Torgny Nilsson

Treatment of Advanced Prostatic Carcinoma with Estramustine Phosphate (Estracyt

Estramustine phosphate (Estracyt) was used in the treatment of 154 patients with carcinoma of the prostate in stage IV. Sixty-three patients were given Estracyt from the outset (primary treatment group) and 91 had previously received some other endocrine therapy (secondary treatment group). All of the patients were observed for more than one year. The drug was given intravenously and/or orally. Objective remissions occurred in 46 (73.0%) of the 63 patients in the primary treatment group and subjective remissions in all the objective responders and in 12 additional patients (92.0%). The corresponding figures for the secondary treatment group were 28 (30.7%) and 52 (57.1%) of 91. The side-effects were negligible, and the drug was well tolerated. No cumulative toxic effect was observed in patients who had been receiving the treatment for more than five years. In our opinion the compound is valuable in the treatment of advanced prostatic carcinoma (stage IV).

Cardiovascular complications of estrogen therapy for nondisseminated prostatic carcinoma. A preliminary report from a randomized multicenter study.

In a prospective multicenter study, 244 men with highly or moderately differentiated prostatic cancer in stage I, II or III (VACURG) were consecutively randomized to three groups of treatment: Group A (77 patients) received polyestradiol phosphate (Estradurin, Leo) 80 mg i.m. every fourth week + ethinyl estradiol (Etivex, Leo) 150 micrograms daily, group B (72 patients) estramustine phosphate (Estracyt, Leo) 280 mg twice daily, and group C (76 patients) no therapy. Only men without current or previous other malignancy and without cardiovascular disease were admitted to the study. After 4 1/2 years 125 of the 244 patients had left the study, 9 because of cancer progression (stage IV, VACURG). The most serious complications were cardiovascular, including ischemic heart disease, cardiac decompensation, cerebral ischemia and venous thromboembolism, which occurred in 24 patients from group A and 9 from group B as compared to only one patient in group C. The subgroup superficial or deep venous thrombosis comprised 11 group A and 2 group B patients. Estrogens (E + e) offered as palliative treatment to patients with non-generalized prostatic carcinoma is burdened with a high incidence of serious cardiovascular complications.

Estracyt in advanced prostatic carcinoma. Case report.

A 75-year-old man with metastasising prostatic carcinoma was treated with Estracyt® (estradiol-3-N[bis-(2-chlorethyl)]-carbamate-17-dihydrogen phosphate). Histological and cytological examination showed complete regression of some lymph node metastases. Renographic and roentgen examinations revealed regression of other lymph node metastases. The patient felt better, his general condition improved and the indwelling catheter could be removed. Treatment was continued for 2 months during which the patient received a total of 9.5 g Estracyt® i.v. No side effects were observed.

Histochemical and Biochemical Investigation of Advanced Prostatic Carcinoma Treated with Estramustine Phosphate, Estracyt

The activity and distribution of five hydrolytic enzymes in human prostatic carcinomatous tissue were studied before and during treatment with estramustine phosphate, Estracyt, in 13 patients with prostatic carcinoma, stage IV. Seven of the patients had, and 6 had not, received other treatment before the trial. In the previously untreated patients estramustine phosphate induced enzymatic changes similar to those known to be produced by conventional estrogen therapy. Histochemically, estramustine phosphate therapy—in contrast to estrogen therapy—produced an increase in lipofuscin in the biopsy specimens studied, an observation possibly suggesting a cytostatic or cytotoxic effect of the drug. In the previously estrogen-treated patients estramustine phosphate caused some enzymatic changes indicating that the compound has some effect over and above that of the previous treatment.

Enzyme Activity and Distribution in the Hyperplastic and Cancerous Human Prostate

A biochemical and histochemical study of acid phosphatase, alkaline phosphatase, nonspecific esterases, aminopeptidase and β-glucuronidase in human hyperplastic and cancerous prostatic tissue revealed that the quotient between the activities of acid phosphatase and β-glucuronidase in cancerous tissue was only 10% of that in hyperplastic tissue. The difference is probably due mainly to a histochemically demonstrated lower activity of acid phosphatase in the cancerous tissue. In soft tissue metas-tases in 2 patients the acid phosphatase/ β-glucuronidase quotient was of the same magnitude as that in the patients primary prostatic carcinoma. In 2 cases the prostate showed metastases from other organs. In these secondaries the quotient differed considerably from that found in primary carcinomas of the prostate. The above novel observation may be of value in the identification of extra-prostatic metastases.

Histochemical and Biochemical Enzyme Studies in Prostatic Carcinomatous Tissue Before and During Treatment with Estrogen

The activity and distribution of five hydrolytic enzymes in human prostatic carcinomatous tissue were studied before and during treatment with estrogens. The histochemical findings were in accordance with earlier investigations. The treatment markedly suppressed the acid phosphalase activity, but changed the other activities only slightly. The acid phosphatase/β-glucuronidase quotient was about 3 before treatment compared with less than 1 after successful treatment. This decrease might be a sign of a favourable effect of estrogen therapy.

Study of Glomerular and Tubular Function After in Situ Cooling of the Kidney

Ischemia of the kidney for 3 hours at a temperature of 16 to 18C will only impair renal function to a minimal degree measured by glomerular (51Cr ethylenediaminetetracetic acid) and tubular (125I hippuran) clearances. A newly developed device for surface cooling is described. The technique of clinical in situ surface cooling is recommended whenever an ischemia time for more than 10 minutes is expected.

Primary Treatment of Prostatic Carcinoma with Estramustine Phosphate: Preliminary Report

Estramustine phosphate has been used as primary treatment in 38 patients with advanced prostatic carcinoma. Of these 38 patients 36 responded objectively to treatment, regression occurring in 10 patients with soft tissue metastases, 3 with pulmonary metastases and 3 with bony metastases. Primary cytotoxic treatment in patients with far advanced prostatic carcinoma is advocated and a randomized clinical study is suggested.