration of response, and toxicity.
Results: Contemporary basic research has demonstrated a direct apoptotic effect of DES on prostate cancer cells. There is also evidence to support the ability of DES to suppress testosterone production at extratesticular sites and inhibit dihydroepiandrosterone sulfate serum levels. Contemporary cooperative group trials for stage D2 disease incorporating a DES arm have demonstrated therapeutic efficacy and equivalence to orchiectomy, which is marred by significant cardiovascular toxicity. In smaller single-institution studies (n = 17 to 38) of patients with D2.5 disease, an average response rate of 55% is noted with a mean time to clinical progression of 6.4 months (2 to 18). Cardiovascular toxicity occurred in 10% to 30% of patients, with events including deep vein thrombosis, myocardial infarction, and transient ischemic attack. Edema and gynecomastia was also noted. Strategies to reduce thromboembolic events, such as dose reduction or the use of warfarin sodium were unsuccessful, whereas the use of low-dose aspirin (100 mg daily) resulted in only 1 of 38 vascular events.
Conclusions: In contemporary studies of DES as an agent for ADT in D2.5 patients, a reasonable response rate (40% to 60%) of modest duration (5 to 8 months) is noted. Cardiovascular complications still persist, requiring the development of safe, effective antithrombolic therapy to take advantage of this phenomenon.