cyproterone and Neoplasm-Metastasis

The effectiveness of aminoglutethimide as an adrenal inhibitor has been well-documented by decreases in plasma testosterone and delta 4 levels, which fall significantly following the drug in previously orchiectomized patients. The use of cortisone or cortisol along with aminoglutethimide complicates the interpretation of the role of aminoglutethimide in effecting clinical responses. However, since physiologic replacement doses were used in most cases, a significant role for cortisone in effecting a clinical response is unlikely. Aminoglutethimide does have side-effects including rash and lethargy. It requires administration of replacement doses of cortisone and sometimes mineralocorticoid as well since it inhibits adrenal steroid synthesis in all pathways. Peripheral adrenal androgen inhibitors, such as flutamide, Megace, cyproterone acetate or 5 alpha-reductase inhibitors, in the future may be equally effective and simpler to administer than aminoglutethimide but objective and adequate numbers of studies using acceptable objective criteria must be done in order to adequately compare these drugs to aminoglutethimide. There appears to be approximately a 33% response rate (partial objective regression and objectively stable) following blockade of adrenal androgens in patients in relapse after castration. Blockade of adrenal androgen is certainly more tolerable and has many fewer side-effects than the alternative of chemotherapy which does not give response rates in most cases that are significantly different from those noted with aminoglutethimide. Murray's paper, combined with prior studies by Drago et al., goes a long way in establishing adrenal androgen blockade with that drug as the next step to be taken in patients following relapse from prior castration (medical or surgical). The most important question revolves around the timing of adrenal androgen blockade. As stated by Murray, will adrenal androgen blockade provide better survival if given earlier following relapse? The answer is not known yet. The answer may come from the work of Labrie [1], Geller and Albert [2] and others, who suggest that total survival in prostate cancer may be improved with blockade of adrenal androgens not after relapse following castration, but with panandrogen blockade at the time of initial therapy for prostate cancer.

Topics: Adrenalectomy; Aminoglutethimide; Androgen Antagonists; Castration; Combined Modality Therapy; Cyproterone; Cyproterone Acetate; Dehydroepiandrosterone; Dihydrotestosterone; Humans; Male; Megestrol; Megestrol Acetate; Neoplasm Metastasis; Prognosis; Prostate; Prostatic Neoplasms

Topics: Androgen Antagonists; Animals; Buserelin; Cyproterone; Cyproterone Acetate; Dogs; Drug Therapy, Combination; Flutamide; Humans; Male; Neoplasm Metastasis; Orchiectomy; Prostatic Neoplasms; Rats; Receptors, Cell Surface; Receptors, LHRH

Topics: Acid Phosphatase; Antineoplastic Agents; Bromocriptine; Castration; Combined Modality Therapy; Cyproterone; Estramustine; Estrogens; Fluorouracil; Humans; Lisuride; Male; Neoplasm Metastasis; Prostatic Neoplasms; Random Allocation

Postoperative adjuvant hormone therapy and hormone therapy in disseminated breast cancer will be discussed systematically. The classical ablative and additive endocrine therapeutic measures--with the exception of ovarectomy and gestagen therapy--are increasingly being replaced by antagonists. Individual chapters discuss recent experience with combined hormone-radiotherapy or hormone-chemotherapy. In addition, a successful therapy scheme for the treatment of disseminated breast cancer will be presented.

Topics: Adrenal Cortex Hormones; Adrenalectomy; Aminoglutethimide; Androgens; Breast Neoplasms; Castration; Cyproterone; Estrogens; Female; Gonadotropins; Hormones; Humans; Hydrocortisone; Hypophysectomy; Menopause; Neoplasm Metastasis; Progesterone; Tamoxifen

Topics: Biopsy; Castration; Cryosurgery; Cyproterone; Estrogens; Humans; Hypophysectomy; Male; Neoplasm Metastasis; Prostatic Neoplasms

