cyproterone and Adenocarcinoma

A case of orbital metastasis from Whitmore stage D adenocarcinoma of the prostate is described. Clinically, it presented as rapidly progressing exophthalmos of the right eye with elevation (ptosis) and abduction paralysis. The associated clinical picture of a one-year history of prostatism prompted patient referral to our department. When a patient presents with an orbital tumor and a history of cancer localized to another site, the metastatic origin of the condition should be suspected and metastasis to other sites sought. A negative finding warrants performing orbital biopsy to confirm the diagnosis. Although excision of single metastatic tumors in this site has been described, coexisting metastasis to bone and lymph nodes, the hormone dependence that these present and prostatic cancer contraindicate resection of the orbital metastatic tumor. Following bilateral orchiectomy and hormone therapy with antiandrogens micturitional symptomatology improved, tumor size was reduced, and exophthalmos disappeared. The case described herein is not the first case of this type of metastatic lesion reported in the literature; 28 cases have been reported to date. This uncommon clinical presentation with extraurological manifestations gives us an idea of the broad clinical spectrum the biological behaviour of this tumor type can adopt.

Topics: Adenocarcinoma; Aged; Antineoplastic Agents; Cyproterone; Cyproterone Acetate; Exophthalmos; Humans; Male; Orbital Neoplasms; Orchiectomy; Palliative Care; Prostatic Neoplasms

Topics: Adenocarcinoma; Age Factors; Aged; Cyclophosphamide; Cyproterone; Diethylstilbestrol; Fluorouracil; Humans; Male; Neoplasm Metastasis; Nitrogen Mustard Compounds; Prognosis; Prostatectomy; Prostatic Hyperplasia; Prostatic Neoplasms; Urination

Topics: Adenocarcinoma; Biopsy; Cyproterone; Diethylstilbestrol; Estrogens; Humans; Hypophysectomy; Lymphatic Metastasis; Male; Neoplasm Metastasis; Prostate; Prostatic Neoplasms

Radical radiotherapy is a standard form of management of localised prostate cancer. Conformal treatment planning spares adjacent normal tissues reducing treatment-related side effects and may permit safe dose escalation. We have tested the effects on tumour control and side effects of escalating radiotherapy dose and investigated the appropriate target volume margin. After an initial 3-6 month period of androgen suppression, 126 men were randomised and treated with radiotherapy using a 2 by 2 factorial trial design. The initial radiotherapy tumour target volume included the prostate and base of seminal vesicles (SV) or complete SV depending on SV involvement risk. Treatments were randomised to deliver a dose of 64 Gy with either a 1.0 or 1.5 cm margin around the tumour volume (1.0 and 1.5 cm margin groups) and also to treat either with or without a 10 Gy boost to the prostate alone with no additional margin (64 and 74 Gy groups). Tumour control was monitored by prostate-specific antigen (PSA) testing and clinical examination with additional tests as appropriate. Acute and late side effects of treatment were measured using the Radiation Treatment and Oncology Groups (RTOG) and LENT SOM systems. The results showed that freedom from PSA failure was higher in the 74 Gy group compared to the 64 Gy group, but this did not reach conventional levels of statistical significance with 5-year actuarial control rates of 71% (95% CI 58-81%) in the 74 Gy group vs 59% (95% CI 45-70%) in the 64 Gy group. There were 23 failures in the 74 Gy group and 33 in the 64 Gy group (Hazard ratio 0.64, 95% CI 0.38-1.10, P=0.10). No difference in disease control was seen between the 1.0 and 1.5 cm margin groups (5-year actuarial control rates 67%, 95% CI 53-77% vs 63%, 95% CI 50-74%) with 28 events in each group (Hazard ratio 0.97, 95% CI 0.50-1.86, P=0.94). Acute side effects were generally mild and 18 weeks after treatment, only four and five of the 126 men had persistent > or =Grade 1 bowel or bladder side effects, respectively. Statistically significant increases in acute bladder side effects were seen after treatment in the men receiving 74 Gy (P=0.006), and increases in both acute bowel side effects during treatment (P=0.05) and acute bladder sequelae (P=0.002) were recorded for men in the 1.5 cm margin group. While statistically significant, these differences were of short duration and of doubtful clinical importance. Late bowel side effects (RTOG> or =2) were seen more commonl

Topics: Adenocarcinoma; Aged; Androgen Antagonists; Cyproterone; Humans; Male; Maximum Tolerated Dose; Middle Aged; Neoadjuvant Therapy; Pilot Projects; Prostate-Specific Antigen; Prostatic Neoplasms; Radiation Injuries; Radiotherapy Dosage; Radiotherapy, Conformal; Rectum; Treatment Outcome; Urinary Bladder

