fosfestrol and Carcinoma

High dose intravenous stilboestrol has a direct cytotoxic effect on prostatic carcinoma cells. The purpose of this study was to assess subjective and objective responses in a select group of patients with metastatic, hormone-refractory carcinoma of the prostate with severe generalized bone pain in association with symptoms of advanced local disease.. Seventeen patients with metastatic carcinoma of the prostate, who had relapsed following a good initial response to androgen ablation, were treated as inpatients with once daily intravenous injection of 1104 mg diethylstilboestrol diphosphate (Honvan, Asta Medica, Cambridge, UK) for 7 days. The hormone-refractory status was confirmed by castrate serum testosterone levels. All the patients had failed to respond to second-line hormone manipulation and had progressive disease. All the patients had generalized bone pain, 11 also had symptoms of bladder outlet obstruction, 3 had recurrent haematuria and 3 had both. The mean age was 74 years (range 59-83), mean time to chemical relapse (rising PSA) was 29 months (range 1-70), and mean time to clinical relapse was 37 months (range 6-98). The WHO pain score, performance status score, and a patient-specific quality of life (daily living activity) were used as the subjective measures and the serum PSA as an objective marker. All the parameters were recorded before, during and up to three months after treatment.. Two patients had a transient relief of bone pain with the pain score reducing by two points. Overall, the pain and performance scores and the local symptoms did not improve. The PSA level continued to rise in all patients. Despite parenteral pre-medication with pethidine and cyclizine, all the patients suffered nausea and pain following the injection. One patient died on the fifth day of treatment from a myocardial infarction and 4 developed deep vein thrombosis. All the patients required further symptom control measures.. High dose intravenous stilboestrol causes considerable morbidity without any objective or subjective response in the treatment of patients with symptomatic, hormone-refractory metastatic carcinoma of the prostate.

Topics: Aged; Aged, 80 and over; Antineoplastic Agents; Carcinoma; Diethylstilbestrol; Humans; Injections, Intravenous; Male; Middle Aged; Nausea; Pain; Prostatic Neoplasms; Treatment Outcome

From November 1984 to December 1993, 72 patients with newly diagnosed, stage C or D prostate cancer were treated with chemohormonal therapy consisting of CDDP, CPM, diethylstilbestrol diphosphate and orchiectomy. Forty-four of 72 patients (61%) had partial response 3 months after the initiation of the treatment. A good response rate was observed in prostate gland and tumor markers (63% and 81%), but the response rate was poor in bone and other soft tissure metastasis (17% and 18%). Subjective symptoms improved in 82% of the pain, 70% of the infravesical obstruction, 65% of the performance status, and 5% of the body weight. The 5-year survival rate was 66%. The prognosis of the patients with poorly differentiated carcinoma or high Gleason score tumor was poor. Survival rate was no different between stage C and D. Relapse occurred in 16 patients (22%) and tended to occur in the patients with poorly differentiated carcinoma, high Gleason score tumor, stage D2 or stable disease. The survival rate was better, and the relapse rate lower than in the 35 patients with hormonal treatment alone during the same period, but no significant difference was observed between the two groups.

Topics: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Carcinoma; Cisplatin; Cyclophosphamide; Diethylstilbestrol; Humans; Lymphatic Metastasis; Male; Middle Aged; Orchiectomy; Prostatic Neoplasms; Survival Rate

For many years, diethylstilbestrol (DES) and its diphosphate (DESPP; Honvan) have been standard therapies for prostatic carcinoma. The effects of DES, its monophosphate (DESP) and of DESPP on the weights of accessory sex organs of mice and rats, and on the experimental Noble Nb-H and Nb-R prostatic carcinomas of the rat were, therefore, compared. In intact mature mice, all three compounds led to a strong and dose-dependent inhibition of seminal vesicle weights and testosterone levels, whereas only a slight antiandrogenic activity in castrated mice was found. In intact rats, DES, DESP and DESPP strongly inhibited accessory sex organ weights and testosterone levels. In castrated rats, however, no antiandrogenic activity was determinable. The prostate carcinoma-inhibiting effects of DES and DESPP were tested in comparison with castration in the transplantable hormone-sensitive Nb-H and Nb-R prostatic carcinoma in rats. Whereas castration caused only a retardation of tumor growth, DES and DESPP (3 x 0.1 mg/kg and 1.0 mg/kg weekly s.c.) led to an almost complete inhibition, which was significantly (P less than 0.01) better than the effect of castration. As the weights of accessory sex organs were identically reduced by either castration or the estrogens, a direct tumor-inhibiting effect of DES and DESPP in addition to their testosterone-lowering activity is obvious. This was proved in an experiment with castrated rats. The only slightly inhibitory activity of castration was strongly potentiated by concomitant administration of DES. Moreover, histological examinations revealed that Nb-H and Nb-R tumors were much more damaged by treatment with DES or DESPP than after castration. Morphometry of the tumors showed that tumor reduction is associated with a decrease in the ratio of the epithelial to the stromal density, i.e. there was an even more pronounced decrease in epithelial cells than that found by merely measuring tumor area. These studies show that the prostate carcinoma-inhibiting effect of DES and DESPP in the Nb model is superior to the effect of castration and that they act directly on the tumor cells used, even in castrated rats.

Topics: Androgen Antagonists; Animals; Carcinoma; Diethylstilbestrol; Genitalia, Male; Male; Organ Size; Prostatic Neoplasms; Rats; Rats, Inbred Strains; Receptors, Androgen; Tamoxifen

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

Two patients, aged 72 and 65 years, each underwent two prostatic resections spaced four and two years apart, respectively. In both cases the earlier procedure showed widespread adenocarcinoma with only occasional endocrine cells, while tissue from the later operations showed prostatic carcinoids. It is suggested that the conventional adenocarcinomas were sensitive to hormonal manipulations used in treatment, but that the originally sparse carcinoid components were resistant to this form of treatment and hence became the predominant tumours. These findings imply that endocrine differentiation in prostatic carcinoma leads to lack of sex steroid sensitivity.

Topics: Adenocarcinoma; Aged; Carcinoma; Cell Transformation, Neoplastic; Diethylstilbestrol; Humans; Male; Prostatic Neoplasms

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: Carcinoma; Diethylstilbestrol; Humans; Male; Prostatic Neoplasms

Topics: Antineoplastic Agents; Carcinoma; Diethylstilbestrol; Humans; Male; Prostatic Neoplasms

Topics: Carcinoma; Diethylstilbestrol; Humans; Male; Neoplasms; Prostatic Neoplasms

Topics: Carcinoma; Diethylstilbestrol; Humans; Male; Prostatic Neoplasms

Topics: Carcinoma; Diethylstilbestrol; Humans; Male; Prostatic Neoplasms