estramustine and fosfestrol

Three cases of prostatic carcinoma with palpable metastatic lymph nodes are presented. In case 1, the intrapelvic lymph node metastases were recognized as an abdominal mass. In case 2 and 3, non-regional superficial lymph node metastases were palpable. Orchiectomy and anti-androgen therapy were effective in all cases.

Topics: Adenocarcinoma; Aged; Combined Modality Therapy; Diethylstilbestrol; Estramustine; Humans; Lymphatic Metastasis; Male; Middle Aged; Orchiectomy; Prostatic Neoplasms

Recently, there has been increased interest in the application of preoperative endocrine therapy prior to radical prostatectomy for locally advanced cancer in order to enhance surgical curability and increase survival. Between 1986 and 1993, 40 patients with prostate cancer were given endocrine therapy before radical prostatectomy. Fifteen patients had stage B2 disease and 25 stage C. The median duration of preoperative endocrine therapy was 3.8 months, and all the patients subsequently underwent radical prostatectomy, pelvic lymphadenectomy and castration. There was an average 25.5% (0-71.8%) decreases in the maximal cross-sectional area of the prostate gland as determined by transrectal ultrasonography. Twenty-four of 25 patients with elevated levels of serum prostate-specific antigen (PSA) showed normal values after preoperative endocrine therapy. Evaluation of treatment-related histological effects, divided into three grades, revealed that 17 patients had pronounced, 11 moderate and 12 poor or no regression. Thirteen of the 40 patients (33%) demonstrated pathological downstaging of disease status from the diagnosis made at the initial clinical examination. After a median follow-up period of 36 months (3-100 months), 36 of the 40 patients are disease-free; two died of cancer 43 and 50 months after surgery, respectively. These results suggest that preoperative endocrine therapy may play an important role in the management of locally advanced prostatic cancer.

Topics: Adenocarcinoma; Aged; Antineoplastic Agents; Chlormadinone Acetate; Diethylstilbestrol; Estramustine; Follow-Up Studies; Gonadotropin-Releasing Hormone; Humans; Lymph Node Excision; Male; Middle Aged; Neoplasm Recurrence, Local; Preoperative Care; Prostatectomy; Prostatic Neoplasms

From June 1984 to March 1988, patients with newly diagnosed stage D2 prostate cancer were treated with protocol 1. This comprised oral hormonal agents either diethylstilbestrol diphosphate (Honvan: 300 mg/day) or estramustine phosphate (Estracyt: 560 mg/day), or chlormadinone acetate (Prostal: 100 mg/day), plus intravenous cyclophosphamide (CPM, 0.5-1 g/m2) every 3-4 weeks. From May 1988, protocol 2 was used in a randomized study of castration alone versus castration plus intravenous methotrexate (MTX, 20 mg/m2) every 2 weeks. Forty-nine of 53 patients who underwent the two protocols were evaluable for the response. The response rates according to the NPCP criteria were 92% (11/12) for Honvan, 100% (9/9) for Estracyt, 78% (7/9) for Prostal and castration plus MTX, and 80% (8/10) for castration alone. There were no significant differences among these treatments. The median response duration and survival time (months) were 16 and 44, respectively, for Honvan, 19 and 37 for Estracyt, 12 and 43 for Prostal, 11 and 15 for castration plus MTX, and 13 and 13 for castration alone. The short survival times of the castration alone and castration plus MTX groups were due to a short follow-up period. There were no statistical differences among the oral hormonal agent plus CPM groups. However, the 2-year survival rate (Kaplan-Meier method) was higher in the CPM and MTX groups than in the castration alone group. Survival was longer in the good performance status (P.S.) group than the poor P.S. group (p less than 0.05 by Wilcoxon test) and in the responders than the non-responders (p less than 0.01). Side effects were not excessive in the chemotherapy groups and patient compliance was good.

Topics: Administration, Oral; Aged; Aged, 80 and over; Castration; Chlormadinone Acetate; Combined Modality Therapy; Cyclophosphamide; Diethylstilbestrol; Drug Therapy, Combination; Estramustine; Humans; Infusions, Intravenous; Male; Methotrexate; Middle Aged; Neoplasm Staging; Prognosis; Prostatic Neoplasms; Survival Rate

The present study was designed to investigate the efficacy of various combinations of chemotherapeutic agents in the treatment of prostatic cancer in a group refractory to antiandrogenic therapy (Group 1) and in a previous untreated group (Group 2). Therapeutic combinations of Estracyt (E) + Peplomycin (P) + Doxorubicin (Do) and P + Do + 5 FU (F) in Group 1 and E + P, Honvan (Ds) + P and E in Group 2 were carried out. The main objectives of this study were estimations of the efficacy of E and P in relation to the refractory cases of Group 1 and the efficacy of the combination E + P, in Group 2. This is the first such prospective, randomized, controlled study to be carried out in Japan in relation to prostatic cancer. The results obtained in the present study indicated that chemotherapeutic regimens including E provide some enhanced efficacy, but that the efficacy with regard to refractory cases is poor (23.1-27.3%), as has been reported of studies conducted in the USA and Europe. With regard to previously untreated cases, the E + P regimen achieved a relatively higher response rate than the other treatments (72.7 vs 44.5 or 50.0%). In the comparison of survival times and survival curves, there were no statistically significant differences among the various treatment subgroups. A comparison of survival curves revealed the interesting finding that the PAP-related response showed a clear correlation to the survival curves of Group 2 patients.