During a 2-year period, 37 patients with symptomatic metastatic prostatic cancer were included in a prospective randomized phase-III trial. Nineteen patients were randomized to subcapsular orchiectomy, and 18 to cyproterone acetate (CPA) treatment with a dose of 50 mg b.i.d. The median age of the patients was 74 years (range 48-88 years), with no differences between the treatment groups. At 3, 6, and 12 months after initiation of the therapy and then every 6 months, patients were clinically and biochemically examined, and isotope scans and X-rays were performed. All patients were followed until death. Relief from symptoms was found following 3 months of treatment in 70.6% (95% confidence limits = 44.0-89.7%) of the patients treated with CPA, and in 83.3% (95% confidence limits = 58.6-96.4%) of the orchiectomized patients. The median time to relapse was 9 months in the CPA group, and 11 months in the orchiectomy group (p greater than 0.05). The median survival time was 13 months, with no differences between the groups. The treatment of advanced prostatic cancer with CPA is found to be a valuable alternative to orchiectomy.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Antineoplastic Agents; Bone Neoplasms; Cyproterone; Cyproterone Acetate; Humans; Male; Middle Aged; Orchiectomy; Palliative Care; Prospective Studies; Prostatic Neoplasms

In a prospective controlled clinical trial, 108 patients with pancreatic adenocarcinoma were randomly allocated to receive tamoxifen 20 mg b.d., cyproteron acetate 100 mg t.d.s. or no active treatment. The median survival of those receiving tamoxifen was longer than either of the other two groups (5.25 compared to 4.25 and 3 months, respectively) but this difference did not achieve statistical significance. Cox regression analysis of 12 clinical and biochemical features showed that, for the entire group of patients, survival was significantly longer in younger patients, those undergoing surgical bypass and those with better initial performance status. However, even when adjustment was made to allow for the distribution of these prognostic variables within the three groups, the difference in survival still did not achieve statistical significance. No side-effects attributable to treatment was observed.

Topics: Adenocarcinoma; Aged; Androgen Antagonists; Antineoplastic Agents; Cyproterone; Cyproterone Acetate; Female; Humans; Male; Middle Aged; Pancreatic Neoplasms; Prospective Studies; Tamoxifen

Topics: Adenocarcinoma; Clinical Protocols; Clinical Trials as Topic; Cyproterone; Cyproterone Acetate; Diethylstilbestrol; Europe; Humans; Male; Orchiectomy; Prostatic Neoplasms

Thirty-four previously untreated patients with advanced prostatic carcinoma, histologically graded as being of intermediate differentiation, were randomized in three groups. All patients were treated with primary orchiectomy, group I was observed without additional therapy, group II treated with oral administration of prednisone and group III treated with cyproterone acetate per os. The clinical results with the combination orchiectomy and prednisone was encouraging both when initial and secondary remissions were considered. Cyproterone acetate treatment induced a highly significant raise in plasma prolactin, a fact which may explain the less favourable clinical results in this group.

Topics: Adenocarcinoma; Aged; Castration; Clinical Trials as Topic; Cyproterone; Cyproterone Acetate; Humans; Male; Prednisone; Prostatic Neoplasms; Random Allocation

Forty-two patients with previously untreated T3/4 N1-4 MO/1 prostatic adenocarcinoma were treated with either cyproterone acetate (n = 21; 300 mg intramuscularly per week) or oestradiol undecylate (n = 21; 100 mg intramuscularly per month) after extensive staging which included open skeletal biopsy and pelvic lymphadenectomy in some cases. Subjective and objective parameters as well as signs of drug toxicity were recorded regularly. Evaluation after 6 months showed cyproterone acetate to be more effective in the following respects: (1) the significantly different castration effect as judged by plasma testosterone, (2) the objective voiding pattern and tumour response, with regression of palpable and histologically evaluable local tumour in 16 of 21 patients, and (3) side effects and untoward reactions. Thus cyproterone acetate is suggested as a valuable alternative in the treatment of advanced prostatic cancer.

Topics: Adenocarcinoma; Aged; Clinical Trials as Topic; Cyproterone; Estradiol; Humans; Male; Middle Aged; Prostatic Neoplasms; Random Allocation; Time Factors

Since prolactin has several modes of action on prostatic growth and physiology, the effect of the antiprolactin bromocriptine on plasma kinetics and intraprostatic metabolism of testosterone was studied in patients with untreated prostatic cancer; a therapy protocol was deduced which was controlled in 27 patients with advanced inoperable prostatic adenocarcinoma. Bromocriptine resulted in a significant suppression of prolactin and testosterone as well and favored testosterone elimination from the plasma pool. Prostatic androgen uptake was enhanced and the intraprostatic metabolism altered in relation to tumor grade. Adjunctive administration of bromocriptine to 27 patients, mostly in the state of hormone resistance, resulted in an overall objective regression of 22.2% and in stable disease in 55.6% of the patients. In half of the individuals a prompt relief of bone pain from osseous metastases was observed as well as improvement of micturition and decline of phosphatase activity. This preliminary data justify further investigations under controlled and randomized conditions.

