Complete Remission of Hormone Refractory Adenocarcinoma of the Prostate in Response to Withdrawal of Diethylstilbestrol

Abstract

The phenomenon of regression of adenocarcinoma of the prostate after the withdrawal of antiandrogens is well documented. However, to our knowledge we report the first case of durable complete remission of hormone refractory prostate cancer after cessation of diethylstilbestrol. The drug was discontinued because the patient had disease progression while on diethylstilbestrol and withdrawal resulted in durable remission. In more than 3 years of followup since discontinuing diethylstilbestrol there has been no evidence of clinical or biochemical recurrence.

Molecular basis for the antiandrogen withdrawal syndrome

“…In some patients with prostate cancer who manifested disease progression during CAB therapy, discontinuation of antiandrogen treatment might result in a significant fall in serum PSA, often correlated with clinical improvement. This withdrawal response was first reported with flutamide [Kelly and Scher, 1993], but similar phenomena have been observed after cessation of other non‐steroidal antiandrogens, including bicalutamide [Small and Carroll, 1994] and nilutamide [Huan et al, 1997] or steroidal antiandrogens such as cyproterone acetate [Sella et al, 1998] and chlormadinone acetate [Akakura et al, 1995], as well as a semi‐synthetic estrogen diethylstilbestrol [Bissada and Kaczmarek, 1995] and a progestational agent megestrol acetate [Dawson and McLeod, 1995]. Therefore, what initially was called “flutamide withdrawal syndrome” was renamed “antiandrogen withdrawal syndrome” or even more recently “steroid hormone withdrawal syndrome” [Kelly et al, 1997].…”

From estrogen to androgen receptor: A new pathway for sex hormones in prostate

“…Estrogens are still at times used to repress androgens, and currently provide a very favorable cost profile compared with any other means of androgen ablation. Many clinical trials have suggested that E2 would be less effective than DES (26,27) when used to treat prostate cancer. Our findings that E2, but not DES, can activate androgen-target genes in the prostate (Fig.…”

Antiandrogen withdrawal in castrate‐refractory prostate cancer

“…16 Although improvements in cancer-related anemia, pain palliation, and radiographic regression of measurable disease have been documented, PSA declines have been most commonly detected. In addition to antiandrogens, withdrawal responses in prostate cancer patients have been documented after their cessation of megestrol acetate, 17,18 diethylstilbestrol, 19 13-cis-retinoic acid, 20 and estramustine. 21 In general, withdrawal responses occur several weeks after drug withdrawal; however, bicalutamide, which has a relatively long serum half-life, may not have evident withdrawal responses until 6 to 8 weeks after ceasing administration of this medication.…”