Topics: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Diethylstilbestrol; Doxorubicin; Estramustine; Fluorouracil; Humans; Male; Middle Aged; Neoplasm Staging; Nitrogen Mustard Compounds; Peplomycin; Prospective Studies; Prostatic Neoplasms; Random Allocation

The influence on the specific cell-mediated immunity (CMI) of the carcinoma of the prostate gland by the contra-sexual hormone therapy with Cytonal, Estrazyt and Turisteron is controlled. For this purpose the macrophage-electrophoresis-mobility test on the basis of allogenic tumour-associated antigen of the carcinoma of the prostate gland is used. As a result the use of Cytonal at least in the dosage hitherto used is no longer worth being advocated. Turisteron and Estrazyt, respectively, taking into consideration their pharmacokinetics and indication, prove to be immunologically optimal and without hesitation, respectively. Turisteron is the basic therapeutic in the androgen-dependent carcinoma of the prostate gland. Estrazyt should be reserved to primarily and secondarily hormone-refractory tumours. For the application of Estrazyt an additive immune stimulation seems to be worth taking into consideration.

Topics: Aged; Antineoplastic Agents; Clinical Trials as Topic; Combined Modality Therapy; Diethylstilbestrol; Estramustine; Ethinyl Estradiol; Humans; Immunity, Cellular; Macrophages; Male; Middle Aged; Nitrogen Mustard Compounds; Prostatic Neoplasms; Random Allocation

Efficacy of orchiectomy and intravenous administration of diethylstilbestrol diphosphate (DESP) for the treatment of prostatic carcinoma was evaluated on 184 patients treated between 1975 to 1989. The patients were between 49 to 88 years old with a mean age of 73.4 +/- 8.3 years. Clinical stage was A in 9.8%, B in 12%, C in 26.6% and D in 51.6%. The histologically well, moderately and poorly differentiated adenocarcinoma were observed in 20.9, 29.4 and 49.7%, respectively. The 5-year survival rate of stage A, B, C and D calculated with the Kaplan-Meier method were 90, 49, 60 and 34%, respectively. The 5- and 10-year survival rate of the patients who had received orchiectomy was 53 and 24%, respectively, while that of the patients without orchiectomy was 38 and 14%, respectively. The 5 and 7-year survival rate of the patients treated with intravenous administration of DESP was 54 and 34%, respectively while that of the patients without DESP was 46 and 31%, respectively. These findings suggest that orchiectomy and intravenous administration of DESP in any form prolonged patient survival compared with only oral administration of estrogens or antiandrogens. Reactivation was seen in 24 (40%) of the 60 patients under sufficient observation. Clinical relapse occurred within an average of 32.3 +/- 26.4 months after primary hormonal manipulation. The average time to relapse in stage D was shorter than that in stage B and C. Reactivation was observed in the patients on interrupted treatment earlier than in the patients on continuous administration of drugs. Cardiovascular death followed by endocrine therapy was 7.4% in this study.

Topics: Adenocarcinoma; Administration, Oral; Aged; Aged, 80 and over; Antineoplastic Agents; Chlormadinone Acetate; Combined Modality Therapy; Diethylstilbestrol; Drug Administration Schedule; Estramustine; Humans; Injections, Intravenous; Male; Middle Aged; Neoplasm Staging; Orchiectomy; 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

Chemilumenescence (CL) occurs due to the phagocytosis of bacteria and of tumor cells by polymorphonuclear neutrophils (PMN). Levels of CL were measured in patients with prostatic cancer and from normal subjects. Patients with advanced disease (stage C, D) showed no elevated CL levels as compared to healthy individuals or patients with minimal disease (stage A, B). Following external radiation therapy in patients with stage A-C prostatic carcinoma high levels of CL were recorded. Estrogen medication also resulted in increased CL levels, while estramustine did not affect phagocytic activity. Intradermal BCG vaccination caused increased PMN activity. Progressive prostatic cancer in hormone treated patients was associated with increased CL as compared to patients with stable or regressive disease.

Topics: Antineoplastic Agents; BCG Vaccine; Diethylstilbestrol; Estramustine; Granulocytes; Humans; Luminescent Measurements; Male; Phagocytosis; Prostatic Neoplasms

23 patients with prostatic cancer were treated with (Estracyt) estramustine phosphate disodium, (Hexron) hexestrol, and (Honvah) diethylstilbestrol 4, 4-diphosphoric ester. 16 cases were given 560-840 mg of Estracyt, 6 cases 30 mg of Hexron, and 1 case 200 mg of Honvan orally daily. Fasting serum lipids and lipoproteins fractions were measured before and during this treatment with these drugs. The results were as follows. 1) In the 1-2 months of Estracyt administration a decrease of (TC) total cholesterol and extreme increase of (TG) triglycerides were confirmed. 2) In those 5 cases where 840 mg of Estracyt/day was given, almost no difference was observed in their TC, (NEFA) free fatty acids, or (PL) phospholipid values. 3) Cardiovascular complications although not serious, were found in 2 cases of the group receiving Estracyt. With these 2 cases, their beta+pre-beta/alpha lipoprotein fraction ratio decline was either very gradual or rather turned to increase markedly despite the extreme rise of their TG values. 4) The serum lipid values in the group receiving Hexron did not show any obvious changes in TG. These values did not change much in the first 5-6 months but an increase was seen between 7-9 months. Lipoprotein fractions were similar to those in the Estracyt group. 5) With those receiving Honvan, TG values began to rise 2-4 weeks following administration. In view of the above results, the coronary risk factors which are a consequence of Estracyt, Honvan, or Hexron ingestion for treatment of prostatic cancer must be taken very seriously and must be closely monitored. (Authors' modified)

Topics: Aged; Diethylstilbestrol; Estramustine; Hexestrol; Humans; Lipids; Lipoproteins; Male; Middle Aged; Nitrogen Mustard Compounds; Prostatic Hyperplasia; Prostatic Neoplasms