Topics: Adenocarcinoma; Aged; Androgens; Bromocriptine; Clinical Trials as Topic; Cyproterone; Humans; Male; Middle Aged; Palliative Care; Prolactin; Prostate; Prostatic Neoplasms; Testosterone

Prostate carcinoma is one of the most frecuent cancers in men. Significant numbers of patients have regional lymph node and bone metastases during the course of the disease. Mediastinal lymphadenopathy and cutaneous metastases are uncommon and signify well-advanced disease. We report the case of a patient with prostate cancer who develops mediastinal lymphadenopathy, pulmonary nodules and cutaneous metastases 8 years after the diagnosis.

Topics: Adenocarcinoma; Androgen Antagonists; Androgens; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Cyproterone; Diphosphonates; Estramustine; Fatal Outcome; Flutamide; Humans; Imidazoles; Ketoconazole; Lung Neoplasms; Lymphatic Metastasis; Male; Mediastinum; Neoplasms, Hormone-Dependent; Prostatic Neoplasms; Radionuclide Imaging; Skin Neoplasms; Triptorelin Pamoate; Zoledronic Acid

Late chronic side effects of the rectum constitute one of the principal limiting factors for curative radiation therapy in patients with prostate cancer. The purpose of the study was to determine the impact of immediate androgen deprivation (IAD) prior to conformal radiotherapy on rectal volume exposed to high doses, as compared with a deferred treatment strategy (DAD). Twenty-five patients (13 in the IAD group and 12 in the DAD group) with bulky tumours of the prostate, T3pN1-2M0 from the prospective EORTC trial 30846 were analysed. Three-dimensional conformal radiation treatment plans (3DCRT) using a 4-field box technique were generated based on the digitized computed tomographic or magnetic resonance findings acquired during the first 9 months after inclusion in the EORTC trial. Dose-volume histograms (DVHs) were calculated for the prostate and rectum. In the DAD group, there was no obvious alteration in the mean size of the prostate or other evaluated structures. In the IAD patients, a statistically significant reduction of approximately 40% of the gross tumour volume (GTV) was reached after a 6 months' course of hormonal treatment (p < 0.001). High-dose rectal volume was correlated with the volume changes of the GTV (p < 0.001). Mean rectal volume receiving 95% or more of the target dose was significantly reduced by 20%. Our study confirms the effect of downsizing of locally advanced prostate tumours following AD treatment and demonstrates the interdependence of the high-dose rectal volume with the volume changes of the GTV. However, the mean beneficial sparing of rectal volume was outweighed in some patients by considerable inter-patient variations.

Topics: Adenocarcinoma; Androgen Antagonists; Antineoplastic Agents, Hormonal; Chemotherapy, Adjuvant; Combined Modality Therapy; Cyproterone; Gonadotropin-Releasing Hormone; Goserelin; Humans; Male; Prostatic Neoplasms; Radiotherapy Dosage; Radiotherapy, Conformal; Rectum

Relapsing polychondritis is a chronic rheumatologic disorder of unknown etiology. Cutaneous manifestations occur in nearly half of the patients and often precede cartilaginous involvement. We present the case of a man with a history of prostatic adenocarcinoma who underwent monthly injections of goserelin (Zoladex), an LH-RH analogue. Five months after the beginning of the treatment, he presented cutaneous manifestations, which then recurred monthly, after each goserelin injection. After goserelin interruption and replacement with another treatment (cyproterone acetate), the patient was asymptomatic for 2 months. A cutaneous relapse then occurred followed by a typical cartilaginous involvement. In our observation, goserelin seems to have triggered the cutaneous manifestations of relapsing polychondritis. An hormonal precipitating factor in relapsing polychondritis has already been suggested by reports of patients whose disease worsened under chorionic gonadotropin treatment or during pregnancy.