Accurate diagnosis and staging of carcinoma of the prostate is essential to rational management of this disease. Once dissemination outside the periprostatic area is established, treatment is essentially limited to systemic efforts to control or suppress tumor growth and local efforts to minimize secondary effects of tumor deposits. Disseminated tumor limited to pelvic nodes constitute a possible exception to this statement since excisional and radiotherapeutic efforts to eradicate these foci may be successful. At the present time, changes in a number of objective and subjective parameters are utilized to assess the effect of therapeutic endeavors. When these are taken as a group and combined with a clinical judgement, they undoubtedly have merit. On the other hand, when utilized in a relative fashion as isolated indicators of tumor responsiveness or recurrence, their value is limited. Since most patients with disseminated carcinoma of the prostate die from their disease, critical analysis of survival data is at present likely to provide the most accurate assessment of a therapeutic endeavor. Estrogen administration or orchiectomy seem to be the systemic measures which combine relatively limited risk of morbidity with the greatest hope of initially controlling disseminated carcinoma of the prostate. Of these, evidence suggests that low dose estrogen therapy, 1 mg stilbestrol daily, provides the best opportunity for long-term control. Although length of survival does not seem to depend on the time at which the therapy is instituted, our prejudice is usually to start treatment when dissemination is recognized. The hope of providing a longer period of a better life by this practice requires evaluation. Combining local measures such as transurethral resection with systemic measures may add to patient comfort and longevity. Recurrent progression of tumor after initial hormonal measures in often difficult to recognize and accept. In patients with recurrent tumor activity, measures based on the concept of persistence of hormone dependence have produced disappointing results. More sophisticated selection techniques may identify a small group of patients in whom this approach is likely to produce desirable changes. For the most part chemotherapeutic agents hold greater promise of effective therapy in this group of patients.

Topics: Antineoplastic Agents; Body Fluids; Castration; Cyproterone; Diethylstilbestrol; Estrogens; Humans; Hypophysectomy; Immunotherapy; Male; Neoplasm Metastasis; Prostatectomy; Prostatic Neoplasms; Testosterone

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

Tumor flare is reported in up to 40% of patients treated with gonadotrophin-releasing hormone analogues for prostate cancer. In order to investigate the optimal way to eliminate tumor flare, we have treated patients with one of three different antiandrogen regimens used in combination with gonadotrophin-releasing hormone (GnRH) agonist. The early results of this study are presented here. Thirty patients with advanced symptomatic disease were randomized to receive either cyproterone acetate 50 or 100 mg three times daily or flutamide 250 mg three times daily given for 1 week before and during the first month of GnRH agonist treatment. The endocrine profiles of these patients were compared with those of historic controls treated with depot agonist alone. Three patients treated with low-dose cyproterone acetate and one with flutamide developed a transient exacerbation of their disease. No patients treated with the higher-dose cyproterone acetate regimen developed tumor flare. No patients treated with cyproterone acetate had an increase in serum testosterone above baseline following depot GnRH agonist implantation. All patients treated with flutamide had increases in serum testosterone, but this did not significantly increase further with implantation. This study suggests that all patients receiving GnRH agonist treatment should be pretreated with cyproterone acetate 100 mg three times daily for 1 week before implantation and for the first treatment month.

Topics: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Buserelin; Cyproterone; Cyproterone Acetate; Delayed-Action Preparations; Flutamide; Humans; Male; Middle Aged; Neoplasm Metastasis; Neoplasms, Hormone-Dependent; Phosphoric Monoester Hydrolases; Prostatic Neoplasms; Random Allocation; Testosterone

Topics: Clinical Trials as Topic; Combined Modality Therapy; Cyproterone; Cyproterone Acetate; Diethylstilbestrol; Humans; Male; Neoplasm Metastasis; Orchiectomy; Prostatic Neoplasms

Topics: Castration; Clinical Trials as Topic; Cyproterone; Diethylstilbestrol; Estramustine; Humans; Male; Medroxyprogesterone; Neoplasm Metastasis; Nitrogen Mustard Compounds; Prostatic Neoplasms; Random Allocation

Male breast cancer (MBC) is considered an androgen-dependent tumor, and as in prostatic cancer, responses have been reported with use of antiandrogens or gonadotropin-releasing hormone analogs. Thus, it is reasonable to postulate that better results could be achieved by combining these two agents.. Eleven men with recurrent or progressive carcinoma of the breast have been treated with buserelin 1500 micrograms subcutaneously daily in the first week and 600 micrograms daily subsequently and cyproterone acetate (CPA) 100 mg twice a day orally starting 24 hours before the first dose of buserelin.. Objective responses have been observed in seven patients with a median duration of 11.5 months (range, 9-24+ months). Responses were not correlated to the dominant site of disease. Three patients had stable disease lasting 5 months. Median survival was 18.5 months. Side effects primarily were decrease or loss of libido, impotence, and hot flushes.. Total androgen blockade with buserelin and CPA seems effective in the treatment of patients with advanced cancer of the male breast, but its superiority over standard androgen suppression remains to be demonstrated.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Buserelin; Cyproterone; Drug Administration Schedule; Humans; Male; Middle Aged; Neoplasm Metastasis; Treatment Outcome

