fosfestrol and Neoplasm-Metastasis

From November 1984 to April 1989, 40 patients with advanced prostate cancer were treated with chemohormonal therapy consisting of orchiectomy, diethylstilbestrol diphosphate, CDDP and cyclophosphamide. Of the 40 patients, 23 had partial response, 15 had stable disease and 2 had progression of disease at 3 months after the initiation of the treatment. In analysis of survival rate, the 5-year survival rate of all cases was 61.5%. The prognosis of the patients with low grade tumors was better than those with high grade tumors. In stages C and D patients, the survival rate was 75%, and 56%, respectively. Relapse occurred in 5 patients. The interval between start of treatment and relapse was approximately 20 months. Relapse rate was lower than that of 23 patients treated with hormonal treatment alone during the same periods (p less than 0.05). Gastrointestinal symptoms including different degrees of nausea and vomiting were observed in about half of the patients. Myelosuppression was seen in a few cases. These findings suggest the effectiveness of chemohormonal therapy for newly diagnosed advanced prostate cancer.

Topics: Aged; Aged, 80 and over; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Combined Modality Therapy; Cyclophosphamide; Diethylstilbestrol; Humans; Male; Middle Aged; Neoplasm Metastasis; Neoplasm Staging; Orchiectomy; Prostatic Neoplasms; Survival Rate

From 1980 to 1991, 18 patients with pathologically proven stage D1 prostate cancer were treated with sequential hormone and radiation therapy at Cancer Institute Hospital. The patient mean age was 65.5 year old and mean follow-up period was 3.7 years. Diethylstilbestrol diphosphate or chlormadinone acetate was given prior to radiation therapy and 70 Gy of external radiotherapy using linear accelerator was sequentially delivered to the primary lesion in 35 fractions. Hormone therapy was continued following radiation therapy. Complete flattening of the primary lesion on digital examination was achieved in all cases. Complications of the treatment were minimal and transient. Tumor progression was observed in 4 cases and 2 of them died of cancer. Five-year non-progression rate, 5-year overall survival rate, 5-year disease specific survival rate and cancer death rate were 65%, 68%, 82% and 50% respectively. Prognoses of the patients with poorly differentiated cancer were worse than those with more differentiated cancer. Sequential hormone and radiation therapy for patients with stage D1 prostate cancer improved the patients' survival almost comparable to those of patients with stage C disease.

Topics: Adenocarcinoma; Aged; Chemotherapy, Adjuvant; Chlormadinone Acetate; Diethylstilbestrol; Follow-Up Studies; Humans; Male; Middle Aged; Neoplasm Metastasis; Neoplasm Staging; Prognosis; Prostatic Neoplasms; Survival Rate

Prostata cancer is one of the most dangerous tumours occurring in the older man. No general accepted therapy has existed up to now. In this study we were engaged on the pharmacokinetics of fosfestrol (Honvan) after oral administration. Its active principle is E-diethylstilbestrol (E-DES), the main metabolite. 250-1600 ng/ml E-DES are measurable after 60-110 min in the plasma of 11 patients suffering from metastatic prostata cancer who have been administered 360 mg fosfestrol orally. This range is equivalent to E-DES concentrations in plasma of 1-4 x 10(-6) mol/l. Thus that E-DES concentration range (5 x 10(-6) mol/l) is nearly attained for a short time to the concentration which hinders the mitosis of human breast cancer cells. Surprisingly similar but not higher concentration - time courses may be measured after a bolus infusion of 360 mg fosfestrol (lasting 45 min). Furthermore, E-DES-glucuronide, E-DES-sulphate and the mixed E-DES-glucuronide-sulphate could be observed in plasma after oral administration. In spite of the high sensitivity of the analytical method (limit of detection for fosfestrol 0.1 micrograms/ml and for E-DES and its mono-conjugates 2-5 ng/ml) neither fosfestrol nor E-DES-monophosphate are detectable in plasma due to the biotransformation of fosfestrol, which is already metabolized by the enzymes of the gut wall. Both phosphates only exist in plasma after intravenous infusion. Further investigations are linked with the question if phase II-conjugates of E-DES can eventually be prodrugs delivering E-DES by cleavage of the ester bonds.