Topics: Adenocarcinoma; Aged; Androgen Antagonists; Antineoplastic Agents, Hormonal; Cartilage Diseases; Cyproterone; Drug Eruptions; Erythema; Gonadotropin-Releasing Hormone; Goserelin; Humans; Male; Polychondritis, Relapsing; Prostatic Neoplasms; Purpura; Recurrence

A fall in the PSA level after stopping antiandrogens has been described at the stage of hormonal escape of prostatic cancer treated by complete androgen inhibition. The authors report a new case. The patient was offtially treated by pulpectomy and nitulamide for N+ prostatic carcinoma (PSA: 165 ng/ml). At the stage of hormonal escape, discontinuation of nitulamide induced a reduction of the PSA. Replacement of nitulamide by cytoproterone acetate was followed by a renewed increase of PSA, which again decreased after stomming cyproterone acetate. Three years later, the PSDA level was 3.5 ng/mg. This syndrome is probably due to mutation of the androgen receptor. In hormonal escape, suspension of all antiandrogens apart from LHRH analogues is recommended and can be followed by a temporary fall of PSA. No other antiandrogen must be administered in the place of the previous drug.

Topics: Adenocarcinoma; Aged; Androgen Antagonists; Antineoplastic Agents, Hormonal; Chemotherapy, Adjuvant; Cyproterone; Humans; Imidazoles; Imidazolidines; Lymphatic Metastasis; Male; Prostate-Specific Antigen; Prostatectomy; Prostatic Neoplasms; Substance Withdrawal Syndrome

The presentation of prostatic carcinoma with pulmonary metastases is unusual. The patient reported here presented with nodular lung metastases from an unknown primary site and 3.5 years later became symptomatic with a prostatic carcinoma. Subsequent hormonal therapy led to radiological regression of the pulmonary metastases. This case report demonstrates the progression of asymptomatic prostatic lung metastases with time and their response to delayed hormonal therapy, which is discussed.

Topics: Adenocarcinoma; Aged; Androgen Antagonists; Antineoplastic Agents, Hormonal; Cyproterone; Follow-Up Studies; Humans; Lung Neoplasms; Male; Neoplasms, Unknown Primary; Prostatic Neoplasms; Remission Induction

A case of stenosis of the rectum, a very rare complication of prostate cancer, is reported. One year after operation for an authentic histologically confirmed adenoma of the prostate gland, the patient progressively developed stenosis of the rectum. The prostatic origin of the stenosis was rapidly established after dilatation of the rectum and histological examination of the transrectal biopsy. Therapeutic attitudes vary according to the circumstances. Severe stenosis could lead to occlusion or subocclusion requiring temporary colostomy. Rectal dilatations have been proposed. This method was used in this case during the critical stage and to allow transrectal biopsy. Hormone therapy is the basic treatment. This pathology is extremely rare with a frequency of 2% according to certain authors and 1% in the series reported here.

Topics: Adenocarcinoma; Aged; Antineoplastic Agents; Barium Sulfate; Cyproterone; Cyproterone Acetate; Enema; Humans; Male; Prostatic Neoplasms; Radiography; Rectal Diseases; Rectum

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Antineoplastic Agents; Chemical and Drug Induced Liver Injury; Cyproterone; Cyproterone Acetate; Humans; Male; Prostatic Neoplasms

On the basis of a retrospective series of 74 patients with adenocarcinoma of the prostate, the authors study the survival of these patients according to the clinical stage of the lesion when treated with cyproterone acetate. Biologically speaking, the authors have studied the evolution of the blood testosterone level, as well as of PSA and PAPs. Their conclusion is that the PSA is an excellent indicator of the efficacy of the cyproterone acetate treatment. Its fast decrease proves treatment efficacy, while a new rise indicates the resumption of evolution of the neoplastic process and must lead to change the therapeutic approach.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Antigens, Neoplasm; Cyproterone; Cyproterone Acetate; Follow-Up Studies; Humans; Male; Middle Aged; Prostate-Specific Antigen; Prostatic Neoplasms; Retrospective Studies; Testosterone

Groups of 20-25 male Wistar rats (Cpb:WU), nine groups of 4-week-old rats, and nine groups of 8-week-old rats, were given cyproterone acetate (CA) s.c. or by gavage daily for 18 days at a dose of 50 mg/kg/day. Directly following CA treatment, the rats received 3 daily s.c. injections with testosterone propionate (TP) at a dose of 100 mg/kg/day. On the day after the last TP administration, a single dose of one of the following carcinogens was given to 3 groups: N-methyl-N-nitrosourea (MNU), 50 mg/kg i.v.; 7,12-dimethylbenz(a)anthracene, 30 mg/kg i.v.; 3,2'-dimethyl-4-aminobiphenyl, 250 mg/kg s.c. Three other groups received the same carcinogen treatments after 7 days of recovery from the CA administration. The last 3 groups received carcinogen without TP treatment, but immediately after CA pretreatment was stopped. A 25% incidence of invasively growing, metastasizing adenocarcinomas was found in the dorsolateral prostate region of 8-week-old rats that had received MNU after treatment with CA plus TP. In addition, this group had a 5% incidence of carcinoma in situ and a 5% incidence of atypical hyperplasia in the dorsolateral prostate. Lower incidences of adenocarcinoma of the dorsolateral prostate region and of carcinoma in situ and atypical hyperplasia of the dorsolateral prostate were found in other groups that were treated with MNU or 7,12-dimethylbenz(a)anthracene after pretreatment with CA, followed by TP or recovery, but never in rats that had been treated with CA only. In the groups treated with 3,2'-dimethyl-4-aminobiphenyl, which is slowly metabolized, these lesions were also found in groups that were pretreated with only CA. The carcinomas seemed to originate from the dorsolateral prostate and their average latency time was approximately 61 weeks. The 8-week-old rat given a MNU injection after sequential treatment with CA and TP may provide a relevant animal model for human prostatic cancer.

