Diethylstilbestrol prostate

Note PCa, prostate cancer WM, white male DES, diethylstilbestrol AR, androgen receptor PSA, prostate specific antigen and PAP, prostatic acid phosphatase. 

Haukaas, S.A., Hoisater, P.A. and Kalland, T. (1982). In vitro and in vivo effects of diethylstilbestrol and estramustine phosphate (Estracyte) on the mutagen responsiveness of human peripheral blood lymphocytes. Prostate 3 405-414. 

Diethylstilbestrol continues to be recommended in some centers as one of the agents of last resort when prostate cancer proves refractory to steroid hormones or androgen deprivation therapy has done all it can (1). In a Japanese study in which 16 patients were given a daily intravenous injection of diethylstilbestrol diphosphate 250 mg for 28 days, the short-term response was favorable and the drug was well tolerated (2). 

In a randomized study of men treated hormonally for prostatic cancer (3), cardiovascular adverse effects were reported more often in patients treated with diethylstilbestrol than in those treated with cyproterone acetate. The risk was highest during the first 6 months of treatment. 

Profound hypocalcemia occurred in a patient with osteoblastic metastatic carcinoma of the prostate after treatment with diethylstilbestrol 15 mg/day for 7 days (SED-12,1032) (4). 

The risk of thromboembolic complications when diethylstilbestrol is used in treating prostatic cancer is well documented, but there has been some doubt as to the mechanisms involved. Oral diethylstilbestrol diphosphate 300 mg/day has been compared with LR-RH agonist therapy or no treatment in 35 patients with prostatic cancer (5). Diethylstilbestrol reduced the concentrations of protein S to below the lower limit of normal in 24 of the 35 cases. There was also some reduction in antithrombin III concentrations. These results were consistently confirmed in a follow-up group of eight further patients who took diethylstilbestrol. Since these very low concentrations of protein S are virtually the same as those found in congenital deficiency, it seems likely that this plays a role in the development of cardiovascular complications during diethylstilbestrol treatment. 

Diethylstilbestrol can cause hepatic adenomas and carcinomas in experimental animals (10), and hepatocellular carcinoma has been reported in a man who took a total of 668 g over 12 years for suspected carcinoma of the prostate (11). 

The parenteral formulation diethylstilbestrol diphosphate is less commonly used than the oral formulation. In Japan, 24 elderly patients with advanced relapsed prostatic cancer were treated with high doses supplemented with ethi-nylestradiol (doses unclear) there was some slight therapeutic effect, but there were gastrointestinal symptoms and fluid retention (48). Also in Japan, a few patients with advanced disease were treated using intravenous diethylstilbestrol diphosphate 500 mg/day for 20 consecutive days to a total dose of 10 g the authors conclusion was more positive but adverse events were not specified (49). 

Takezawa Y, Nakata S, Kobayashi M, Kosaku N, Fukabori Y, Yamanaka H. Moderate dose diethylstilbestrol diphosphate therapy in hormone refractory prostate cancer. Scand J Urol Nephrol 2001 35(4) 283-7. 

Pavone-Macaluso M, de Voogt HJ, Viggiano G, Barasolo E, Lardennois B, de Pauw M, Sylvester R. Comparison of diethylstilbestrol, cyproterone acetate and medroxyprogesterone acetate in the treatment of advanced prostatic cancer final analysis of a randomized phase III trial of the European Organization for Research on Treatment of Cancer Urological Group. J Urol 1986 136(3) 624-31. 

Hayashi N, Wada T, Ikemoto I, Oishi Y, Suzuki H, Ueda M. Decrease in anticoagulant factors in patients with prostate cancer treated with diethylstilbestrol diphosphate. Nippon Hinyokika Gakkai Zasschi 2003 94 420-7. 

Hisamatsu H, Sakai H, Kanetake H. High-dose intravenous diethylstilbestrol diphosphate (DES-DP) in the treatment of prostatic cancer during relapse. Nioshinihon J Urol 2002 64 199-202. 

Michinaga S, Ariyoshi A. High-dose intravenous diethylstilbestrol diphosphate therapy for hormone-refractory prostate cancer. Nishinihon J Urol 2002 64 203-5. 

Brooks JJ. Hepatoma associated with diethylstilbestrol therapy for prostatic carcinoma. J Urol 1982 128(5) 1044-5. 

Bailar JC 3rd, Byar DP. Estrogen treatment for cancer of the prostate. Early results with 3 doses of diethylstilbestrol and placebo. Cancer 1970 26(2) 257-61. 

Estrogens Diethylstilbestrol Estradiol Others Advanced, inoperable breast cancer in selected men and postmenopausal women advanced, inoperable prostate cancer in men Cardiovascular complications [including stroke and heart attack-espe-cially in men] many other adverse effects [see Chapter 30]... 

C9. Chang, A., Yeap, B., Davis, T., Blum, R., Hahn, R., et al., Double-blind, randomized study of primary hormone treatment of stage D2 prostate carcinoma Flutamide versus diethylstilbestrol. J. Clin. Oncol. 14, 2250-2257 (1996). 

R9. Robertson, C. N., Roberson, K. M., Padilla, G. M., O Brien, E. T., Cook, J. M., etal., Induction of apoptosis by diethylstilbestrol in hormone-insensitive prostate cancer cells. J. Natl. Cancer... 

Stilboestrol (diethylstilbestrol) is the first synthetic oestrogen its use is confined to androgen dependent cancers (breast, prostate). 

Androgen-dependent carcinoma. Diethylstilbestrol (stilboestrol) is rarely used to treat prostate cancer because of its adverse effects. It is occasionally used in postmenopausal women with breast cancer. Toxicity is common. 

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