Topics: Administration, Oral; Aged; Androgen Antagonists; Antineoplastic Agents; Biological Availability; Biotransformation; Carcinoma; Chemical Phenomena; Chemistry; Diethylstilbestrol; Estramustine; Estrogens; Humans; Ketoconazole; Male; Middle Aged; Neoplasm Metastasis; Pituitary Hormone-Releasing Hormones; Prostatic Neoplasms; Protein Binding

Nine men with histologically confirmed stage D cancer of the prostate were evaluated with serial serum testosterone levels after being treated with bilateral orchiectomy or intravenous estrogen. Bilateral orchiectomy produced castrate serum testosterone levels (less than or equal to 50 ng. per 100 ml.) within 2 to 6 hours (mean 3 hours) after surgery. Intravenous estrogen therapy did not consistently produce castrate serum testosterone levels immediately but did significantly decrease testosterone within 12 hours after infusion. Both forms of therapy are safe, produce a clinically effective response and offer advantages for patients with advanced prostatic cancer.

Topics: Adenocarcinoma; Aged; Antineoplastic Agents; Castration; Diethylstilbestrol; Humans; Male; Middle Aged; Neoplasm Metastasis; Prostatic Neoplasms; Testosterone; Time Factors

A homogeneous ion pair extraction technique enables the nearly quantitative isolation of fosfestrol (1) (Honvan) and up till now of three of its metabolites from the plasma of patients suffering from metastatic prostata cancer. The detection occurs by HPLC with UV-detector. The range of detection is in the lower microgram range. It is the first time that plasma levels of 1 and its monophosphate (2) can be measured.

Topics: Aged; Antineoplastic Agents; Chromatography, High Pressure Liquid; Diethylstilbestrol; Humans; Injections, Intravenous; Male; Neoplasm Metastasis; Prostatic Neoplasms; Stereoisomerism

Combined chemohormonal therapy of metastatic prostate cancer has not been previously evaluated in patients failing primary hormones (estrogens and/or orchiectomy). The combination of Adriamycin and high-dose diethylstilbestrol diphosphate (Stilphostrol) was studied in 19 heavily pretreated patients, to document toxicity and patient acceptability. Major toxicity was myelosuppression, cardiac failure and venous thrombosis. Clinical improvement was noted in 10/16 (63%) of evaluable patients. Patients with pre-existing cardiac disease or venous thrombosis are not suitable for this therapy.

Topics: Aged; Diethylstilbestrol; Doxorubicin; Drug Therapy, Combination; Heart Arrest; Humans; Leukocyte Count; Male; Middle Aged; Neoplasm Metastasis; Pilot Projects; Prognosis; Prostatic Neoplasms; Thrombophlebitis

Since 1972 in the Urology Department at Darmstadt Hospital the Honvan-high-dose-therapy of 130 patients with metastatic prostatic carcinoma has been carried out under standardizing condition. The analysis shows that there is no significant difference between the patients with prophylaxis against thrombosis (Macrodex and Dihydergot-Heparin) and without prophylaxis. The patients with anti-thrombotic prophylaxis demonstrated significantly higher incidence of reversible elevation of transaminases. The effect of Heparin is probably responsible for this.

Topics: Aged; Antineoplastic Agents; Diethylstilbestrol; Humans; Male; Neoplasm Metastasis; Prostatic Neoplasms; Retrospective Studies; Thromboembolism

Topics: Adenocarcinoma; Aged; Diethylstilbestrol; Humans; Male; Neoplasm Metastasis; Prostatic Neoplasms; Pulmonary Embolism

Diethylstilbestrol diphosphate (DES-P) has shown effective symptomatic relief in patients with metastatic carcinoma of the prostate. Although there is little known about its role in soft tissue metastasis, our experience in 3 patients with advanced carcinoma of the prostate infiltrating the trigone and ureterovesical junction revealed significant improvement of hydronephrosis. All patients failed to respond to conventional doses of stilbestrol. Diethylstilbestrol diphosphate is recommended in the treatment of advanced carcinoma of the prostate with soft tissue metastasis. It is safe and effective, and the tumor responses outweigh the side effects of the drug. The mechanism of action of this compound is discussed.

Topics: Aged; Bone Neoplasms; Carcinoma; Diethylstilbestrol; Humans; Hydronephrosis; Male; Middle Aged; Neoplasm Metastasis; Prostatic Neoplasms

Topics: Acid Phosphatase; Chlorotrianisene; Diethylstilbestrol; Humans; Injections, Intravenous; Male; Neoplasm Metastasis; Neoplasms; Palliative Care; Prostatectomy; Prostatic Neoplasms; Toxicology; Urination Disorders