Topics: 9,10-Dimethyl-1,2-benzanthracene; Adenocarcinoma; Aminobiphenyl Compounds; Animals; Body Weight; Cyproterone; Cyproterone Acetate; Genitalia, Male; Male; Methylnitrosourea; Prostatic Neoplasms; Rats; Rats, Inbred Strains; Sarcoma, Experimental; Survival Analysis; Testosterone

Epidemiological and experimental studies suggest that androgens influence colonic carcinogenesis. We investigated the effects of hormonal manipulations (surgical and chemical castration, hormone substitution) on colonic tumour development, tumour and mucosal histopathology, and epithelial proliferation in macroscopically normal colonic mucosa in male rats, after induction of chemical colon carcinogenesis by subcutaneous injections of azoxymethane (AOM). Chemical castration with cyproterone acetate, but not surgical castration, resulted in increased colonic tumorigenesis, which was accompanied by decreased crypt length, decreased number of cells per crypt, and increased crypt epithelial mitotic index in the right colon. Chemically castrated rats also had crypt hyperplasia and increased numbers of dysplastic foci in the left colon which were not seen with surgical castration. By contrast, rats given testosterone after surgical castration showed decreased colonic tumorigenesis with an increased proportion of tumours in the left colon and lower percentage of tumours with invasion. The grossly normal mucosa of the testosterone-substituted castrated rats showed decreased crypt length in the right colon similar to the other groups of castrated rats, but no significant increase in mitotic index. Our results suggest that the anti-androgenic progestin cyproterone is a potent enhancer of colonic tumorigenesis and epithelial proliferative abnormalities after AOM administration. Exogenous testosterone after castration alters tumour distribution and characteristics and suppresses epithelial proliferative abnormalities. Finally, androgen effects on the colonic mucosa are more prominent in the right than in the left colon, suggesting different influences of hormones on the epithelium of these anatomical sites.

Topics: Adenocarcinoma; Animals; Azoxymethane; Colonic Neoplasms; Cyproterone; Cyproterone Acetate; Drug Synergism; Intestinal Mucosa; Male; Mitotic Index; Orchiectomy; Rats; Rats, Inbred Strains; Testosterone

A patient is described who presented with left upper lobe collapse due to endobronchial metastatic prostate carcinoma. Treatment with the oral antiandrogen cyproterone acetate resulted in resolution of the occluding endobronchial carcinoma and lobar re-expansion.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Androgen Antagonists; Cyproterone; Cyproterone Acetate; Humans; Lung; Lung Neoplasms; Male; Prostatic Neoplasms; Pulmonary Atelectasis

A case of severe acute hepatitis caused by cyproterone acetate in a 71 year old man with prostatic carcinoma is reported with a review of the literature on hepatic reactions to this drug. The association between the use of cyproterone acetate and liver abnormalities is poorly documented. This is the fourth published report of adverse hepatic reaction to cyproterone acetate and it substantiates other evidence that cyproterone acetate is potentially hepatotoxic. Monitoring of liver function tests should be mandatory in patients receiving high doses of cyproterone acetate; the drug should be withdrawn immediately if abnormal liver function tests are found.

Topics: Adenocarcinoma; Aged; Aspartate Aminotransferases; Bilirubin; Chemical and Drug Induced Liver Injury; Cyproterone; Cyproterone Acetate; Humans; Liver; Male; Prostatic Neoplasms

Regarding a case of little-differentiated adenocarcinoma of prostate in a 79-year old male patient undergoing antiandrogenic corticosteroid therapy (cyproterone acetate), the authors describe a rare complication related to treatment with the drug. Cytolytic icterus, without cholestasis, occurred eleven weeks after starting the treatment without metastasis of the primary cancerous lesion, and regressed when administration of the antiandrogenic agent was interrupted. This description is compatible with toxic hepatitis. This is a rare complication, which should be differentiated from stasis icterus consecutive to treatment with progestogens. Its diagnosis precludes also primary or drug-induced secondary tumors or degenerative hepatic lesions. A knowledge of this complication by the urologist is important, so the latter might not conclude too hastily to metastatic extension of primary cancer of prostate. Withdrawal of the patient from antiandrogenic therapy is mandatory, and management should incorporate complete biological investigation of liver function, CT scans and, depending upon the case, liver biopsy as the only means of studying this exceptionally rare complication.

