Plasma and tumour concentrations of
estramustine,
estromustine,
estradiol and
estrone, the major metabolites of
estramustine phosphate (
estracyt), were determined in patients with prostatic
carcinoma treated between one and nine years with repeated oral doses of
estracyt (560 to 840 mg./day). The last dose was given 12 to 16 hours before sampling. The binding of radioactive
estramustine and
estromustine was determined in the tumour tissue to examine the possible role of
estramustine-binding protein for the accumulation of these metabolites into the tumour. Comparison was made with benign prostate hyperplastic tissue from untreated patients.
Estromustine was the main metabolite in plasma as well as in the tumour (range 235 to 450 and 205 to 485 ng./gm., respectively), whereas
estramustine (20 to 45; 95 to 370),
estrone (62 to 140; 63 to 160) and
estradiol (8 to 15; 7 to 36) were found in lower concentrations. Interestingly the concentration of
estramustine was as an average six times higher in the tumour than in plasma contrasting with the other metabolites which were present in equal amounts of the two localities. Binding of 3H-estramustine and 3H-estromustine was two to three times higher in the tumour than in benign hyperplastic tissue and negligible in plasma samples. The present study is the first where substantial amounts of cytotoxically active
estramustine and
estromustine are demonstrated in tumour tissue from
estracyt treated patients. Our findings suggest a mechanism for selective uptake of these metabolites in
prostatic cancer (
estramustine-binding protein). The uptake and binding of
estramustine and
estromustine in the tumour may account for the clinical effects of
estracyt in prostatic
carcinoma.