Fifteen years ago we embarked on a treatment protocol for prostatic cancer patients with widespread disease (Stage D2) which included both hormonotherapy (i.e., orchiectomy and diethylstilbestrol [DES] 5 mg/day--later substituted with cyproterone acetate [CPA] 0.2 g/day) and chemotherapy (cyclophosphamide and 5-fluorouracil 10 mg/kg/week). The rationale for such an approach was the universally poor results obtained from the conventional approach which advocated consecutive single-treatment schedules once the previous therapy had ceased to be effective. As such a conventional approach probably allowed the selection of new resistant cell clones, we assumed that perhaps an aggressive combined systemic therapeutic approach from the start, would give such a group of patients--already with generalized disease--a better long-term result. In retrospect, after fifteen years, the chemotherapy on a series of 50 patients so treated has been well tolerated with only minimal, temporary side effects. This regimen was continued up to five years with a reduced maintenance dose. The hormonotherapy was also well tolerated, and was fully maintained. Only 28 percent died of their disease (16% within the first 2 years); 28 percent died of other causes; 40 percent are still alive (14% with clinical disease). In only 9 cases was the chemotherapy discontinued for various reasons. No control arm was originally designed in this protocol, but the long-term results suggest that our original concept was probably valid. Further studies, with the possible use also of newer chemotherapeutic agents, may well justify considering this combined therapeutic approach when dealing with this disease in its widespread form.

Topics: Aged; Aged, 80 and over; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Cyclophosphamide; Cyproterone; Cyproterone Acetate; Diethylstilbestrol; Fluorouracil; Follow-Up Studies; Humans; Male; Middle Aged; Neoplasm Metastasis; Orchiectomy; Prostatic Neoplasms; Retrospective Studies

In this paper the authors review the completed and current EORTC Genitourinary Group trials for metastatic carcinoma of the prostate. In terms of time to progression and length of survival, there is no significant difference between any of the effective endocrine treatments that have been studied. The statistical analysis of the different variables used in trials 30,761 and 30,762 determines three risk groups of patients. There is no need for very special laboratory investigations to establish a prognosis. Orchiectomy is the cheapest and safest endocrine treatment in metastatic carcinoma of the prostate.

Topics: Androgen Antagonists; Carcinoma; Cyproterone; Cyproterone Acetate; Diethylstilbestrol; Estramustine; Europe; Gonadotropin-Releasing Hormone; Hormones; Humans; Male; Medroxyprogesterone; Medroxyprogesterone Acetate; Neoplasm Metastasis; Neoplasms, Hormone-Dependent; Orchiectomy; Prostatic Neoplasms

Topics: Anilides; Combined Modality Therapy; Cyproterone; Flutamide; Gonadotropin-Releasing Hormone; Humans; Male; Megestrol; Neoplasm Metastasis; Orchiectomy; Prostatic Neoplasms; Receptors, Cell Surface; Receptors, LHRH

The hope of providing a safe alternative to bilateral orchiectomy for patients with prostatic cancer has spurred the development in recent years of various agents capable of reducing androgen level. Another reason for intensifying these efforts relates to the hope held by many clinicians that earlier initiation of androgen deprivation for patients with regional or distant metastases will improve the patient's course. Finally, attempts to provide a more complete androgen blockade hold the hope of delaying or preventing relapse, which usually occurs with continued androgen deprivation.

Topics: Androgen Antagonists; Cyproterone; Cyproterone Acetate; Flutamide; Humans; Male; Megestrol; Megestrol Acetate; Neoplasm Metastasis; Orchiectomy; Pituitary Hormone-Releasing Hormones; Prostatic Neoplasms

Ten male patients with advanced cancer of the breast were treated with cyproterone acetate, an anti-androgenic compound with additional progestational properties. Seven patients achieved a response, for a median duration of 8 months. Plasma testosterone and estradiol levels fell significantly during therapy, but quantitatively this drop was not related to the therapeutic response. Cyproterone acetate is an effective and well-tolerated treatment for metastatic male breast cancer.