Topics: Adenocarcinoma; Aged; Chemical and Drug Induced Liver Injury; Cyproterone; Cyproterone Acetate; Humans; Male; Prostatic Neoplasms

Topics: Adenocarcinoma; Adult; Breast Neoplasms; Buserelin; Combined Modality Therapy; Cyproterone; Cyproterone Acetate; Femoral Neoplasms; Gonadotropin-Releasing Hormone; Humans; Injections, Subcutaneous; Male; Tamoxifen; Triptorelin Pamoate

Topics: Adenocarcinoma; Aged; Androgen Antagonists; Busulfan; Cyproterone; Cyproterone Acetate; Humans; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Male; Neoplasms, Multiple Primary; Prostatic Neoplasms; Remission Induction

The transplantable human prostatic adenocarcinoma, PC-82, has been shown to be a suitable model for the study of several aspects of androgen-regulated tumor growth. This tumor contains an androgen receptor, and the purpose of the present investigation was to characterize this androgen receptor with respect to hormone specificity, sedimentation coefficient, dissociation constant, Stokes radius, ionic properties, and molecular mass. Cytosol was prepared from tumor tissues grown in athymic nude mice, which were castrated 10 days before harvesting the tumor. Scatchard plot analysis revealed a binding protein with a Kd of 0.1 nM for R1881 (methyltrienolone) and binding capacity of 120 fmol/mg protein. The receptor showed a high affinity for R1881, testosterone, and 5 alpha-dihydrotestosterone, respectively, whereas no or little affinity was found for progesterone and estradiol. In the presence of 10 mM molybdate the androgen receptor in PC-82 cytosol eluted from an FPLC anion exchange column (Mono Q) at 0.32 M NaCl, which is identical to what has been found for androgen receptors from rat prostate and calf uterine cytosol. Photoaffinity labeling of the [3H]R1881-androgen receptor complex and subsequent analysis on SDS-polyacrylamide gels resulted in a covalently labeled protein with a molecular mass of approximately 50 kD. The androgen receptor of the PC-82 tumor had a sedimentation coefficient of 4S and a Stokes radius of 3.3 nm at high ionic strength (0.4 M NaCl). It is concluded that the PC-82 tumor contains a binding protein with the properties described for androgen receptors present in prostate tissue.

Topics: Adenocarcinoma; Cell Line; Cyproterone; Cyproterone Acetate; Dihydrotestosterone; Estradiol; Estrenes; Humans; Male; Metribolone; Molecular Weight; Neoplasm Transplantation; Progesterone; Prostatic Neoplasms; Receptors, Androgen; Testosterone; Triamcinolone Acetonide

Organ culture of the rat ventral prostate has been evaluated as a model for studying the biological effects of androgen agonists, androgen antagonists, and estrogens. Explants were cultured for up to 8 days, and incorporation of (3H)-thymidine and (3H)-uridine by the explants was measured. Dihydrotestosterone (DHT) increased the incorporation of (3H)-thymidine/microgram DNA when compared with the untreated controls at 4 days, P less than .05; and at 6 days, P less than .01. Enhanced uptake in explants from 6 to 8-week old rats also was observed with 10 nM estradiol (P less than .05) and 10 nM cyproterone acetate (P less than .02). DHT (10 nM) caused greater enhancement of uptake in explants from 3-week-old rats than in explants from 6- or 12-week-old rats. In contrast, estradiol (E2) increased incorporation only in prostates from the 6-week-old rats. Since both DHT and E2 can enhance (3H)-thymidine uptake even though they are associated with strikingly different effects on prostate morphology, it suggests that their effects on (3H)-thymidine incorporation are mediated by different cells.

Topics: Adenocarcinoma; Age Factors; Androgens; Animals; Cyproterone; Cyproterone Acetate; Estradiol; Estrogens; Insulin; Male; Mice; Organ Culture Techniques; Prostate; Prostatic Neoplasms; Rats; Rats, Inbred Strains; Testosterone

Of 749 patients with carcinoma of the prostate 133 (17.8%) presented with total urinary retention; 122 of the 133 patients were given different forms of endocrine therapy. Only 8 patients were treated by initial transurethral resection of the prostate, and 3 patients received no treatment. After endocrine therapy 80 (65.6%) of 122 patients were free from catheter six months after starting treatment. The response to orchidectomy appeared earlier than that to treatment with estrogens. The mean period of catheterization for the 80 patients who responded was 2.7 months after orchidectomy and 3.4 months during estrogen treatment. The difference was statistically significant (p less than 0.05).

