A. Mittelman

Chemotherapy of Advanced, Hormonally Resistant Prostatic Carcinoma

9 advanced prostate cancer patients were given a dose of 1-(2-chlorethyl-3[4-methyl cyclohexyl]-1-nitrosourea) (MeCCNU) 175 mg/m2 orally every 6 weeks. All of them had previously failed on hormonal therapy. 8 patients have progressed during the chemotherapy and only 1 was considered to be stable during a period of 18 weeks. Hematologic toxicity was seen in 3 patients. 21 patients with advanced prostatic carcinoma who failed hormonal therapy were treated with a combination of estracyt (600 mg/m2/day) plus MeCCNU (175 mg/m2/6 weeks) in oral doses. 1 patient had stable disease for about 30 weeks and another one had a subjective response for 12 weeks. 11 patients had hematologic toxicity and 5 of them required dose modification. 10 patients with stage D carcinoma of the prostate were given oral estracyt at a dose of 600 mg/m2/day plus cis-diamminedichloroplatinum (DDP) at an intravenous dose of 60 mg/m2 twice a week repeated every 3 weeks plus methotrexate (MTX) at an i.v. dose of 100 mg/m2 twice a week, repeated every 3 weeks. All of the patients had failed on prior therapy. 9 patients are evaluable, 4 patients had an objective response and 2 others had a subjective response. 2 patients had hematologic toxicity (life threatening) and 2 others had a decrease in creatinine clearance to 60 mg/min and required dose modification. The combination of estracyt + DDP + MTX or a modification seems to be promising.

Combined therapy of advanced prostatic carcinoma with estramustine and prednimustine

We treated 21 patients with stage D prostatic adenocarcinoma who had had unsuccessful hormonal therapy with a combination of 600 mg. per M.2 per day estramustine phosphate (Estracyt) and 15 mg. per M.2 per day prednimustine (Stereocyt, Leo 1031) in daily oral doses. Estramustine is a combination of estradiol and nitrogen mustard, and alone has shown objective responses in advanced prostatic cancer. Prednimustine is an ester of chlorambucil and prednisone. The preliminary results (after 2 to 9 months of therapy) show 5 patients (24 per cent) did not benefit from the drug and 7 patients (33 per cent) are stable. These preliminary results indicate the possible advantage of adding an alkylating agent (prednimustine) to estramustine in advanced prostatic carcinoma. Currently, a national randomized trial by the National Prostatic Cancer Project is evaluating this therapeutic innovation.

Effects of testosterone on estracyt localization in rat prostate.

Testosterone administration to castrated rats leads to increased concentrations of radioactivity associated with estracyt (a conjugate of carbamate with E2) in the prostate gland, particularly the ventral prostate. This contracts with the decreased concentrations of labeled E2. The findings appear to shed further light on the possible mechanism of action of estracyt in cancer of the prostate.

Hypothalamo-Pituitary-Adrenal Axis in Patients with Prostatic Carcinoma

Insulin-induced pituitary growth hormone (GH), adrenocorticotrophic hormone (ACTH) and adrenal cortical response were studied in 12 patients with prostatic carcinoma. 3 patients demonstrated significant abnormal GH release associated with concentrations which remained on a high plateau during the study. 5 patients showed lack of ACTH-cortisol response to insulin-induced hypoglycemia. Those patients subsequently presented clinically with rapidly progressing disease.