Topics: Aged; Breast Neoplasms; Cyproterone; Drug Evaluation; Erectile Dysfunction; Estradiol; Humans; Male; Middle Aged; Neoplasm Metastasis; Prolactin; Testosterone

Topics: Animals; Castration; Combined Modality Therapy; Cyclophosphamide; Cyproterone; Dihydrotestosterone; Male; Neoplasm Metastasis; Prostatic Neoplasms; Rats; Testosterone

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 treatment of early stage prostatic cancer with retropubic radical prostatectomy, pelvic lymphadenectomy and antiandrogenic therapy is reported. Out of 22 patients operated in the past 9 years, none died because of the tumor and metastases appeared in 1 patient only. The latter showed a microscopic seminal vesicle invasion and was considered as a P3 stage. Excluding impotence which is generally the rule, urinary incontinence was the most common complication: it was complete in 1 case but successfully treated surgically and mild in 6 cases without, however, requiring surgical intervention or collection device.

Topics: Aged; Cyproterone; Cyproterone Acetate; Humans; Male; Middle Aged; Neoplasm Metastasis; Prostatic Neoplasms

We have studied 38 patients with previously untreated, widespread prostatic cancer, who were submitted to therapy with cyproterone acetate and orchiectomy. 70% of patients with symptoms have shown subjective improvement. Moreover, it was possible to observe the regression, stabilization or progression of metastases in 32, 50 and 18% of the cases, respectively. We conclude that such therapy is effective in the initial treatment of metastatic prostate cancer and can be continued under radiographic control until the appearance of new metastases. At this point radiotherapy and alkylating agents may be effective.

Topics: Adult; Aged; Carcinoma; Castration; Cyproterone; Humans; Male; Middle Aged; Neoplasm Metastasis; Prognosis; Prostatic Neoplasms; Radiography

Early stage carcinoma of the prostate is curable. Not every patient must be treated because there are significant differences in the biologic activity of the tumors. This causes a sharp difference between morbidity and mortality rate in prostatic cancer. Besides the clinical staging morphological malignancy grading is the trend factor for the treatment that has to be chosen because it has shown to be a reasonable and feasable prognostic indicator.

Topics: Adrenalectomy; Androgen Antagonists; Antineoplastic Agents; Cordotomy; Cyproterone; Estrogens; Humans; Hypophysectomy; Lymph Node Excision; Male; Neoplasm Metastasis; Neoplasm Staging; Palliative Care; Pelvis; Prognosis; Prostatectomy; Prostatic Neoplasms

Sixteen patients with prostatic carcinoma were treated with 200 mg of Cyproterone acetate daily. No other kind of hormonal treatment was administered. Increasing skeletal metastases were observed in 6 patients, whereas significant reduction of metastases took place in 2 patients. Objective relief of stranguria was observed only in 3 patients. The amount of residual urine increased in 3 patients and was reduced in 5. In about one third of the patients, the prostate gland became smaller and softer. The acidic phosphatases decreased from pathological to normal values in 7 patients. There were no observed hepatic, renal or haemotological side-effects. However, serious cardio-vascular complications occurred in 6 patients, while arterial hypertension developed in 4. It is suggested that Cyproterone acetate cannot be recommended as the only kind of hormonal treatment of prostatic cancer.

Topics: Acid Phosphatase; Administration, Oral; Aged; Blood Pressure; Bone Neoplasms; Cyproterone; Humans; Male; Middle Aged; Neoplasm Metastasis; Prostatic Neoplasms; Radiography; Radionuclide Imaging; Urination

Topics: Cyproterone; Humans; Male; Middle Aged; Neoplasm Metastasis; Penile Neoplasms; Prostatic Neoplasms

Topics: Adrenal Gland Neoplasms; Aged; Cyproterone; Female; Hirsutism; Humans; Hysterectomy; Neoplasm Metastasis; Ovarian Neoplasms; Virilism

Topics: Acid Phosphatase; Adult; Aged; Alkaline Phosphatase; Androgen Antagonists; Bone Neoplasms; Carcinoma; Cyproterone; Estrogens; Humans; Liver Neoplasms; Lung Neoplasms; Male; Middle Aged; Neoplasm Metastasis; Pregnadienes; Prostatic Neoplasms

Topics: Bone Neoplasms; Castration; Cyproterone; Estrogens; Humans; Lung Neoplasms; Lymphatic Metastasis; Male; Neoplasm Metastasis; Prostatic Neoplasms; Spinal Cord Neoplasms