Topics: Adenocarcinoma; Aged; Castration; Cyproterone; Cyproterone Acetate; Drug Therapy, Combination; Estradiol; Estradiol Congeners; Estrogens; Ethinyl Estradiol; Humans; Male; Middle Aged; Prostatic Neoplasms; Urethral Obstruction

Standard initial therapy for metastatic prostatic cancer involves surgical or chemically induced castration. Castration lowers the serum testosterone level by over 90% but does not completely eliminate all potential serum androgens (i.e., it induces a partial androgen withdrawal). This has led some investigators to suggest that a more complete form of androgen withdrawal in which the very low levels of serum androgens remaining after castration are neutralized by the simultaneous treatment with a direct acting antiandrogen (i.e., complete androgen withdrawal) might be more effective than simply castration alone. To determine whether complete androgen withdrawal is any more effective than partial androgen withdrawal therapy, the slow growing, well differentiated H and the fast growing, poorly differentiated G sublines of the serially transplantable Dunning R-3327 system of rat prostatic adenocarcinomas were used as a test system since both of these cancers are androgen responsive. These studies demonstrated that: (a) complete androgen withdrawal consisting of surgical castration in combination with daily treatment with the potent antiandrogen, cyproterone acetate, was no more effective in terms of tumor growth retardation or overall host survival than was partial androgen withdrawal induced by castration alone; (b) serum testosterone levels must be maintained below 0.5 ng/ml but do not have to be completely eliminated to produce the maximum therapeutic response; and (c) prostatic cancers are more sensitive than is the normal prostate to growth stimulation by serum testosterone.

Topics: Adenocarcinoma; Animals; Cell Division; Cyproterone; Dihydrotestosterone; Laminin; Male; Microscopy, Electron; Neoplasm Transplantation; Ovariectomy; Prostatic Neoplasms; Rats; Testosterone

Serum concentrations of gonadotropins, testosterone and dehydrotestosterone were determined in patients receiving conventional endocrine therapy for advanced metastatic adenocarcinoma of prostate. The effect over 4 h of a single dose of a long acting analogue of LHRH was determined in these patients and compared to the response in patients receiving the analogues as first choice of treatment. Oestrogen therapy was found to suppress basal and stimulated gonadotropins and testicular androgens. Cyproterone therapy only partially reduced basal hormone concentrations and the response to the LHRH analogue was delayed. Orchidectomy resulted in elevated gonadotropins and an exaggerated response to the analogue. As patients who relapse while failing conventional therapy, may subsequently be treated by further endocrine manipulation, precise determination of their endocrine status should predict any expected benefit. Patients previously treated with stilboestrol are unlikely to respond to orchidectomy or LHRH analogue.

Topics: Adenocarcinoma; Buserelin; Castration; Cyproterone; Cyproterone Acetate; Diethylstilbestrol; Follicle Stimulating Hormone; Goserelin; Humans; Luteinizing Hormone; Male; Prostatic Neoplasms; Testosterone

Topics: Adenocarcinoma; Aged; Brachytherapy; Cesium Radioisotopes; Cyproterone; Cyproterone Acetate; Estrogens; Gonadotropin-Releasing Hormone; Humans; Iridium; Lymph Node Excision; Male; Middle Aged; Orchiectomy; Prostatectomy; Prostatic Neoplasms; Triptorelin Pamoate

Prostatic adenocarcinomas were induced in 5 out of 20 Wistar rats upon a single administration of 50 mg/kg N-nitroso-N-methylurea (NMU). The rats were pretreated with a daily dose of 50 mg/kg cyproterone acetate for 3 weeks followed by 3 daily injections of 100 mg/kg testosterone. All tumours developed in the dorsolateral prostate and were invasively growing. In 2 cases distant metastases were found. Three proliferative lesions classified as carcinomas in situ were also found in the dorsolateral prostate. A total of 7/20 animals (35%) carried an adenocarcinoma and/or a carcinoma in situ. In addition, 6 epithelial hyperplasias were observed in the dorsolateral and 1 in the ventral prostate of non-tumour-bearing rats. The method described may provide a good animal model for cancer of the prostate and lead to a better understanding of prostatic carcinogenesis.

Topics: Adenocarcinoma; Animals; Carcinoma in Situ; Cocarcinogenesis; Cyproterone; Cyproterone Acetate; Male; Methylnitrosourea; Models, Biological; Neoplasm Metastasis; Neoplasms, Experimental; Nitrosourea Compounds; Prostatic Neoplasms; Rats; Rats, Inbred Strains; Testosterone

The present study has compared the response to antiandrogen therapy of the serially transplantable Dunning R-3327-AT (hereafter called AT) versus Dunning R-3327-G (hereafter called G) rat prostatic adenocarcinoma. Castration or chemical antiandrogen therapy (i.e., cyproterone acetate and diethylstilbestrol) of rats bearing established AT or G tumors results in neither regression of tumor volume nor a cessation of the continuous growth of either tumor. By these criteria, both the AT and G tumors progress following antiandrogen therapy. For the AT tumor, this progression is completely unresponsive to hormonal therapy, and thus such therapy does not increase survival of AT tumor-bearing rats. The AT tumor is therefore an example of hormonally unresponsive progression. In direct contrast, while the G tumor likewise progresses following antiandrogen therapy, this therapy does induce a 1.8-fold decrease in the subsequent growth rate of the G tumor. This positive response during progression of the G tumor results in a 78% increase in the survival of G tumor-bearing rats treated with antiandrogen therapy. The G tumor is therefore an example of hormonally responsive progression. These results indicate neither that prostatic cancers which do not regress or cease growing following antiandrogen therapy can necessarily be considered hormonally unresponsive nor that antiandrogen therapy of such tumors has been completely ineffective, since, as shown in the present study, such progression can be of either a hormonally unresponsive or a responsive type. Regardless of which type of progression occurs, however, additional therapy is required to further increase survival. The present study demonstrates that such additional therapy should probably not include the subsequent use of pharmacological doses of exogenous androgen, since, depending on the type of progression, such treatments can actually decrease survival.

Topics: Adenocarcinoma; Animals; Castration; Cell Division; Cyproterone; Cyproterone Acetate; Diethylstilbestrol; Kinetics; Male; Neoplasms, Experimental; Prostatic Neoplasms; Rats

Topics: Adenocarcinoma; Aminoglutethimide; Animals; Cyproterone; Hormones; Humans; Hydrocortisone; Male; Mice; Mice, Nude; Middle Aged; Neoplasm Transplantation; Neoplasms, Experimental; Pancreatic Neoplasms; Tamoxifen; Testosterone; Transplantation, Heterologous

An 80-year-old man with advanced adenocarcinoma of the prostate received cyproterone acetate, 200 mg orally per day as sole treatment. Striking regression of the tumour was demonstrated by ultrasonograms and excretory urograms. Serum concentrations of acid phosphatases, gonadotrophins, and testosterone decreased significantly. No significant cardiovascular side effects occurred.

Topics: Acid Phosphatase; Adenocarcinoma; Aged; Cyproterone; Humans; Male; Pituitary Hormones; Prostatic Neoplasms; Radiography; Testosterone

Topics: Adenocarcinoma; Bone Neoplasms; Cyproterone; Humans; Male; Middle Aged; Prostatic Neoplasms

Since prostatic carcionma is hormone dependent, treatment of this tumor has been carried out in this department over the last 10 years employing antiandrogens, particularly cyproterone acetate (CPA), associated in some cases with orchiectomy. Of 500 patients thus treated, the author reports on 236 patients with a 5-year follow-up and 184 with a 7-year follow-up. Of these, 126 (53.4%) had not received hormone treatment whereas 110 (46.6%) had been treated with estrogens. The mean survival rate was 64.4% at 5 years and 56.3% at 7 years in these patients and 51 and 43%, respectively, in the estrogen-treated patients. The author emphasizes that not only is CPA of great value in the treatment of prostatic carcinoma, but it is also useful in determining the hormone dependency of the tumor which is indispensable before proceeding with hormone therapy.

Topics: Adenocarcinoma; Castration; Cyproterone; Drug Evaluation; Follow-Up Studies; Humans; Male; Prostatic Neoplasms

Sixteen patients with prostatic carcinoma were treated with 200 mg of Cyproterone acetate daily. No other kind of hormonal treatment was given. Transrectal biopsies of the prostate were taken before the treatment was started, and at regular intervals afterwards. The treatment period lasted from 3 to 16 months, with an average of 9 months. A thorough examination of multiple sections from all specimens revealed no convincing signs of cellular involution. The study has demonstrated no specific or significant atrophic changes following Cyproterone acetate therapy. Some possible explanations regarding the effect of Cyproterone acetate on human malignant prostatic tissue are discussed.

Topics: Adenocarcinoma; Aged; Atrophy; Biopsy; Carcinoma; Cyproterone; Humans; Male; Middle Aged; Prostate; Prostatic Neoplasms

Topics: Adenocarcinoma; Antineoplastic Agents; Cyproterone; Drug Therapy, Combination; Endometriosis; Estrogens; Female; Humans; Kidney Neoplasms; Male; Prednisone; Progestins; Prostatic Neoplasms; Uterine Neoplasms